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OBJECTIVE To explore standardized evaluation process for clinical comprehensive evaluation of blood lipid- regulating drugs and perform rapid assessment of clinical comprehensive evaluation of blood lipid-regulating drugs with different mechanisms so as to provide reference for the drug catalogue selection and rational drug use of medical institutions. METHODS Referring to guidelines and consensus such as the guideline for the management of comprehensive clinical evaluation of drugs， the methods such as literature research， expert interviews， and Delphi expert consultation were used to establish a multi-dimensional and multi-criteria clinical comprehensive evaluation index system and quantitative scoring table for blood lipid-regulating drugs around the two main lines of technical evaluation and policy evaluation. Then 13 blood lipid-regulating drugs with different mechanisms in 21 third-grade class-A medical institutions from five provinces and regions of Northwest China were scored from both technical and policy dimensions to form a comprehensive evaluation result. RESULTS The clinical comprehensive evaluation index system and corresponding rapid evaluation quantitative scoring table were constructed for blood lipid-regulating drugs in the five northwest provinces and regions. The technicalevaluation section included 6 primary indicators， 13 secondary indicators， and 34 tertiary indicators， totaling 110 points. The policy evaluation section included 4 primary indicators and 6 secondary indicators， with a total score of 40 points （30 points for some drugs） and a total score of 150 points （or 140 points）. The scoring results showed that the highest score was atorvastatin， followed by rosuvastatin and simvastatin. CONCLUSIONS Statins are still the cornerstone of drug therapy for patients with dyslipidemia； the rapid evaluation quantitative scoring table constructed in this study is comprehensive， systematic and operable. The evaluation process in this study can provide empirical references for other groups to exploring the standardized path and quality control mechanism of clinical comprehensive evaluation of drugs.
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Objective:To investigate the effect of the combination of Auto-prescription and ODM full on image quality and radiation dose of chest enhanced CT inorder to explore the feasibility of individualized low radiation dose chest enhanced CT. Methods:The phantoms PH-75 in two sizes were scanned with four scanning modes: group A, 120 kVp + Smart-mA; group B, 120 kVp + Smart-mA+ ODM full; group C, Auto-prescription + Smart-mA; group D, Auto-prescription + Smart-mA+ ODM full. The images of each group were reconstructed with 40%-80% ASIR-V (interval 20%), recorded as A 1-3-D 1-3. Image quality and radiation dose were evaluated in order to obtain optimal scanning modes. Totally 35 cases(from the First Hospital of Dalian Medical University during November 2021 to July 2022) of chest enhancement CT were collected prospectively in the clinical study using the parameters of D 2 group recorded as D patients. Patients in this group received chest enhancement CT scanning for the second time within three months. The CT parameters in first enhanced scanning recorded as A patient were as same as those in group A 1, and the parameters in second scanning recorded as D patient were as same as those in group D 2. The SNRs, CNRs, subjective grading and imaging findings of the lesion in two groups were compared. Results:In phantom study, the radiation dose of each group was statistically significant, and that in D group was the lowest. For two sizes of phantoms, A 1 was uesd as the control group in pairwise comparison. The SDs of B 1, C 1, and D 2 images had no statistical difference with that of A 1 ( P > 0.05), and SD of D 1was higher than that of A 1, and SDs of other groups were lower than that of A 1( F=10.77, 122.50, P<0.05). CNR of B 1 had no statistical difference with that of A 1, and the CNRs of other groups were higher( F=136.20, 30.21, P<0.05). Subjective scores of A 2, C 2, D 2 had no statistical difference with that of A 1 and those of other groups were lower than that of A 1( H=52.89, 43.95, P<0.05). In clinical study, 80 kVp was uesd for 22 cases and 100 kVp was used for 13 cases in D patients group. SNRs and CNRs in the D patients group were all higher than those in the A patients group ( P > 0.05). The consistency of image quality scores for two observers was good ( kappa = 0.754, P < 0.05). The median scores of the two groups were (4, 4). Conclusion:Auto-prescription combined with ODM full in chest enhanced CT imaging can achieve individualized low radiation dose with meeting the requirements of image quality and clinical diagnosis.
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Objective:To evaluate the rehabilitation efficacy of early mobilization based on collaboration care model for patients with laparoscopic colorectal surgery.Methods:Cluster sampling method was used in the department to recruit colorectal cancer patients with laparoscopic surgery. The control group (49 cases) received routine perioperative care and exercise, and the intervention group (47 cases) received the coordinated early mobilization combined with routine perioperative care and exercise, from January to March 2019. Primary outcome were health status and the proportion of patients returning to preoperative functional walking capacity (6-min walk test) at 4 weeks after surgery. The in-hospital mobilization (time out-of-bed), time to achieve discharge criteria, time to recover gastrointestinal function and complication rate were explored.Results:In intervention group,89.4%(42/47) of patients achieved mobilization target on 4 days after surgery compared with 42.6%(20/47) on the day of surgery. Time out of bed were greater in the intervention group compared with the control group, and there were differences between the two groups( Z values were -8.437--7.381, P<0.01). Time to recover gastrointestinal function and the recovery of energy on 3 days after surgery were (58.74±17.41) h, (59.02±9.46) points in the observation group, and (71.82±21.53) h, (62.61±7.68) points in the control group, and there were significant differences between the two groups ( t values were -3.263, -2.046, P<0.05). But other outcome measures were not different between the two groups ( P>0.05). Conclusions:For colorectal laparoscopic surgery patients, the coordinated early mobilization improved the adherence to ambulation, in-hospital mobilization, time to recover gastrointestinal function and recovery of energy to promote rehabilitation.
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Calnexin is a lectin-like molecular chaperone protein on the endoplasmic reticulum, mediating unfolded protein responses, the endoplasmic reticulum Ca homeostasis, and Ca signals conduction. In recent years, studies have found that calnexin plays a key role in the heart diseases. This study aims to explore the role of calnexin in the activation of cardiac fibroblasts. A transverse aortic constriction (TAC) mouse model was established to observe the activation of cardiac fibroblasts , and the cardiac fibroblasts activation model was established by transforming growth factor β1 (TGFβ1) stimulation. The adenovirus was respectively used to gene overexpression and silencing calnexin in cardiac fibroblasts to elucidate the relationship between calnexin and cardiac fibroblasts activation, as well as the possible underlying mechanism. We confirmed the establishment of TAC model by echocardiography, hematoxylin-eosin, Masson, and Sirius red staining, and detecting the expression of cardiac fibrosis markers in cardiac tissues. After TGFβ1 stimulation, markers of the activation of cardiac fibroblast, and proliferation and migration of cardiac fibroblast were detected by quantitative PCR, Western blot, EdU assay, and wound healing assay respectively. The results showed that the calnexin expression was reduced in both the TAC mice model and the activated cardiac fibroblasts. The overexpression of calnexin relieved cardiac fibroblasts activation, in contrast, the silencing of calnexin promoted cardiac fibroblasts activation. Furthermore, we found that the endoplasmic reticulum stress was activated during cardiac fibroblasts activation, and endoplasmic reticulum stress was relieved after overexpression of calnexin. Conversely, after the silencing of calnexin, endoplasmic reticulum stress was further aggravated, accompanying with the activation of cardiac fibroblasts. Our data suggest that the overexpression of calnexin may prevent cardiac fibroblasts against activation by alleviating endoplasmic reticulum stress.
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The efficacy and safety of co-transplantation of unrelated donor peripheral blood stem cells (UD-PBSCs) combined with umbilical cord mesenchymal stem cells (UC-MSCs) in refractory severe aplastic anemia-Ⅱ(RSAA-Ⅱ) were analyzed retrospectively. Fifteen patients with RSAA-Ⅱ underwent UD-PBSCs and UC-MSCs co-transplantation, among whom 14 cases had hematopoietic reconstitution without severe graft versus-host disease (GVHD). The 5-year overall survival rate was 78.57%. Combination of UD-PBSCs and UC-MSCs transplantation could be a safe and effective option for RSAA-Ⅱ.
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Objective@#To evaluate the efficacy and safety of mesenchymal stem cells in allogeneic hematopoietic stem cell transplantation for patients with refractory severe aplastic anemia (R-SAA) .@*Method@#The clinical data of 25 R-SAA patients receiving co-transplantation of mesenchymal stem cells combined with peripheral blood stem cells from sibling donors (10 cases) and unrelated donors (15 cases) from March 2010 to July 2018 in Zhengzhou University Affiliated Tumor Hospital were retrospectively analyzed. Antithymocyte globulin (ATG) treatment was ineffective/relapsed in 11 cases, and cyclosporine (CsA) treatment ineffective/relapsed in 14 cases.@*Results@#There were 13 male and 12 female among these patients. One patient had a primary graft failure, one patient had a poorly engraftment of platelets, and the remaining 23 patients achieved hematopoietic engraftment. The median time of granulocyte engraftment was 12.5 (10-23) days and 15 (11-25) days for megakaryocyte. Incidences of grade Ⅰ/Ⅱ acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) were 37.5% (9/24) and 21.7% (5/23) , respectively. There was no severe GVHD and no severe complications that related to transplantation. 21 of 25 (84%) patients were alive with a median follow-up of 22.9 (1.6-107.8) months. The 5-year overall survival rate after transplantation was (83.6±7.5) %.@*Conclusion@#The combination of mesenchymal stem cells is reliable and safe in the treatment of R-SAA in peripheral blood stem cell transplantation of unrelated donors and sibling donors, which could significantly reduce the incidence of GVHD and severe transplantation-related complications.
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The aim of this study was to observe whether necroptosis is involved in the process of cardiac hypertrophy induced by pressure overload. SD rats underwent transverse abdominal aortic constriction (TAC) operation for establishing cardiac hypertrophy model. The structure and function of the left ventricle of rats were evaluated via echocardiography, left ventricular mass index, the expression of markers of cardiac hypertrophy and histological detection. Real-time PCR and Western blot were used to measure the gene and protein expression of receptor interacting protein kinase 1 and 3 (RIPK1 and RIPK3, the necroptosis markers) respectively. Four weeks after TAC operation, rat model for cardiac hypertrophy was established. The experimental data showed that the gene and protein expressions of RIPK1 and RIPK3 in the rat heart hypertrophic tissues after TAC for 4 weeks were increased significantly compared with those in the sham group. HE staining showed cardiomyocytes injury and hypertrophy in the hearts of TAC rat models. By transmission electron microscope, we observed that mitochondria of cardiomyocytes were damaged seriously in the TAC models. Treatment with losartan used, the selective antagonist of angiotensin II type I receptor could improve the cardiac function of TAC rats. Moreover, losartan treatment decreased the expression of RIPK1 and RIPK3 in heart tissues of TAC rats. The results suggest that necroptosis occurrs in the process of cardiac hypertrophy with pressure overload, and losartan could alleviate the cardiac hypertrophy and inhibit necroptosis.
Subject(s)
Animals , Rats , Apoptosis , Cardiomegaly , Pathology , Disease Models, Animal , Echocardiography , Heart , Losartan , Pharmacology , Myocytes, Cardiac , Pressure , Protein Serine-Threonine Kinases , Metabolism , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Receptor-Interacting Protein Serine-Threonine Kinases , MetabolismABSTRACT
The aim of this study is to construct specific shRNA expressing plasmids, and to observe their effects on H9c2 cardiomyocytes injury induced by hypoxia/reoxygenation (H/R). RIPK1 and RIPK3 are the key kinases mediating the process of necroptosis. Using recombinant DNA technology, we inserted the synthetic shRNA into pSUPER vector to construct RIPK1-shRNA or RIPK3-shRNA plasmid respectively. We transfected H9c2 cardiomyocytes with the two shRNA plasmids respectively, before we treated them with H/R stimulation. Then, we measured the relevant genes and proteins by real-time PCR and Western blot. Meanwhile,we detected the markers of necroptosis and cardiomyocytes injury. The results showed that inhibition of ripk1 or ripk3 gene expression by its specific shRNA might protect the cardiomyocytes injury induced by H/R stimulation.
Subject(s)
Animals , Rats , Apoptosis , Cell Hypoxia , Cell Line , Gene Expression , Myocytes, Cardiac , Pathology , Protein Serine-Threonine Kinases , Genetics , Metabolism , RNA, Small Interfering , Real-Time Polymerase Chain Reaction , Receptor-Interacting Protein Serine-Threonine Kinases , Genetics , Metabolism , TransfectionABSTRACT
Objective To estimate direct economic burden of patients with moderate to severe psoriasis in China,and to assess its influencing factors.Methods A questionnaire survey was carried out in 150 patients with moderate to severe psoriasis from 29 third-grade class-A hospitals in 7 cities.Data on demographic characteristics,clinical features and direct economic burden were collected.Descriptive statistics were performed to analyze the direct economic burden of moderate to severe psoriasis,and multiple regression analysis was carried out to determine predictors of cost of illness.Results The patients were aged (43.87 ± 13.42) years,with an average clinical course of 3 years(range,2-6 years).Of them,82 had moderate psoriasis,and 68 had severe psoriasis.The average direct cost was (6 452 ± 6 391)RMB per patient-year,with significant difference between the patients with moderate psoriasis and those with severe psoriasis ((4 163 ± 4 605) vs.(9 212 ± 7 146) RMB,z =5.70,P ＜ 0.001).Regression analysis indicated that disease severity,clinical type,hospitalization,complications,and inhabited cities were factors influencing the direct economic burden of patients with moderate to severe psoriasis.Conclusions The direct eonomic burden of severe psoriasis seems to be twice that of moderate psoriasis in China.Physicians should strengthen the control of complications and disease severity,and pay more attention to other types of psoriasis than psoriasis vulgaris,during the treatment of psoriasis.
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Objective:To get the basic situation of the list of low-price medicines and their sales in Tianjin to pro-vide future policy reference. Methods:The low-price medicine list was analyzed through different principles of classifica-tion including the National Essential medicine List ( NEML) , National Reimbursement medicine List ( NRML) and exclu-sive production. The study analyzed the sales status of the low-price medicines in the Tianjin from 2008 to 2011 using the Tianjin Urban Employee Basic Medical Insurance (UEBMI) database. Results:19 classes of chemical medicines and eight classes of traditional Chinese Medicine are included in the low-price medicine list. All of the medicines in the low-price list come from the NRML, and the replication ratio between the NEML and the low-price medicine list is 54. 1%. There are 41 exclusive productions and 149 exclusive formulation productions. From 2008 to 2011, the average ratio of the chemi-cal low-price medicines and traditional Chinese Medicine sales to total medicines sales are 4. 7% and 11. 0%, respective-ly. Both national essential medicines and exclusive formulation production sales ratios are increasing, however the sales ra-tio of exclusive production decreased from 2008 to 2011. Conclusion:The government should pay greater attention to the supply and production of the list’s exclusive production. The sales ratio of low-price medicines to total medicines sales is much lower in the retail pharmacies and tertiary medical institutions than other medical institutions. Suggestions:The gov-ernment should practice the shortage report system of common low-price medicine as soon as possible, with efforts made to implement the global budgeting policy and encourage sales enthusiasm for low-price medicines in retail pharmacies.
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This study is to investigate the effect of Euphorbia humifusa effective fraction (EHEF) on the CYP51 enzyme activity, the lanosterol content and the MEP, SUB gene expression of Trichophyton rubrum. Trichophyton rubrum was treated by EHEF for 7 days at 26 degrees C. The activity of CYP51 enzyme of Trichophyton rubrum in the cell membrane was determined by using ELISA kit, and the lanosterol content was investigated by using high performance liquid chromatography (HPLC), and the MEP, SUB gene expression of Trichophyton rubrum was detected with the reverse transcription polymerase chain reaction (RT-PCR) method. Results showed that EHEF can decrease the membrane CYP51 enzyme activity, and it also can accumulate the fungal lanosterol in a dose-dependent manner, and it also can decrease the gene expression of MEP and SUB. The antifungal mechanism of EHEF may be related to the inhibition on CYP51 enzyme activity, and to the effects on fungal cell membrane ergosterol biosynthesis. It may also play an antifungal effect by inhibiting the MEP, SUB gene expression of fungal proteases.