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1.
Chinese Journal of Cardiology ; (12): 690-697, 2022.
Article in Chinese | WPRIM | ID: wpr-940908

ABSTRACT

Objective: To investigate the effect and mechanism of sacubitril/valsartan on left ventricular remodeling and cardiac function in rats with heart failure. Methods: A total of 46 SPF-grade male Wistar rats weighed 300-350 g were acclimatized to the laboratory for 7 days. Rats were then divided into 4 groups: the heart failure group (n=12, intraperitoneal injection of adriamycin hydrochloride 2.5 mg/kg once a week for 6 consecutive weeks, establishing a model of heart failure); heart failure+sacubitril/valsartan group (treatment group, n=12, intragastric administration with sacubitril/valsartan 1 week before the first injection of adriamycin, at a dose of 60 mg·kg-1·d-1 for 7 weeks); heart failure+sacubitril/valsartan+APJ antagonist F13A group (F13A group, n=12, adriamycin and sacubitril/valsartan, intraperitoneal injection of 100 μg·kg-1·d-1 APJ antagonist F13A for 7 weeks) and control group (n=10, intraperitoneal injection of equal volume of normal saline). One week after the last injection of adriamycin or saline, transthoracic echocardiography was performed to detect the cardiac structure and function, and then the rats were executed, blood and left ventricular specimens were obtained for further analysis. Hematoxylin-eosin staining and Masson trichrome staining were performed to analyze the left ventricular pathological change and myocardial fibrosis. TUNEL staining was performed to detect cardiomyocyte apoptosis. mRNA expression of left ventricular myocardial apelin and APJ was detected by RT-qRCR. ELISA was performed to detect plasma apelin-12 concentration. The protein expression of left ventricular myocardial apelin and APJ was detected by Western blot. Results: Seven rats survived in the heart failure group, 10 in the treatment group, and 8 in the F13A group. Echocardiography showed that the left ventricular end-diastolic diameter (LVEDD) and the left ventricular end-systolic diameter (LVESD) were higher (both P<0.05), while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the heart failure group than in the control group (both P<0.05). Compared with the heart failure group, rats in the treatment group were featured with lower LVEDD and LVESD (both P<0.05), higher LVEF and LVFS (both P<0.05), these beneficial effects were reversed in rats assigned to F13A group (all P<0.05 vs. treatment group). The results of HE staining showed that the cardiomyocytes of rats in the control group were arranged neatly and densely structured, the cardiomyocytes in the heart failure group were arranged in disorder, distorted and the gap between cells was increased, the cardiomyocytes in the treatment group were slightly neat and dense, and cardiomyocytes in the F13A group were featured similarly as the heart failure group. Masson staining showed that there were small amount of collagen fibers in the left ventricular myocardial interstitium of the control group, while left ventricular myocardial fibrosis was significantly increased, and collagen volume fraction (CVF) was significantly higher in the heart failure group than that of the control group (P<0.05). Compared with the heart failure group, the left ventricular myocardial fibrosis and the CVF were reduced in the treatment group (both P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). TUNEL staining showed that the apoptosis index (AI) of cardiomyocytes in rats was higher in the heart failure group compared with the control group (P<0.05), which was reduced in the treatment group (P<0.05 vs. heart failure group), this effect again was reversed in the F13A group (P<0.05 vs. treatment group). The results of RT-qPCR and Western blot showed that the mRNA and protein levels of apelin and APJ in left ventricular myocardial tissue of rats were downregulated in heart failure group (all P<0.05) compared with the control group. Compared with the heart failure group, the mRNA and protein levels of apelin and APJ were upregulated in the treatment group (all P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). ELISA test showed that the plasma apelin concentration of rats was lower in the heart failure group compared with the control group (P<0.05); compared with the heart failure group, the plasma apelin concentration of rats was higher in the treatment group (P<0.05), this effect was reversed in the F13A group (P<0.05 vs. treatment group). Conclusion: Sacubitril/valsartan can partially reverse left ventricular remodeling and improve cardiac function in rats with heart failure through modulating Apelin/APJ pathways.


Subject(s)
Aminobutyrates/pharmacology , Animals , Apelin/metabolism , Biphenyl Compounds , Collagen/metabolism , Doxorubicin/pharmacology , Fibrosis , Heart Failure/pathology , Male , Myocytes, Cardiac/pathology , RNA, Messenger/metabolism , Rats , Rats, Wistar , Valsartan/pharmacology , Ventricular Function, Left/drug effects , Ventricular Remodeling
2.
Article in Chinese | WPRIM | ID: wpr-940395

ABSTRACT

ObjectiveTo explore the pharmacodynamic ingredients of Zhenqi Fuzheng granules (ZFG) for immunomodulatory through spectrum-effect relationship analysis, which provides experimental basis for improving the quality standard of ZFG. MethodEighteen batches of ZFG from six manufacturers were collected for analysis. The fingerprints were established by high performance liquid chromatography (HPLC). Acetonitrile (A)-0.1% formic acid aqueous solution (B) were adopted as the mobile phase with gradient elution (0-15 min, 5%A; 15-23 min, 5%-8%A; 23-30 min, 8%-11%A; 30-45 min, 11%-18%A; 45-60 min, 18%-21%A; 60-67 min, 21%-23%A; 67-90 min, 23%-37%A), the detection wavelength was 220 nm. Chemometric analysis such as similarity analysis and hierarchical cluster analysis (HCA) were subsequently used to analyze the similarities and chemical differences among these samples. A cyclophosphamide-induced immunodeficiency mouse model was used to evaluate the immune-enhancing effects of the products from different manufacturers. The spectrum-effect relationship between HPLC fingerprints and the immunomodulatory effects was examined using Spearman bivariate correlation analysis. HPLC coupled with mass spectrometry (HPLC-MSn) was used to identify the spectrum-effect related peaks with electrospray ionization, positive and negative ion modes, and scanning range of m/z 100-1 500. ResultThe HPLC fingerprint of ZFG was established, and twenty peaks with good resolution were selected as common peaks. The results of quality analysis and pharmacodynamic test showed there were significant differences in both ingredients content and immune-enhancing effects of ZFG from different manufacturers. Through spectrum-effect relationship study, twelve peaks were screened as bioactive ingredients peaks. Thereafter, eight peaks among them were subsequently identified by HPLC-MSn. They were salidroside (peak 2), echinacoside (peak 5), calycosin-7-glucoside (peak 6), isomer of specnuezhenide (peak 7), isonuezhenide (peak 9), calycosin (peak 11), nuezhenide G13 or oleonuezhenide (peak 14), and formononetin (peak 18), respectively. ConclusionThere are differences in quality and efficacy of ZFG produced by different manufacturers. Through spectrum-effect relationship analysis, the medicinal ingredients of ZFG for immune-enhancing effects are screened, which can provide reference for the improvement of its quality standard.

3.
Article in Chinese | WPRIM | ID: wpr-940287

ABSTRACT

ObjectiveTo study the effects of Chinese herbal compound Youguiwan on angiogenesis of rats with ovarian dysfunction caused by natural aging and its relationship with chemokine interleukin 8 (CXCL8)/CXC chemokine receptor 1/2 (CXCR1/2) signaling pathway, angiopoietin 1 (Ang-1), and angiopoietin 2 (Ang-2), so as to explore its mechanism in improving the ovarian function. MethodFifty six female SD rats were randomly divided into the young control group (n=8) and modeling group (n=48, ovarian dysfunction caused by natural aging). Rats in both the young control and modeling groups were routinely fed, during which the ones in the modeling group underwent exfoliative cytology of vaginal smears for five to seven days. The ones presented with prolonged estrous cycle, followed by continuous estrus and repeated pseudopregnancy revealed by vaginal cytology during four consecutive estrous cycles indicated early aging, and the young rats with keratinocyte proliferation index higher than 50% for 10 consecutive days were classified into the young control group. The successfully modeled rats were randomly divided into the early-aged group, estrogen (65 μg·kg-1·d-1) group, Zuoguiwan (33 g·kg-1·d-1) group, as well as the low-, medium-, and high-dose (1.2, 2.4, 4.8 g·kg-1·d-1) Youguiwan groups. Rats in the young control group and the early-aged group were gavaged with the same volume of normal saline for 30 days. After the experiment, the morphological changes in rat ovary were observed by hematoxylin-eosin (HE) staining. The protein expression levels of chemokines CXCL8, CXCR1, CXCR2, Ang-1, and Ang-2 in rat ovary were detected by Western blotting and immunohistochemistry, and the mRNA expression levels of CXCL8, CXCR1, CXCR2, Ang-1, and Ang-2 by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultCompared with the young control group, the early-aged group exhibited reduced number of growing follicles, corpus luteum, and blood vessels at all levels, elevated atretic follicles (P<0.01), up-regulated protein and mRNA expression of CXCL8, CXCR1, and CXCR2 in the ovarian tissue (P<0.01), and down-regulated Ang-1 and Ang-2 protein and mRNA expression (P<0.05). Compared with the early-aged group, each medication remarkably increased the number of growing follicles, corpus luteum, and blood vessels (P<0.05), lowered the number of atretic follicles (P<0.05), down-regulated the protein and mRNA expression levels of CXCL8, CXCR1, and CXCR2 in the ovarian tissue (P<0.05), and up-regulated the protein and mRNA expression levels of Ang-1 and Ang-2 (P<0.05). ConclusionYouguiwan down-regulates the levels of CXCL8, CXCR1, and CXCR2 in rat ovary and up-regulates the levels of Ang-1 and Ang-2 to promote ovarian angiogenesis and improve rat ovarian function.

4.
Chinese Journal of Surgery ; (12): 498-503, 2022.
Article in Chinese | WPRIM | ID: wpr-935626

ABSTRACT

With the popularization of health screening and the widespread use of low-dose computed tomography, the detection rate of lung nodules has increased year after year. However, the false positive rates testified by surgery of these lung nodules are still high. Therefore, it is vital in clinical practice to avoid overtreatment or undertreatment. But a series of problems on how to make an accurate diagnosis, how to reduce the psychological pressure of patients and follow up with regular imaging, how to clarify the indications for surgery and adopt the most minimally invasive diagnosis and treatment methods, etc. remain unsolved. Over the past decade, the diagnostic techniques for pulmonary nodules have improved significantly, including imaging progress such as the optimization of traditional imaging techniques (CT, MRI) and the emergence of new technologies (radiomics, artificial intelligence). In addition, histological improvements including percutaneous transthoracic needle biopsy, bronchoscopy, and minimally invasive surgical biopsy, etc. have brought more reliable and precise options for characterization of pulmonary nodules.


Subject(s)
Artificial Intelligence , Biopsy, Needle/methods , Bronchoscopy , Humans , Lung Neoplasms/diagnosis , Tomography, X-Ray Computed
5.
Chinese Journal of Surgery ; (12): 356-362, 2022.
Article in Chinese | WPRIM | ID: wpr-935611

ABSTRACT

Objectives: To investigate the clinical value of adjuvant chemotherapy(ACT) in patients with intrahepatic cholangiocarcinoma(ICC) who underwent radical resection and to explore the optimal population that can benefit from ACT. Methods: A retrospective cohort study method was adopted. The clinical and pathological data of 685 patients with ICC who underwent curative intent resection in 10 Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected;There were 355 males and 330 females. The age(M(IQR)) was 58(14) years (range: 22 to 83 years). Propensity score matching(PSM) was applied to balance the differences between the adjuvant and non-adjuvant chemotherapy groups. Log-rank test was used to compare the prognosis of the two groups of patients. A Bayesian network recurrence-free survival(RFS) prediction model was constructed using the median RFS time (14 months) as the target variable, and the importance of the relevant prognostic factors was ranked according to the multistate Birnbaum importance calculation. A survival prognostic prediction table was established to analyze the population benefiting from adjuvant chemotherapy. Results: Among 685 patients,214 received ACT and 471 did not receive ACT. A total of 124 pairs of patients were included after PSM, and patients in the ACT group had better overall survival (OS) and RFS than those in the non-ACT group(OS: 32.2 months vs. 18.0 months,P=0.003;RFS:18.0 months vs. 10.0 months,P=0.001). The area under the curve of the Bayesian network RFS prediction model was 0.7124. The results of the prognostic factors in order of importance were microvascular invasion (0.158 2),perineural invasion (0.158 2),N stage (0.155 8),T stage (0.120 9), hepatic envelope invasion (0.090 3),adjuvant chemotherapy (0.072 1), tumor location (0.057 5), age (0.042 3), pathological differentiation (0.034 0), sex (0.029 3), alpha-fetoprotein (0.028 9) and preoperative jaundice (0.008 5). A survival prediction table based on the variables with importance greater than 0.1 (microvascular invasion,perineural invasion,N stage,T staging) and ACT showed that all patients benefited from ACT (increase in the probability of RFS≥14 months from 2.21% to 7.68%), with a more significant increase in the probability of RFS≥14 months after ACT in early-stage patients. Conclusion: ACT after radical resection in patients with ICC significantly prolongs the OS and RFS of patients, and the benefit of ACT is greater in early patients.


Subject(s)
Bayes Theorem , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/pathology , Chemotherapy, Adjuvant , Cholangiocarcinoma/surgery , Female , Humans , Male , Prognosis , Retrospective Studies
6.
Article in Chinese | WPRIM | ID: wpr-935255

ABSTRACT

Exploring a new teaching mode of CHB laboratory diagnostics to improve the teaching quality through establishment a teaching model covered the whole process of CHB disease diagnosis and differential diagnosis, treatment, drug selection, the toxicity and side effects prediction, effect monitoring, and prognosis evaluation. According to the CHB clinical diagnosis and treatment guidelines, formulated the laboratory examination and detection strategies related to different stages of CHB, and established CHB clinical laboratory diagnostic pathway. Compared the classroom teaching effect by the questionnaire between the 2016 and 2017 eight-year undergraduates from the First Clinical College of Wuhan University. In this study,the CHB clinical laboratory diagnostic pathway was established and approved by clinicians, which covered the whole process of CHB disease diagnosis and differential diagnosis, treatment, drug selection, the toxicity and side effects prediction, effect monitoring, and prognosis evaluation. The teaching quality evaluation indicators and the scores on the class test had been greatly improved with the clinical diagnostic pathway teaching mode in the classroom teaching of 2017 clinical medicine undergraduates compared with the traditional teaching mode in the 2016 clinical medicine undergraduates. In summary, the medical students not only could realize the organic integration of laboratory diagnostics and clinical medicine, but also improves overall understanding of various laboratory tests in CHB diagnosis and treatment from the teaching model of laboratory diagnostics based on the CHB clinical laboratory diagnostic pathway,and the quality of teaching for CHB has been significantly improved.


Subject(s)
Clinical Laboratory Techniques , Hepatitis B, Chronic , Humans , Laboratories , Laboratories, Clinical , Records
7.
Chinese Journal of Oncology ; (12): 185-191, 2022.
Article in Chinese | WPRIM | ID: wpr-935200

ABSTRACT

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.


Subject(s)
Carcinoma, Adenoid Cystic/pathology , Humans , Paranasal Sinus Neoplasms/therapy , Prognosis , Proportional Hazards Models , Retrospective Studies
8.
Article in Chinese | WPRIM | ID: wpr-934336

ABSTRACT

Objective:To investigate the diagnostic value of triglyceride/cystatin C (TG/Cys-C) ratio combined with diabetic retinopathy, diabetes course and systolic pressure in patients with diabetic kidney disease (DKD).Methods:Patients with type 2 diabetes and renal insufficiency, who underwent renal biopsy in four Grade A tertiary hospitals in Xuzhou from January 2013 to February 2021 were included in this retrospective study. Patients were divided into DKD group ( n=51) and non-DKD (NDKD) group ( n=49) based on renal biopsy results. Another 50 patients with type 2 diabetes mellitus without renal dysfunction were selected as control group. The first admission information and blood biochemical indexes were collected, and the TG/Cys-C ratio was calculated. The differences of clinical indexes between the DKD and NDKD groups were compared. The correlative factors of DKD in type 2 diabetes patients with renal dysfunction were analyzed by logistic regression. The ROC curve was used to evaluate the diagnostic value of TG/Cys-C ratio, diabetic retinopathy, duration of diabetes, systolic blood pressure and combined detection for DKD in patients with type 2 diabetes and renal dysfunction. Results:Among patients with type 2 diabetes with renal dysfunction, renal biopsy results showed that membranous nephropathy was the most common pathological type in NDKD group, accounting for 63.3% (31/49) of all NDKD patients. Compared with Type 2 diabetes mellitus without renal injury, type 2 diabetic patients with kidney injury had higher systolic blood pressure, higher total cholesterol, higher low-density lipoprotein, higher cystatin, higher creatinine, higher uric acid, higher fibrinogen level, more hypertension, more changes of urinary active sediment, lower hemoglobin, lower albumin, and the lower the glomerular filtration rate (all P<0.05). Compared with NDKD group, patients in DKD group had higher systolic and diastolic blood pressure, higher cystatin C and creatinine, more hypertension, more diabetic retinopathy, longer course of diabetes, lower concentration of hemoglobin, lower glomerular filtration rate, lower triglyceride and lower TG/Cys-C ratio (all P<0.05). Multivariate logistic regression analysis showed that TG/Cys-C ratio was associated with DKD in patients with type 2 diabetes mellitus and renal impairment ( OR=0.298, P=0.007), diabetic retinopathy ( OR=12.209, P=0.005), duration of diabetes ( OR=1.016, P=0.034) and systolic blood pressure ( OR=1.049, P=0.006) were independent risk factors for DKD in type 2 diabetic patients with renal dysfunction. The ROC curve showed that AUC of the TG/Cys-C ratio was 0.866 (the cot-off point was 2.06), and the sensitivity was 88.2% and the specificity was 71.4% for the diagnosis of DKD, and AUC of the TG/Cys-C ratio in combination with diabetic retinopathy, diabetes duration and systolic blood pressure was 0.952, and the sensitivity was 92.2% and the specificity was 89.8% for the diagnosis of DKD. Conclusion:TG/Cys-C ratio has significant clinical value in the diagnosis of DKD. Combined detection of TG/Cys-C ratio with diabetic retinopathy, course of diabetes and systolic blood pressure could further improve the diagnostic efficacy of DKD.

9.
Chinese Journal of Hematology ; (12): 414-419, 2022.
Article in Chinese | WPRIM | ID: wpr-929629

ABSTRACT

Objective: To establish three types of xenotransplantation models using human myeloma cell lines ARP1, MM.1S, and NCI-H929 and to compare the proliferation, tumor load, and biological characteristics of the three types of cells after transplantation. Methods: Suspensions of human myeloma cell lines ARP1, MM.1S, and NCI-H929 were implanted into NOD/SCID mice by subcutaneous injection or tail vein injection. The survival of the mice was observed weekly, and the tumor load was measured. Flow cytometry was used to detect the proportion of CD138(+) cells in tumor tissue or the mouse bone marrow. CD138(+) cells and light chains were detected by immunofluorescence. Light chains in bone marow and peipheral blood were measured by ELISA, and bone disease was assessed by micro-CT. Results: Mice injected with ARP1, MM.1S, and NCI-H929 cells all formed tumors subcutaneously in about 2 weeks. Immunofluorescence detection supported plasma cell tumors. Kappa light chains were detected in the peripheral blood of ARP1 mice on day 20 after tail vein transplantation (8.2±1.0 ng/ml) . After 6 weeks of tail vein transplantation, mice in the ARP1 group showed signs of weight loss, mental depression, and dragging legs, and human CD138(+)CD38(+) cells were detected in the bone marrow (BM) . Furthermore, bortezomib (BTZ) treatment given once the tumor was established significantly reduced the tumor burden[ (5.7±0.2) % vs (21.3±2.1) %, P<0.01]. Human CD138(+)CD38(+) cells were not detected in the BM of the MM.1S or NCI-H929 groups. Conclusion: The results of this study suggest that the mouse models constructed by the three cell lines (ARP1, MM.1S, and NCI-H929) can be used as models for the pathogenesis and clinical research of MM.


Subject(s)
Animals , Bortezomib/therapeutic use , Cell Line, Tumor , Disease Models, Animal , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Multiple Myeloma/drug therapy
10.
Article in Chinese | WPRIM | ID: wpr-928188

ABSTRACT

This study explored whether Sagittaria sagittifolia polysaccharides(SSP) activates the nuclear factor erythroid-2-related factor2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway to protect against liver damage jointly induced by multiple heavy metals. First, based on the proportion of dietary intake of six heavy metals in rice available in Beijing market, a heavy metal mixture was prepared for inducing mouse liver injury and HepG2 cell injury. Forty male Kunming mice were divided into five groups: control group, model group, glutathione positive control group, and low-and high-dose SSP groups, with eight mice in each group. After 30 days of intragastric administration, the liver injury in mice was observed by HE staining. In the in vitro experiment, MTT assay was conducted to detect the effects of SSP at 0.25, 0.5, 1, and 2 mg·mL~(-1) on HepG2 cell survival at different time points. The content of alanine transaminase(ALT) and aspartate aminotransferase(AST) in the 48-h cell culture fluid was measured using micro-plate cultivation method, followed by the detection of the change in reactive oxygen species(ROS) content by flow cytometry. The mRNA expression levels of Nrf2 and HO-1 in cells were determined by RT-PCR, and their protein expression by Western blot. HE staining results showed that compared with the model group, the SSP administration groups exhibited significantly alleviated inflammatory cell infiltration and fatty infiltration in the liver, with better outcomes observed in the high-dose SSP group. In the in vitro MTT assay, compared with the model group, SSP at four concentrations all significantly increased the cell survival rate, decreased the ALT, AST, and ROS content(P<0.05), and down-regulated Nrf2 and HO-1 mRNA and protein expression(P<0.05). SSP significantly improves inflammatory infiltration in the liver tissue of mice exposed to a variety of heavy metals and corrects the liver fat degeneration, which may be related to its regulation of the Nrf2/HO-1 signaling pathway, reduction of ROS, and alleviation of oxidative damage.


Subject(s)
Animals , Heme Oxygenase-1/metabolism , Liver , Male , Metals, Heavy/metabolism , Mice , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Polysaccharides/pharmacology , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , Sagittaria/metabolism
11.
Article in English | WPRIM | ID: wpr-925042

ABSTRACT

Objectives@#The aim of this study was to characterize the benefits of converting Electronic Medical Records (EMRs) to a common data model (CDM) and to assess the potential of CDM-converted data to rapidly generate insights for benefit-risk assessments in post-market regulatory evaluation and decisions. @*Methods@#EMRs from January 2013 to December 2016 were mapped onto the Observational Medical Outcomes Partnership-CDM (OMOP-CDM) schema. Vocabulary mappings were applied to convert source data values into OMOP-CDM-endorsed terminologies. Existing analytic codes used in a prior OMOP-CDM drug utilization study were modified to conduct an illustrative analysis of oral anticoagulants used for atrial fibrillation in Singapore and South Korea, resembling a typical benefit-risk assessment. A novel visualization is proposed to represent the comparative effectiveness, safety and utilization of the drugs. @*Results@#Over 90% of records were mapped onto the OMOP-CDM. The CDM data structures and analytic code templates simplified the querying of data for the analysis. In total, 2,419 patients from Singapore and South Korea fulfilled the study criteria, the majority of whom were warfarin users. After 3 months of follow-up, differences in cumulative incidence of bleeding and thromboembolic events were observable via the proposed visualization, surfacing insights as to the agent of preference in a given clinical setting, which may meaningfully inform regulatory decision-making. @*Conclusions@#While the structure of the OMOP-CDM and its accessory tools facilitate real-world data analysis, extending them to fulfil regulatory analytic purposes in the post-market setting, such as benefit-risk assessments, may require layering on additional analytic tools and visualization techniques.

12.
Article in Chinese | WPRIM | ID: wpr-936308

ABSTRACT

OBJECTIVE@#To evaluate the early and mid-term clinical results of medial parapatellar soft tissue overlapping suture in total knee arthroplasty for treatment of severe osteoarthritis combined with permanent patellar dislocation.@*METHODS@#We retrospectively analyzed the data of 12 patients (12 knees) diagnosed with severe knee osteoarthritis combined with permanent patellar dislocation undergoing total knee arthroplasty with medial parapatellar soft tissue overlapping suture. Knee Society Score (KSS), University of California Los Angeles (UCLA) activity-level rating, Visual Analog Scale (VAS) pain score, and knee range of motion of the patients were assessed before and 2 years after the surgery. Anteroposterior and lateral radiographs of the knee joint, full-length standing radiographs of the lower limbs and patellar axial radiographs were evaluated.@*RESULTS@#The mean Knee Society Score of the patients increased from 34.2±11.1 before surgery to 73.5±6.3 at two years after the surgery (P < 0.001). The UCLA activity-level rating increased from an average of 3.8 ± 0.8 before surgery to 5.8 ± 0.6 at two years postoperatively (P=0.003). The mean VAS pain score decreased from 42.8±6.0 before surgery to 20.1±3.7 (P < 0.001) and the range of motion of the knee joint increased from 74.6±8.9 degrees to 97.5±4.5 degrees at two years (P < 0.001). The radiographs showed no signs of subluxation or dislocation of the patella in all the patients.@*CONCLUSIONS@#Medial parapatellar soft tissue overlapping suture in total knee arthroplasty can achieve good early and mid-term clinical results for treatment of severe osteoarthritis combined with permanent patellar dislocation.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Humans , Osteoarthritis, Knee/surgery , Patella/surgery , Retrospective Studies , Sutures
13.
Article in English | WPRIM | ID: wpr-874629

ABSTRACT

Background and Objectives@#The immunomodulatory potential of mesenchymal stem cells (MSCs) can be regulated by a variety of molecules, especially cytokines. The inflammatory cytokine, TNF-like ligand 1A (TL1A), has been reported as an inflammation stimulator in-multiple autoimmune diseases. Here, we studied the effects of TL1A/TNF-receptor 2 (TNFR2) pathway on the therapeutic potency of bone marrow-derived MSCs (BMSCs). @*Methods@#and Results: BMSCs, fibroblast-like synoviocytes (FLSs), and H9 and jurkat human T lymphocytes were used in this study. BMSCs paracrine activities, differentiation, proliferation, and migration were investigated after stimulation with TL1A, and intervened with anti-TNFR2. Additionally, the effects of TL1A on BMSCs therapeutic potency were evaluated by treating RA-FLSs, and H9 and jurkat T cells with TL1A-stimulated BMSCs conditioned medium (CM). Indian hedgehog (IHH) involvement was determined by gene silencing and treatment by recombinant IHH (rIHH). TL1A induced BMSCs stemness-related genes, COX-2, IL-6, IDO, TGF-β and HGF through TNFR2. Also, TL1A corrected biased differentiation and increased proliferation, and migration through TNFR2. Meanwhile, CM of TL1A-stimulated BMSCs decreased the inflammatory markers of RA-FLSs and T cells. Moreover, TL1A-stimulated BMSCs experienced IHH up-regulation coupled with NF-κB and STAT3 signaling up-regulation, while p53 and oxidative stress were down-regulated. Furthermore, treatment of BMSCs by rIHH increased their anti-inflammatory effects.More importantly, knockdown of IHH decreased the ability of TL1A-stimulated BMSCs to alleviating the inflammation in RA-FLSs and T cells. @*Conclusions@#This study reports the effects of TL1A/TNFR2 pathway on the biological behaviors and therapeutic potency of BMSCs through IHH. These findings could introduce novel procedures to increase the stemness of MSCs in cellular therapy.

14.
Article in Chinese | WPRIM | ID: wpr-908108

ABSTRACT

Objective:To summarize the practical and nursing experience of early activity program for patients after cardiac valve replacement.Methods:Totally 156 patients after cardiac valve replacement from December 2018 to June 2019 were selected. Refer to the seven-steps of cardiac rehabilitation recommended by American Heart Association with daily activity training and Guidelines for cardiovascular rehabilitation and secondary prevention in China, an early activity program based on corrected modified early warning score (MEWS) was offered to the patients, than its effect was evaluated.Results:All the 156 patients were successfully extubated, no adverse events such as pressure ulcers, pipe slip-off and wound dehiscence occurred.Conclusion:On the basis of the correct evaluation of the patient's condition after heart valve replacement, early activities can promote the recovery of cardiopulmonary function and accelerate the recovery of the patient.

15.
Article in Chinese | WPRIM | ID: wpr-906470

ABSTRACT

Objective:To systematically sort out and summarize the medication rules of clinical prescriptions for coronary heart disease with heart failure of Qi deficiency and blood stasis syndrome,and to provide reference for selecting prescriptions and medications for the treatment of coronary heart disease (CHD) with traditional Chinese medicine (TCM). Method:All relevant literature concerning the treatment of CHD with compound TCM prescriptions for Qi deficiency and blood statis syndrome from 2000 to 2020 were retrieved from the China National Knowledge Network (CNKI),WanFang database (WanFang),and VIP journal database (VIP),and the names of prescriptions and drug components were extracted,followed by the frequency of drug use and drug category. Association rules of high-frequency drugs were analyzed by SPSS 18.0,and systematic clustering analysis was conducted by SPSS 21.0. Result:Finally,41 qualified literature articles covering 35 prescriptons and 66 drugs were included in the study. The total frequency of the drugs was 433 times. Among them,there were a total of 25 traditional Chinese medicines with a frequency of ≥5 times. The top 3 frequently used Chinese medicines were Astragali Radix (8.8%),Salviae Miltiorrhizae Radix et Rhizoma (7.2%),Chuanxiong Rhizoma (5.8%). A total of 15 types of drugs were involved,among which tonic drugs (31.4%),blood promoting and blood stasis drugs (28.2%),and hydration and dampening drugs (7.6%) were used most frequently. The association rule analysis of traditional Chinese medicines with frequency of ≥ 5 showed that there were 13 pairs of binomial associations in 25 traditional Chinese medicines,with Astragali Radix in combination with Salviae Miltiorrhizae Radix et Rhizoma,Chuanxiong Rhizoma,Carthami Flos,et al. There were 8 groups of three associations,with Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,and Chuanxiong Rhizoma as the main combinations. A systematic clustering analysis showed that the clustering effect was best when the 25 traditional Chinese medicines were clustered into 5 categories. Conclusion:The treatment of coronary heart disease with heart failure of Qi deficiency and blood stasis syndrome is based on replenishing qi and activating blood circulation,supplemented by warming yang,diuresis,and phlegm-resolving drugs,which can enhance the clinical efficacy. Two basic prescriptions of Buyang Huanwutang and Si junzitang are extracted. Other combinations of prescriptions and drugs can provide references for the clinical treatment of coronary heart disease with heart failure.

16.
Article in Chinese | WPRIM | ID: wpr-906334

ABSTRACT

Objective:To observe the effect of modified Cangfu Daotantang on metabolism and pregnancy in patients with spleen deficiency and phlegm-dampness type polycystic ovary syndrome (PCOS). Method:One hundred and twelve patients were randomly divided into control group and observation group according to the random number table. Both groups took non-pharmacological interventions, oral metformin hydrochloride, 500mg/time, 3 times/day; oral ethinyl estradiol and cyproterone tablets, 1 tablet/time, 1 time/day, starting from the third to fifth day of menstruation and lasting for twenty-one days, for a total of 3 menstrual cycles. Patients in control group additionally took Erchen pills orally, 10 g/time, 2 times/day, while patients in observation group additionally took modified Cangfu Daotantang orally, 1 dose/day. The course of treatment was six menstrual cycles in both groups (or termination after conception). The waist-to-hip ratio (WHR), body mass index (BMI), insulin resistance index (HOMA-IR), pancreatic <italic>β</italic>-cell function (HOMA-<italic>β</italic>), triglycerides (TG), low-density lipoprotein (LDL) and non-high-density lipoprotein (nHDL) elevation after treatment were compared. The number of ovulation cycles monitored by B-ultrasound (6 menstrual cycles), ovulation rate, human chorionic gonadotropin (HCG) day endometrial thickness, follicle diameter, cervical mucus score>8 points and endometrial morphology type A rate were measured and recorded. The recovery of menstruation, pregnancy and early miscarriage were recorded. Luteinizing hormone (LH), estradiol (E<sub>2</sub>), follicle stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS), testosterone (T), anti-Müllerian hormone (AMH) levels, and insulin before and after treatment -Like growth factor-1 (IGF-1), leptin (LP), adiponectin (APN), growth differentiation factor-9 (GDF-9) and tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>) levels were detected. Result:WHR, BMI and HOMA-IR levels of the observation group were lower than those of the control group (<italic>P</italic><0.05, <italic>P</italic><0.01). HOMA-<italic>β</italic> level was higher than that in the control group (<italic>P</italic><0.01). The increase rates of LDL, TG, and nHDL in the observation group were 19.61%(10/51),25.49%(13/51),23.53%(12/51), respectively, lower than 41.18%(21/51),47.06%(24/51),45.10%(23/51)respectively in the control group (<italic>χ</italic><sup>2</sup>=5.607, <italic>χ</italic><sup>2</sup>=5.131, <italic>χ</italic><sup>2</sup>=5.263, <italic>P</italic><0.05). The menstrual recovery rate in the observation group was 90.20% (46/51), higher than 72.55% (37/51) in the control group (<italic>χ</italic><sup>2</sup>=5.239,<italic>P</italic><0.05). The observation group had more ovulation cycles than the control group (<italic>P</italic><0.01). The pregnancy rate in the observation group was 50.98% (26/51), higher than 31.37% (16/51) in the control group (<italic>χ</italic><sup>2</sup>=4.047,<italic>P</italic><0.05). On HCG day after treatment, the endometrial thickness and follicle diameter in the observation group were better than those in the control group (<italic>P</italic><0.01). The proportion of patients with cervical mucus score> 8 points was 78.43% (40/51) in the observation group, higher than 56.86% (29/51) in the control group (<italic>χ</italic><sup>2</sup>=5.420,<italic>P</italic><0.05). The intimal morphology type A rate in the observation group was 52.94% (27/51), higher than 31.37% (16/51) in the control group (<italic>χ</italic><sup>2</sup>=4.864,<italic>P</italic><0.05). The levels of AMH, E<sub>2</sub>, DHEAS, LH, T , IGF-1, LP and TNF-<italic>α</italic> in the observation group were lower than those in the control group (<italic>P</italic><0.01), while the APN and GDF-9 levels were superior to those in the control group (<italic>P</italic><0.01). Conclusion:On the basis of conventional western medicine intervention, modified Cangfu Daotantang can regulate abnormal metabolism and reproductive endocrine in patients with PCOS, improve conception, and regulate the expression of IGF-1, GDF-9, adipocytokines and inflammatory factors, improve ovulation and improve pregnancy rate.

17.
Article in Chinese | WPRIM | ID: wpr-906111

ABSTRACT

Objective:To investigate the effect of total ginsenoside ginseng root on the learning and memory impairment and anxiety of hindlimb suspension rats by detecting the performance of rats in the water maze, elevated plus maze, and the expression of hypothalamic-pituitary-adrenal (HPA) axis, inflammatory factors and tryptophan pathway related factors through the intervention of ginsenosides in hindlimb suspension rats. Method:The Wistar male rats were divided into normal group, hindlimb suspension model group, Huperzine A group (0.1 mg·kg<sup>-1</sup>), and total ginsenoside ginseng root low and high dose groups (100, 200 mg·kg<sup>-1</sup>), with 8 rats in each group. Except for the normal group, the rats in the other groups maintained a -30° hindlimb suspension state for 24 h. The normal group and the model group received intragastric administration of 10 mL·kg<sup>-1</sup> pure water . After 28 days of continuous administration, the water maze and elevated plus maze behavioral tests were performed. After the tests, blood was taken from the abdominal aorta, and the rat brain cortex was peeled off on ice, quenched with liquid nitrogen, and stored at -80 ℃ for later use. LC-MS/MS was used to detect neurotransmitter levels of dopamine, acetylcholine, glutamate, <italic>γ</italic>-aminobutyric acid and tryptophan pathway metabolites (tryptophan, 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, kynurenine, 3-hydroxykynurenine, and kynurenine) in rat brain cortex. An enzyme-linked immunosorbent assay (ELISA) kit was used to detect the levels of inflammatory factors interleukin-6 (IL-6), interleukin-10 (IL-10, the HPA axis-related hormone corticotropin (ACTH), and the level of corticosterone (CORT). Result:Compared with the normal group, the escape latency in the water maze significantly increased, the number of crossings was significantly reduced, and the number of open-arm entry and the percentage of open-arm entry were significantly reduced in the elevated plus maze in model group (<italic>P</italic><0.05,<italic> P</italic><0.01), the content of dopamine, acetylcholine, glutamic acid, and <italic>γ</italic>-aminobutyric acid in the cortex decreased, kynurenine and kynurenic acid showed an upward trend, 3-hydroxykynurenine, 5-hydroxytryptamine, 5-hydroxyindole acetic acid showed a downward trend, and the levels of IL-6, IL-10, ACTH, and CORT in the serum significantly increased (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the model group of rats, total ginsenoside ginseng root low and high dose groups group reduced the avoidance latency in the water maze, and increased the number of crossings and the number of open arms of the elevated plus maze, dopamine, acetylcholine, glutamate, and <italic>γ</italic>-aminobutyl content increased, while kynurenine and kynurenic acid showed a downward trend, 3-hydroxykynurenine, serotonin, and 5-hydroxyindole acetic acid showed an upward trend, and IL-6, IL-10, ACTH, and CORT factor levels were down-regulated(<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:Hindlimb suspension for 28 days in simulated microgravity can impair the learning and memory ability of rats and cause anxiety-like behaviors. Total ginsenoside ginseng root can improve their learning and memory impairment and anxiety-like behaviors. The mechanism may be mainly related to inhibiting body inflammation and regulating HPA axis imbalance.

18.
Article in Chinese | WPRIM | ID: wpr-906109

ABSTRACT

Objective:To explore the possible mechanism of Yanghe Huayantang in reversing the drug resistance of breast cancer by observing the effect of Yanghe Huayantang on the transplant tumor of tamoxifen (TAM)-resistant breast cancer and its influences on the interaction pathway of estrogen receptor (ER)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian rapamycin target protein (mTOR). Method:Fifty mice were randomly divided into 5 groups: blank group, model group, Yanghe Huayantang group, everolimus group, and Yanghe Huayantang+everolimus group. The model of kidney deficiency was established by bilateral ovariectomy, and the blank group was treated with sham operation. Three days after the establishment of the model, all the five groups of mice were inoculated with breast cancer TAM drug-resistant cells (MCF-7/TAM<sup>-</sup>) to establish breast cancer TAM -resistant transplanted tumor model. After successful modeling, Yanghe Huayantang group received intragastric administration of Yanghe Huayantang (traditional Chinese medicine preparation 20 mL·kg<sup>-1</sup>), everolimus group received intraperitoneal injection of everolimus (10 mg·kg<sup>-1</sup>). Yanghe Huayantang + everolimus group received Yanghe Huayantang by intragastric administration and everolimus by intraperitoneal injection. The blank group and model group received intragastric administration and intraperitoneal injection of phosphate buffer (PBS). Drug administration was lasted for 28 days in all groups, once a day. After administration, the tumor tissue was separated and weighed, and the tumor inhibition rate was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of tumor tissue. Immunofluorescence and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect the expression of PI3K, Akt, mTOR, ER protein and mRNA in tumor tissue. Result:Compared with the model group, the tumor volume and tumor weight of Yanghe Huayantang group decreased significantly on the 12th, 20th and 28th days (<italic>P</italic><0.01), and the tumor inhibition rate increased significantly (<italic>P</italic><0.01).Yanghe Huayantang group significantly reduced the density of tumor cells and caused tumor cell necrosis. Compared with the model group, Yanghe Huayantang group, everolimus group and Yanghe Huayantang+everolimus group inhibited the expression of PI3K, Akt, mTOR protein and mRNA (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the blank group, Yanghe Huayantang group, everolimus group and Yanghe Huayantang+everolimus group all inhibited the protein and mRNA expression of ER, and mRNA expression of ER in Yanghe Huayantang+everolimus group was significantly lower than that in the model group (<italic>P</italic><0.01). Conclusion:Yanghe Huayantang can inhibit the growth of TAM-resistant breast cancer. The mechanism may be that Yanghe Huayantang can reverse the TAM resistance of breast cancer by down-regulating the expression of key molecules of ER/PI3K/Akt/mTOR cross-signal pathway.

19.
Article in Chinese | WPRIM | ID: wpr-906055

ABSTRACT

Objective:To explore the correlations of the severity of heart failure related to coronary heart disease arising from Qi deficiency and blood stasis with cardiac function indexes, energy metabolism indexes, coagulation function indexes, and inflammatory factors, in order to provide a scientific basis for further research on the biological foundation of this disease. Method:Two hundred patients with heart failure related to coronary heart disease of Qi deficiency and blood stasis syndrome were collected and then classified into mild, moderate and severe groups according to their scores of Qi deficiency and blood stasis syndrome. Meanwhile, 40 healthy persons confirmed by physical examination during the same period were included into the control group. Such biological indexes as cardiac function indexes, energy metabolism indexes, coagulation function indexes, and inflammatory factors were determined in patients of each group for comparison. Then the Spearman rank correlation analysis was conducted to figure out the correlations between differential indexes and the severity of Qi deficiency and blood stasis syndrome, followed by the determination of risk factors for the severity of Qi deficiency and blood stasis syndrome by ordered logistic regression analysis. Result:The cardiac function indexes, energy metabolism indexes, coagulation function indexes, and inflammatory factors in patients with heart failure related to coronary heart disease arising from Qi deficiency and blood stasis varied significantly. There were significant statistical differences in the levels of N-terminal pro-B-type natriuretic peptide (NT-ProBNP), 6-minute walk test (6MWT), heart-type fatty acid-binging protein (H-FABP), prothrombin time (PT), activated partial thromboplastin time (APTT), tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>), and nitric oxide (NO) among the mild, moderate, and severe groups (<italic>P</italic><0.05). The severity of Qi deficiency and blood stasis syndrome was positively correlated with NT-ProBNP (<italic>r</italic>=0.144), PT (<italic>r</italic>=0.173), and APTT (<italic>r</italic>=0.144), but negatively with 6MWT (<italic>r</italic>=-0.287). The 6MWT[odds ratio(OR)=0.995, 95% confidence interval(CI) 0.991-0.998),<italic>P</italic><0.01] and APTT(OR=1.088,95%CI 1.021-1.157,<italic>P</italic><0.01) were independent risk factors affecting the severity of heart failure related to coronary heart disease arising from Qi deficiency and blood stasis. Conclusion:The severity of heart failure related to coronary heart disease of Qi deficiency and blood stasis syndrome is closely related to NT-ProBNP, 6MWT, H-FABP, PT, APTT, TNF-<italic>α</italic>, and NO. Moreover, 6MWT and APTT can be used as independent risk factors to evaluate the severity of patients with heart failure related to coronary heart disease due to Qi deficiency and blood stasis.

20.
Article in Chinese | WPRIM | ID: wpr-905974

ABSTRACT

Objective:To explore the mechanism of Xiaojinwan in treating breast cancer bone metastases through cell experiments and bioinformatic analysis. Method:The inhibitory effect of Xiaojinwan on MCF-7 cell viability was detected by cell counting kit-8 (CCK-8) assay. The key components and targets responsible for Xiaojinwan in inhibiting breast cancer bone metastases were predicted by network pharmacology and molecular docking. The active components and targets of Xiaojinwan were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCSMP) and SwissTarget Prediction, and the breast cancer bone metastases-related targets from GeneCards and DisGeNET. The results were imported into STRING for constructing a protein-protein interaction (PPI) network, followed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using DAVID. A network of the active components of Xiaojinwan-breast cancer bone metastases-related targets-pathways was constructed using Cytoscape 3.7.2. AutoDock 4 was employed for molecular docking. The protein expression levels of matrix metallopmteinase-9 (MMP-9), hypoxia-inducible factor 1<italic>α </italic>(HIF1A), and androgen receptor (AR) were assayed by Western blot. Result:Xiaojinwan inhibited the viability of MCF-7 cells and acted on breast cancer bone metastases through such processes as redox and protein autophosphorylation. KEGG enrichment analysis showed that HIF-1, vascular endothelial growth factor (VEGF) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathways were involved. As verified by molecular docking, the active components such as eucalyptin stably bound to AR and MMP-9. Western blot indicated that Xiaojinwan dose-dependently inhibited the expression of MMP-9 and HIF1A proteins in MCF-7 cells. Conclusion:Xiaojinwan acts on AR and MMP-9 through HIF, VEGF and other related signaling pathways, thereby improving hypoxia in tumor microenvironment, inhibiting angiogenesis, and reducing cell invasion and viability.

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