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1.
Acta Pharmaceutica Sinica ; (12): 178-187, 2022.
Article in Chinese | WPRIM | ID: wpr-913162

ABSTRACT

Blocking immune checkpoint programmed cell death receptor 1 (PD-1) or programmed death receptor-ligand 1 (PD-L1) can enhance anti-tumor activity of effector T cells. However, the lack of response in many patients to PD-1/PD-L1 therapy remains a question. Improving the immunosuppressive tumor microenvironment (TME) to enhance the efficacy of immune checkpoint inhibitors has become a promising cancer treatment strategy. We constructed a liposome system (PD-L1/siCXCL12-Lp) of CXCL12 siRNA and anti-PD-L1 peptide with matrix metalloproteinases (MMPs) responsiveness, which combined the TME regulation of siCXCL12 and the immune regulation of anti-PD-L1 peptide. All animal experiments were approved by the Biomedical Ethics Committee of Peking University. The authors found that PD-L1/siCXCL12-Lp directly down-regulated the expression of CXCL12 in vitro (33.8%) and in vivo (15.5%). It also effectively increased the ratio of CD8+/Treg by 20.0%, which helped the anti-PD-L1 peptide to better exert its immune effect. The combination therapy significantly inhibited tumor growth (52.08%) with great safety, which explored a new idea for cancer immunotherapy.

2.
Acta Pharmaceutica Sinica ; (12): 802-808, 2022.
Article in Chinese | WPRIM | ID: wpr-922904

ABSTRACT

A blood-brain barrier microfluidic chip platform for studying the permeability of active components in traditional Chinese medicine was developed. This model used primary human brain microvascular endothelial cells on a microfluidic chip consisting of two perpendicularly-crossing channels and a single layer porous polycarbonate membrane. The physiological shear stress in the human vasculature was also modeled in this device. Cell viability on the chip was monitored by cell staining and immunofluorescence staining. The cells spread well and the structure of an intercellular adhesion protein was satisfactory. The permeability of fluorescent tracers and three model drugs and the functional expression of P-glycoprotein (P-gp)on the blood-brain barrier were investigated. The results show that the apparent permeability coefficients (Papp) of the fluorescent tracers and three model drugs were consistent with those reported in the literature, and P-gp on the chip showed normal function, indicating that there was a complete structure and a functional BBB. The permeability of six active components of traditional Chinese medicine was investigated through this microfluidic chip and the drug concentration was determined by HPLC-MS/MS to obtain the Papp of each component. The Papp of corydaline was (4.51 ± 1.90)×10-7 cm·s-1, the Papp of tetrahydropalmatine was (9.10 ± 6.59)×10-7 cm·s-1, and the Papp of imperatorin was (9.38 ± 2.53)×10-7 cm·s-1; the concentration of isoimperatorin, baicalin and chlorogenic acid was below the limit of quantification, which suggested that isoimperatorin, baicalin and chlorogenic acid have poor permeability in this BBB chip. This blood-brain barrier microfluidic platform possesses a complete barrier function and near-physiological conditions and could be a valuable in vitro tool for drug permeability evaluation.

3.
Chinese Journal of Urology ; (12): 830-833, 2021.
Article in Chinese | WPRIM | ID: wpr-911128

ABSTRACT

Objective:To evaluate the feasibility and clinical efficiency of robot-assisted laparoscopic radical prostatectomy (RARP) via extraperitoneal PORT-free single incision approach.Methods:The data of 33 patients with prostate cancer underwent the extraperitoneal PORT-free single incision RARP from November 2020 to January 2021 in Sichuan Provincial People's Hospital was retrospectively reviewed. The average age was 66.7 (58-78) years, the median PSA was 20.77 (2.89, 56.44) ng/m, and the mean Gleason score was 7.0 (6.0-9.0). The mean prostate volume was 48.4 (25.0-220.0) ml. Clinical stage: 32 cases was in cT 2a-2cN 0M 0, 1 case in cT 3aN 0M 0. 16 cases had a history of operation. All 33 operations were performed by the same operator. All operations were performed by extraperitoneal PORT-free single-incision approach. The surgical condition, postoperative complication, pathology, and follow-up results were observed. Results:In this study, 33 operations were successfully completed without conversion to open or additional single hole channel instruments. The average operation time was 61.3 (38.0-120.0) min, with the mean intraoperative bleeding volume of 72.2 (45.0-220.0) ml and the mean bladder neck urethral anastomosis time of 11.7 (8.5-15.7) min. The mean postoperative hospital stay was 7.9 (6.0-15.0) d, the mean postoperative indwelling time of urinary catheter was 6.8 (6.0-14.0) d, and the mean postoperative evacuation time was 1.0 (0.5-3.0) d. The average incision length was 5.2 (4.6-5.8) cm. There was no obvious complications. The postoperative pathological stage: 21 cases were in < pT 3a, 12 cases were in ≥ pT 3a, and 6 cases (18.8%) had positive resection margin. 29 cases (88.9%) acquired satisfactory urinary continence after operation, and the frequency of urinary pad use was ≤ 1 tablet/day. Conclusions:The extraperitoneal single-incision RARP surgical channel without PORT is safe and feasible with a satisfying cosmetic effect, which saves costs and requires less specific channel device. Simultaneously, the new approach has strong replicability, short-term tumor control and urinary control effect with rapid postoperative recovery. However, the sample size of this study is relatively small, which needs further research and demonstration

4.
Article in Chinese | WPRIM | ID: wpr-909597

ABSTRACT

OBJECTIVE To evaluate the effects of flavonoids from Xindakang (Hippophae Fructus flavone) on myo?cardial systolic and diastolic functions of isolated frog hearts and explore the possible mechanism, and provide experi?mental basis for improving the effect and efficacy of Xindakang on cardiac function. METHODS The isolated frog heart perfusion specimens were prepared by Yagi's method, and the effects of different concentrations of Xindakang on myo?cardial contractility (0.0125, 0.025, 0.05, 0.1 and 0.2 g·L-1), heart rate and cardiac output of isolated frog heart were stud?ied. Acetylcholine, atropine and epinephrine were administered successively to analyze the effects of Xindakang on car?diac systolic function of isolated frogs under the action of different drugs, and compared with propranolol. The effect of extracellular calcium ion concentration on the action of Xindakang was studied by using low calcium concentration, high cal?cium concentration and normal Ren's solution. To study the effect and possible mechanism of Xindakang on cardiac systolic function of frog. RESULTS The concentration of Xindakang in the range of 0.0125-0.1 g·L-1 could weaken the contractility of isolated frog heart and increase the concentration of Xindakang. The inhibitory effect of Xindakang on con?tractility of isolated frog heart was enhanced, and showed obvious dose-effect relationship. Cardiac output was signifi?cantly decreased by Xindakang (P<0.01), slow heart rate (P<0.05); M receptor blocker atropine could not antagonize the contractile effect of Xindakang, and Xindakang could not completely antagonize the contractile effect of adrenalin. Xindakang could inhibit the isolated frog heart in low calcium concentration, high calcium concentration and normal Ren's solution, and increased with the increase of extracellular calcium concentration (P<0.01). CONCLUSION Xinda?kang has inhibitory effect on isolated frog heart, which may be achieved by blocking the calcium channel on myocardial cell membrane and reducing the calcium concentration in myocardial cells.

5.
Acta Pharmaceutica Sinica ; (12): 3484-3492, 2021.
Article in Chinese | WPRIM | ID: wpr-906828

ABSTRACT

Compound reserpine and triamterene tablets (CRTT), a compound antihypertensive drug developed by Chinese scientists, is still widely used in clinical practice. However, the mechanisms by which CRTT treats hypertension remain to be fully understood. This study used network pharmacology to analyze CRTT's antihypertensive mechanisms with in vitro experiments. The targets of the four chemical components of CRTT were collected from the Swiss Target Prediction database; 1 828 protein targets related to hypertension were collected from the Therapeutic Target Database (TTD) and Online Mendelian Inheritance in Man (OMIM) database. The CRTT-hypertension network model was constructed using a search tool for recurring instances of neighbouring genes (STRING). Gene ontology (GO) and pathway enrichment analysis of targets of interest was conducted with the Metascape database. In the in vitro study, human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC) were treated with 1 μmol·L-1 angiotensin Ⅱ (AngⅡ) and CRTT was administered at concentrations of 0.01, 0.1, and 1 μmol·L-1. Changes in the phosphatidylinositol-3-kinase/protein serine threonine kinase/endothelial nitric oxide synthase (PI3K/Akt/eNOS) pathway in HUVEC and the cyclic guanosine monophosphate/cGMP-dependent protein kinase (cGMP/PKG) pathway in VSMC were determined by Western blot. Network pharmacological analysis revealed that the antihypertensive effect of CRTT is closely associated with biological pathways such as vascular tone regulation, adrenergic receptor activation, protein kinase activity and signaling pathways such as the cGMP/PKG signaling pathway, vascular smooth muscle contraction, neuroactive ligand-receptor interaction, adrenergic signaling in cardiomyocytes and calcium signaling pathways. The in vitro study confirmed that CRTT increased the levels of phosphorylated phosphatidylinositol-3-kinase (p-PI3K), phosphorylated protein serine threonine kinase (p-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS) in HUVEC and the levels of eNOS, phosphorylated vasodilator-stimulated phosphoprotein (p-VASP), and PKG in VSMC through multiple targets and pathways. These results suggest that the activation of PI3K/Akt/eNOS pathway and endothelial-dependent NO/cGMP signaling may be involved in the CRTT-mediated hypotensive effect.

6.
Article in Chinese | WPRIM | ID: wpr-906400

ABSTRACT

Objective:This study aims to investigate the effect of addition and subtraction treatment to Renshen Maidongsan on metabolism of glucose, lipid and pregnancy outcome when used to gestational diabetes mellitus (GDM) with deficiency of both Qi and Yin. Method:In this study, 108 patients with GDM were randomly divided into observation group with 54 cases and control group with 54 cases. Patients in control group took Yuquan wan orally, 6 g/time, 4 times/day , and patients in observation group were prescribed addition and subtraction treatment to Renshen Maidongsan, 1 dose/day. The course of treatment for both groups was 4 weeks. Oral glucose tolerance test (OGTT) was performed before and after treatment. Fasting blood glucose (FBG) , 1 h our plasma glucose (1 h PG), 2 h our plasma glucose (2 h PG), glycosylated hemoglobin (HbA1c) and other indicators were detected to record the pregnancy outcome. Also, the levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), adiponectin, serum amyloid A (SAA), tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>), resistin, interleukin-1<italic>β</italic> (IL-1<italic>β</italic>) and interleukin-6 (IL-6) were detected before and after treatment. Then the safety evalution was carried out. Result:The levels of insulin resistance index (HOMA-IR), FBG, 1 h PG, 2 h PG, HbA1c, TC, LDL-C, TG, IL-6, IL-1<italic>β</italic>, TNF-<italic>α</italic>, SAA, leptin and resistin in observation group were lower than the data checked in control group (<italic>P</italic><0.01), and the levels of HOMA-<italic>β</italic>, insulin sensitivity index (InISI) and adiponectin were higher than the standards of from control group (<italic>P</italic><0.01). Then the incidence of medical cesarean section, pregnancy induced hypertension, polyhydramnios, premature rupture of membranes, premature delivery and adverse pregnancy outcomes were lower than those in control group (<italic>P</italic><0.01). Conclusion:Addition and subtraction treatment to Renshen Maidongsan can improve insulin sensitivity and islet <italic>β</italic>-cell function, regulate inflammatory factors and adipokines, improve insulin resistance (IR), effectively regulate glucose and lipid metabolism, improve maternal and infant adverse pregnancy outcomes when used on patients with GDM and deficiency of Qi and Yin, and it was safe to use in clinic.

7.
Article in Chinese | WPRIM | ID: wpr-906205

ABSTRACT

Objective:To investigate the effect of notoginseng total saponins (TNS) on adriamycin (Adr) resistance in HepG2/Adr cells and the expression and activity of the mechanisms as the modulators of multi-drug resistance, so as to explore the possible mechanism of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) signaling pathways in reversing the resistance of HepG2/Adr cells mechanism. Method:Effect of TNS on HepG2/Adr cell proliferation was detected by thiazole blue (MTT) method. HepG2/Adr cells were treated with different concentrations (100, 50, 25, 0 mg·L<sup>-1</sup>) of TNS and (20 μmol·L<sup>-1</sup>) Adr respectively, and a blank group was set. The high-content screening platform was used to detect the accumulation of Adr in HepG2/Adr cells after 40 minutes, 3 hours and 6 hours. Western blot was used to detect the expression of P-glycoprotein /multidrug resistance/ATP binding cassette subfamily B member 1(P-gp/MDR1/ABCB1) and other drug resistance-related proteins and the main protein expression of ERK/Akt signaling pathway. The change of MDR1 on cell membranes was observed by laser confocal microscopy. Result:Compared with HepG2 cells, the expression of MDR1 in HepG2/Adr cells was significantly increased (<italic>P</italic><0.01). Compared with the Adr group, the half-inhibitory concentration (IC<sub>50</sub>) of TNS (25, 50, 100 mg·L<sup>-1</sup>) and Adr (20 μmol·L<sup>-1</sup>) co-administration group on HepG2/Adr cells <italic>in vitro</italic> significantly reduced (<italic>P</italic><0.01), and the highest reversal multiple was 10 times. Compared with the Adr group, the co-administration group could significantly increase the accumulation of Adr in the cells (<italic>P</italic><0.05) in a dose-dependent manner. Compared with the blank group, the co-administration group could significantly reduce MDR1, ABC semitransporter (ABCG2), multidrug resistance associated protein (MRP1), ERK, phosphorylated extracellular regulatory protein kinase (p-ERK), Akt, phosphorylated protein kinase B (p-Akt), mammals, rapamycin target protein (mTOR) and phosphorylated mammalian rapamycin target protein (p-mTOR) (<italic>P</italic><0.05), with the same results in the doxorubicin group. Compared with the blank group, there was no significant difference in the distribution and fluorescence intensity of MDR1 on the cell membrane between the Adr group and the notoginseng total saponins (25 mg·L<sup>-1</sup>) group. Compared with the blank group and the doxorubicin group, TNS could significantly reduce the distribution of MDR1 on the cell membrane (<italic>P</italic><0.05). Conclusion:TNS can inhibit the ERK/Akt pathway, reduce the expression of MDR1, and significantly increase the accumulation of doxorubicin in HepG2/Adr cells, which may be one of the mechanisms of notoginseng total saponins in reversing resistance.

8.
Article in Chinese | WPRIM | ID: wpr-906074

ABSTRACT

Objective:To explore the effect and mechanism of Xiangshenwan on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice based on the classic Toll-like receptor (TLR)/nuclear factor kappa B (NF-<italic>κ</italic>B) signaling pathway. Method:The experimental mice were divided into a normal group, a model group, a Xiangshenwan group, and a mesalazine group. The mice, except for those in the normal group, received 3% DSS solution for 7 days to establish the acute UC model and were treated with Xiangshenwan (5 g·kg<sup>-1</sup>) and mesalazine (300 mg·kg<sup>-1</sup>) continuously from the 1st day to the 10th day of modeling. The body weight, disease activity index (DAI), colon weight, intestinal weight index, colon length, colon weight per unit length, and pathological changes of mice were evaluated respectively. The protein expression of TLR5, myeloid differentiation factor 88 (MyD88), interleukin-1 receptor-associated kinase 4 (IRAK4), tumor necrosis factor receptor-associated factor 6 (TRAF6), transforming growth factor <italic>β</italic>-activated kinase 1 (TAK1), p38 mitogen-activated protein kinase (MAPK), NF-<italic>κ</italic>B, IRAK1, TAK1-binding protein 1 (TAB1), TAB2, mitogen-activated protein kinase kinase 3 (MKK3), MKK6 and cyclic adenosine monophosphate response element-binding protein (CREB) in colon tissues of mice was detected by Western blot. Result:Compared with the normal group, the model group showed decreased body weight of mice, increased DAI scores, elevated colon weight, intestinal weight index, and colon weight per unit length, shortened colon length, severe colonic mucosal injury, and up-regulated protein expression of TLR5, MyD88, IRAK4, TRAF6, TAK1, p38 MAPK, NF-<italic>κ</italic>B, IRAK1, TAB1, TAB2, MKK3, MKK6, and CREB in colon tissues (<italic>P</italic><0.05,<italic> P</italic><0.01<bold>).</bold> Compared with the model group, the Xiangshenwan group and the mesalazine group displayed increased body weight of mice, decreased DAI scores, declining colon weight, intestinal weight index, and colon weight per unit length, increased colon length, improved colonic mucosal injury, and down-regulated protein expression of TLR5, MyD88, IRAK4, TRAF6, TAK1, p38 MAPK, NF-<italic>κ</italic>B, IRAK1, TAB1, TAB2, MKK3, MKK6, and CREB in colon tissues (<italic>P</italic><0.05,<italic> P</italic><0.01). Conclusion:Xiangshenwan can effectively treat DSS-induced UC presumedly by the inhibition of TLR/NF-<italic>κ</italic>B signaling pathway.

9.
Article in English | WPRIM | ID: wpr-901446

ABSTRACT

Background@#Pseudorabies virus (PRV) infection leads to high mortality in swine. Despite extensive efforts, effective treatments against PRV infection are limited. Furthermore, the inflammatory response induced by PRV strain GXLB-2013 is unclear. @*Objectives@#Our study aimed to investigate the inflammatory response induced by PRV strain GXLB-2013, establish an inflammation model to elucidate the pathogenesis of PRV infection further, and develop effective drugs against PRV infection. @*Methods@#Kunming mice were infected intramuscularly with medium, LPS, and different doses of PRV-GXLB-2013. Viral spread and histopathological damage to brain, spleen, and lung were determined at 7 days post-infection (dpi). Immune organ indices, levels of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines, as well as levels of activity of COX-2 and iNOS were determined at 4, 7, and 14 dpi. @*Results@#At 105 –106 TCID50 PRV produced obviously neurological symptoms and 100% mortality in mice. Viral antigens were detectable in kidney, heart, lung, liver, spleen, and brain. In addition, inflammatory injuries were apparent in brain, spleen, and lung of PRVinfected mice. Moreover, PRV induced increases in immune organ indices, ROS and NO levels, activity of COX-2 and iNOS, and the content of key pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon-γ and MCP-1. Among the tested doses, 10 2 TCID 50 of PRV produced a significant inflammatory mediator increase. @*Conclusions@#An inflammatory model induced by PRV infection was established in mice, and 102 TCID50 PRV was considered as the best concentration for the establishment of the model.

10.
Article in English | WPRIM | ID: wpr-893742

ABSTRACT

Background@#Pseudorabies virus (PRV) infection leads to high mortality in swine. Despite extensive efforts, effective treatments against PRV infection are limited. Furthermore, the inflammatory response induced by PRV strain GXLB-2013 is unclear. @*Objectives@#Our study aimed to investigate the inflammatory response induced by PRV strain GXLB-2013, establish an inflammation model to elucidate the pathogenesis of PRV infection further, and develop effective drugs against PRV infection. @*Methods@#Kunming mice were infected intramuscularly with medium, LPS, and different doses of PRV-GXLB-2013. Viral spread and histopathological damage to brain, spleen, and lung were determined at 7 days post-infection (dpi). Immune organ indices, levels of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines, as well as levels of activity of COX-2 and iNOS were determined at 4, 7, and 14 dpi. @*Results@#At 105 –106 TCID50 PRV produced obviously neurological symptoms and 100% mortality in mice. Viral antigens were detectable in kidney, heart, lung, liver, spleen, and brain. In addition, inflammatory injuries were apparent in brain, spleen, and lung of PRVinfected mice. Moreover, PRV induced increases in immune organ indices, ROS and NO levels, activity of COX-2 and iNOS, and the content of key pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon-γ and MCP-1. Among the tested doses, 10 2 TCID 50 of PRV produced a significant inflammatory mediator increase. @*Conclusions@#An inflammatory model induced by PRV infection was established in mice, and 102 TCID50 PRV was considered as the best concentration for the establishment of the model.

11.
Acta Physiologica Sinica ; (6): 795-804, 2021.
Article in English | WPRIM | ID: wpr-921282

ABSTRACT

Farnesoid X receptor (FXR) has been identified as an inhibitor of platelet function and an inducer of fibrinogen protein complex. However, the regulatory mechanism of FXR in hemostatic system remains incompletely understood. In this study, we aimed to investigate the functions of FXR in regulating antithrombin III (AT III). C57BL/6 mice and FXR knockout (FXR KO) mice were treated with or without GW4064 (30 mg/kg per day). FXR activation significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), lowered activity of activated factor X (FXa) and concentrations of thrombin-antithrombin complex (TAT) and activated factor II (FIIa), and increased level of AT III, whereas all of these effects were markedly reversed in FXR KO mice. In vivo, hepatic AT III mRNA and protein expression levels were up-regulated in wild-type mice after FXR activation, but down-regulated in FXR KO mice. In vitro study showed that FXR activation induced, while FXR knockdown inhibited, AT III expression in mouse primary hepatocytes. The luciferase assay and ChIP assay revealed that FXR can bind to the promoter region of AT III gene where FXR activation increased AT III transcription. These results suggest FXR activation inhibits coagulation process via inducing hepatic AT III expression in mice. The present study reveals a new role of FXR in hemostatic homeostasis and indicates that FXR might act as a potential therapeutic target for diseases related to hypercoagulation.


Subject(s)
Animals , Antithrombin III , Blood Coagulation , Hepatocytes , Liver , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, Cytoplasmic and Nuclear/genetics
12.
Article in English | WPRIM | ID: wpr-881045

ABSTRACT

Osteoporosis is a health problem to cause global concern. A lot of methods have been used to prevent and treat osteoporosis, but there is still a lack of effective treatment for osteoporosis owing to limited understanding of its mechanism. Therefore, the aim of this present study is to explore the underlying mechanism of Wuling Powder, a traditional Chinese medicine on treating osteoporosis. In this study, we firstly screened and identified the common targets between Wuling Powder and osteoporosis through the related databases, and then explored the relationships among these targets, Wuling Powder and osteoporosis by using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and network analyses. Subsequently, the molecular docking was performed by using systemsDock to evaluate the potential binding relationships between the active components of Wuling Powder and their related targets. The results showed that in total of 14 common targets including CREBBP, ADAM17, GOT1, GAPDH, USP8, ERBB2, EEF1A1, MTOR, RAC1, ETS1, DDX58, GCK, EGF and S100A8 were screened. EGF, ERBB2, MTOR and HIF-1 were the potential therapeutic targets for osteoporosis, and they were also the related targets for predicting active components in Wuling Powder. Taken together, we concluded that Wuling Powder might be used to treat osteoporosis through above these targets.

13.
Article in Chinese | WPRIM | ID: wpr-886652

ABSTRACT

Objective:To understand the swallowing function of the elderly in welfare homes of Wenzhou City,Zhejiang Province and to analyze the related factors of swallowing dysfunction. Methods:A total of 507 elderly people aged 60 years and over were surveyed by questionnaires in three welfare homes of Wenzhou City from January 2018 to January 2020.Hinds time-limited water drinking test was used to screen dysphagia. Multivariate unconditional logistic regression analysis was used to analyze the related factors of swallowing dysfunction. Results:The incidence of swallowing dysfunction was 26.04% (132 out of 507). Univariate analysis showed that there were significant differences in the incidence of swallowing dysfunction among the elderly in terms of age, spouse condition, self-care ability, health status, taking sleeping pills, cerebrovascular disease, nervous system disease and depression (P<0.05). Multivariate logistic regression analysis showed that the following factors were related to swallowing dysfunction among the elderly: age ≥80 years old, taking sleeping pills, cerebrovascular diseases, nervous system diseases and depression. Conclusion:The incidence of swallowing dysfunction in elderly people in welfare homes of Wenzhou City is high, especially those aged ≥80 years who need more attention. In addition, taking sleeping pills, cerebrovascular diseases, nervous system diseases and depression all increase the risk of swallowing dysfunction. Corresponding preventive and intervention measures should be formulated.

14.
Chinese Journal of Urology ; (12): 116-121, 2021.
Article in Chinese | WPRIM | ID: wpr-884969

ABSTRACT

Objective:To compare the clinical efficacy of transperitoneal robot assisted laparoscopic radical prostatectomy (RARP) versus extraperitoneal single port RARP.Methods:A retrospective analysis was perfoumed on 142 cases of RARP from July 2019 to June 2020 in Robotic Minimally Invasive Center of Sichuan Provincial People's Hospital, including 82 cases(Group A) , aged 70.0(65.6-78.0), undergoing transperitoneal RARP and 60 cases(Group B), aged 68.2 years old(60.1-79.2), undergoing extraperitoneal single port RARP. For group A, PSA was 12.9(5.6-64.0) ng/ml, with 26 cases of less than 10 ng/ml(31.7%), 40 cases of 10-20 ng/ml(48.8%), and 16 cases of more than 20 ng/ml(19.5%), the Gleason score was 7.2(6.0-10.0), with 14 cases(17.1%) of ≤6, 56 cases(68.3%) of 7, and 12 cases(14.6%) of ≥8, and the prostate volume was 61.3(29.0-112.0) ml. There were 49 cases with BMI≤25 kg/m 2, accounting for 59.8%, and 33 cases with BMI>25 kg/m 2, accounting for 40.2%. There were 17 cases(20.7%) of T 1, 44 cases(53.7%) of T 2 and 21 cases(25.6%) of T 3. The proportion of lymph node dissection was 17.1%, and 4 cases(4.9%)had a history of operation. For group B, the PSA was 12.2(1.0-42.6)ng/ml, with 20 cases (33.3%) of <10 ng/ml, 31 cases(51.7%)of 10-20 ng/ml, and 9 cases (15%) of >20 ng/ml. Gleason score was 7.1(6.0-9.0), with 12 cases (20.0%) of ≤6, 42 cases (70.0%) of 7, and 6 cases (10.0%)of ≥8. Prostate volume was 42.4(31.2-72.8)ml on average. There were 37 cases (61.7%) with BMI≤25 kg/m 2, and 23 cases (38.3%)with BMI >25 kg/m 2 . There were 17 cases(28.3%)of T 1, 32 cases(53.3%)of T 2 and 11 cases(18.3%)of T 3.The proportion of lymph node dissection was 11.7% and 4 cases (6.7%) had a history of operation.There was no statistically significant difference in term of age, PSA level, Gleason score, BMI, clinical stage, proportion of lymph node dissection or history of operation between the two groups( P>0.05), but there was statistically significant difference for prostate volume( P<0.05). All operations were performed by the same operator. Four different ways of bladder neck and urethral dissociation was selected according to the intraoperative conditions in Group A, include VIP style, T-shape incision style, VIP plus T-shape incision style or the style along the lateral side of the bladder neck. Small and single anterograde incision stripping of bladder neck was routinely performed in the Group B. Postoperative follow-up was performed to compare the operation time, intraoperative blood loss, bladder neck and urethral anastomosis time, postoperative hospital stay, postoperative exhaust time, postoperative complications, positive rate of surgical margin, indwelling time of urinary catheter, urinary continence satisfaction rate of immediately after operation, 3 months and 6 months after operation, wound healing and aesthetics. Results:All of the operations were successfully completed under robot-assisted laparoscopy, and there was no conversion to open surgery. The operation time was 56.0(45.0-112.0) min in the Group A and 65.4(55.5-96.8) min in the Group B, and there was no statistically significant difference( P>0.05). The intraoperative blood loss was 76.2(30.0-120.5) ml and 55.6(45.5-114.6) ml, respectively, and the difference was not statistically significant( P>0.05). The time of bladder neck urethral anastomosis was 18.9(12.6-25.6) min and 16.2(10.7-19.3) min, respectively, and the difference was not statistically significant( P>0.05). The postoperative hospital stay days were 9.3(8.0-16.0) d and 8.4(7.0-13.0) d, respectively, and the difference was not statistically significant( P>0.05). The postoperative exhaust time was 1.3(0.7-3.0) d and 3.4(2.0-7.0) d, respectively, and the difference was statistically significant( P<0.05). There was 1 case of anastomotic fistula with ureteral injury in Group A, and no serious complication in Group B, and the difference was not statistically significant( P>0.05). The number of positive surgical margin in the two groups was 13(15.9%)and 9(15.0%)respectively, and the difference was not statistically significant( P>0.05). The indwelling time of urinary catheter after operation was 9(7-21) d and 6(4-8) d, respectively, and the difference was statistically significant( P<0.05). The number of patients with satisfactory urinary continence immediately after surgery, 3 months and 6 months after surgery in the two groups were 8(9.8%), 51(62.2%), 62(75.6%) and 17(28.3%), 43(71.7%) and 54(90.0%), respectively. The differences were statistically significant( P<0.05). The total incision lengths in the two groups were 12.1(10.4-13.4) cm and 5.6(5.0-6.0) cm, respectively, and the difference was statistically significant( P<0.05). Conclusions:The extraperitoneal single port RARP is safe and feasible, and the postoperative effect is similar to that of transperitoneal RARP. It has the advantages of shorter recovery time, higher urinary continence satisfaction rate, neater and more beautiful incision. The long-term therapeutic effect needs further confirming by prospective study.

15.
Article in Chinese | WPRIM | ID: wpr-879824

ABSTRACT

OBJECTIVE@#To study the clinical features of children with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, a polygenic and multifactorial autoinflammatory disease with unknown pathogenesis.@*METHODS@#A retrospective analysis was performed on the medical data of 13 children with PFAPA syndrome.@*RESULTS@#All 13 children had disease onset within the age of 3 years, with a mean age of onset of (14±10) months. They all had periodic fever, with 8-18 attacks each year. The mean interictal period of fever was (30±5) days. Pharyngitis, cervical adenitis, and aphthous stomatitis were the three cardinal symptoms, with incidence rates of 100% (13/13), 85% (11/13), and 38% (5/13) respectively. There were increases in white blood cells, C-reactive protein, and erythrocyte sedimentation rate during fever. Of all the 13 children, 6 underwent whole exome sequencing and 7 underwent panel gene detection for autoinflammatory disease, and the results showed single heterozygous mutations in the @*CONCLUSIONS@#For children with unexplained periodic fever with early onset accompanied by pharyngitis, cervical adenitis, aphthous stomatitis, elevated inflammatory indices, and good response to glucocorticoids, PFAPA syndrome should be considered. This disorder has good prognosis, and early diagnosis can avoid the long-term repeated use of antibiotics.


Subject(s)
Child , Child, Preschool , Fever/etiology , Humans , Infant , Lymphadenitis/diagnosis , Pharyngitis/drug therapy , Pyrin , Retrospective Studies , Stomatitis, Aphthous/genetics
16.
Article | WPRIM | ID: wpr-833693

ABSTRACT

Background@#Panax notoginseng saponins (PNS) are bioactive substances extracted from P. notoginseng that are widely used to treat cardiovascular and cerebrovascular diseases and interstitial diseases. PNS have the functions of scavenging free radicals, anti-inflammation, improving blood supply for tissue and so on. @*Objectives@#The aim of this study was to investigate the effects of PNS on the oxidative stress of immune cells induced by porcine circovirus 2 (PCV2) infection in vitro and in vivo. @*Methods@#Using an oxidative stress model of PCV2 infection in a porcine lung cell line (3D4/2 cells) and mice, the levels of nitric oxide (NO), reactive oxygen species (ROS), total glutathione (T-GSH), reduced glutathione (GSH), and oxidized glutathione (GSSG) and the activities of xanthine oxidase (XOD), myeloperoxidase (MPO) and inducible nitric oxide synthetase (iNOS) were determined to evaluate the regulatory effects of PNS on oxidative stress. @*Results@#PNS treatment significantly reduced the levels of NO and ROS, the content of GSSG and the activities of XOD, MPO, and iNOS (p < 0.05), while significantly increasing GSH and the ratio of GSH/GSSG in infected 3D4/2 cells (p < 0.05).Similarly, in the in vivo study, PNS treatment significantly decreased the level of ROS in spleen lymphocytes of infected mice (p < 0.05), increased the levels of GSH and T-GSH (p < 0.05), significantly decreased the GSSG level (p < 0.05), and decreased the activities of XOD, MPO, and iNOS. @*Conclusions@#PNS could regulate the oxidative stress of immune cells induced by PCV2 infection in vitro and in vivo.

17.
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.

18.
Article in Chinese | WPRIM | ID: wpr-872935

ABSTRACT

Objective:To study the mechanism of Shengmaisan in treating atrial fibrillation by regulating relative genes and signaling pathways based on network pharmacology. Method:Target genes of Shengmaisan were obtained using Bioinformatics Analysis Tool for Molecular Mechanism of TCM(BATMAN-TCM) database,and target genes of atrial fibrillation were obtained through GeneCards,OMIM and DisGeNET databases. The target genes of Shengmaisan-atrial fibrillation intersection protein were obtained through the integration of the two groups of genes. STRING was used to build the protein-protein interaction network and visualize the results. The drug-disease intersection genes were introduced into the DAVID 6.8 database for gene ontology (GO) analysis and enrichment analysis based on the Kyoto Encyclopedia of Genes and Geomes (KEGG). Result:A total of 159 active ingredients for Shengmai powder for atrial fibrillation were obtained. After the drug targets and the disease targets were intersected,206 common targets were obtained. PPI protein interaction network analysis showed that AKT1,TP53,PRKACA,IL-1B,TNF,INS,PPAR,RXR,F2,CACAN1C PKC might be the core targets of Shengmaisan in treating AF. GO enrichment analysis was used to identify 175 items (P<0.05),among which biological processes mainly included regulation of heart rate by cardiac conduction,membrane depolarization during action potential;cell components mainly included voltage-gated sodium/ potassium/calcium channel complex;molecular functions mainly included high-voltage-gated calcium channel activity,steroid hormone receptor activity. Through KEGG pathway enrichment analysis,100 signaling pathways were identified,mainly including cGMP/PKG signaling pathway,cAMP signaling pathway,serotonergic synapse,renin secretion,calcium signaling pathway. Conclusion:Based on the network pharmacology,Shengmaisan has multiple mechanisms in the prevention and treatment of atrial fibrillation. This study explores relevant signaling pathways,advantages and research directions of Shengmaisan in treatment of atrial fibrillation,so as to lay the foundation for further experimental verification.

19.
Article in Chinese | WPRIM | ID: wpr-872403

ABSTRACT

In consideration of the current policies for scientific and technological achievement translation, the paper explored the model and strategy of such translation in medical institutions by analyzing typical cases of " orthopedic surgical robot" translation. Most common translation models in medical institutions are transfer or licensing. As hospitals lack the qualifications and conditions for product manufacturing and sales, " orthopedic surgical robot" was translated by means of a combined practice of both patent transfer and joint R&D with the enterprise under a strategic cooperation agreement. This practice not only manifested the contribution and interests of stakeholders in a rational way, but also guaranteed sustainable iterative R&D. Hospitals should launch cooperation with enterprises, universities or research organizations and form strategic alliances, and choose appropriate translation models based on their specifics, value and characteristics of the achievement flexibly.

20.
Acta Pharmaceutica Sinica ; (12): 1801-1811, 2020.
Article in Chinese | WPRIM | ID: wpr-825154

ABSTRACT

This study systematically investigated the therapeutic effects of chemotherapy-induced mucositis (CIM) by cryptotanshinone (CTS) in mice. CIM mice were prepared by intraperitoneal injection of 5-fluorouracil (5-FU) and irinotecan for 4 days. A pseudo-sterile mouse model was established by intragastric administration of mixed antibiotics (metronidazole, vancomycin, and penicillin). The body weight, disease activity index (DAI), and defecation of mice were daily monitored. The animal welfare and experimental procedures followed the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. We determined the contents of inflammatory factors, total cholesterol (TC), triglyceride (TG), and lipase activity in serum or colonic mucosa of CIM mice. We also studied the composition and relative abundance of fecal flora. The correlation of the relative abundance of fecal microbiota and environmental factors was further analyzed. CTS significantly decreased DAI and reduced the content of interleukin 6 (IL-6), interleukin 11 (IL-11), myeloperoxidase (MPO), and diamine oxidase (DAO) in the serum of CIM mice. CTS effectively increased the content of TG while reduced TC and lipase activity in serum. Results showed the incidence of CIM in pseudoaseptic model group was significantly reduced. Meanwhile, there was no significant difference in the contents of inflammatory factors and TG/TC ratio between pseudoaseptic model group and normal control group. There was a significant difference in the diversity and composition of fecal microbiota among groups. In addition, CTS restored the composition of fecal microbiota close to normal and significantly increased the abundance of g_norank_f_Muribaculaceae. Especially, g_Ruminiclostridium and g_norank_f_Muribaculaceae exhibited a significant positive correlation to TG but a negative correlation to DAO, MPO, IL-6, lipase, and TC. Cryptotanshinone significantly increased the abundance of g_norank_f_Muribaculaceae and g_ruminococcaceae_UCG-014 in fecal microbiota of CIM mice. In conclusion, we reported CTS effectively alleviated intestinal mucositis in mice induced by 5-fluorouracil and irinotecan by regulating fecal microbiota, inflammatory factors, and serum lipid.

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