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This study was designed to evaluate the protective effect of CPD1, a novel phosphodiesterase 5 inhibitor, on renal interstitial fibrosis after unilateral renal ischemia-reperfusion injury (UIRI). Male BALB/c mice were subjected to UIRI, and treated with CPD1 once daily (i.g, 5 mg/kg). Contralateral nephrectomy was performed on day 10 after UIRI, and the UIRI kidneys were harvested on day 11. Hematoxylin-eosin (HE), Masson trichrome and Sirius Red staining methods were used to observe the renal tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of proteins related to fibrosis. HE, Sirius Red and Masson trichrome staining showed that CPD1-treated UIRI mice had lower extent of tubular epithelial cell injury and deposition of extracellular matrix (ECM) in renal interstitium compared with those in the fibrotic mouse kidneys. The results from immunohistochemistry and Western blot assay indicated significantly decreased protein expressions of type I collagen, fibronectin, plasminogen activator inhibitor-1 (PAI-1) and α-smooth muscle actin (α-SMA) after CPD1 treatment. In addition, CPD1 dose-dependently inhibited the expression of ECM-related proteins induced by transforming growth factor β1 (TGF-β1) in normal rat kidney interstitial fibroblasts (NRK-49F) and human renal tubular epithelial cell line (HK-2). In summary, the novel PDE inhibitor, CPD1, displays strong protective effects against UIRI and fibrosis by suppressing TGF-β signaling pathway and regulating the balance between ECM synthesis and degradation through PAI-1.
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Animals , Humans , Male , Mice , Rats , Extracellular Matrix Proteins , Fibrosis , Kidney , Kidney Diseases , Phosphodiesterase 5 Inhibitors , Plasminogen Activator Inhibitor 1ABSTRACT
Objective:To establish the norms of health-related physical fitness measurement scale (HRPFMS) for urban elderly in China, and provide reference for assessing the level of health-related physical fitness of the elderly.Methods:Conducting a large-scale epidemiological investigation with a multistage stratified sampling method among 5 833 urban elderly residents sampled from 6 regions in China.IBM SPSS 22.0 software was used for statistical analysis.The mean, percentile and threshold norms were established based on the characteristics of HRPFMS scores for urban elderly in China.Results:The mean, percentile and threshold norms of total, organic function, motor function and physical adaptive capacity of urban elderly in China were established according to gender and different age groups (60-64, 65-69, 70-74, 75-79, and ≥80 years old). The mean norm of the total scores of male in different age groups were 64.25±12.65, 60.55±12.48, 58.13±13.59, 56.66±12.44 and 53.50±14.66, respectively, and the mean norm of the total scores of women in different age groups were 59.77±12.12, 57.67±12.50, 54.30±12.25, 50.47±13.39 and 41.72±13.11, respectively. According to the mean± SD and mean±0.5 SD of the converted scores, the threshold norms of HRPFMS were divided into 5 states, namely very low, low, moderate, high and very high states, and the values were [0, 43.47], (43.47, 50.23], (50.23, 63.75], (63.75, 70.51] and (70.51, 100], respectively. Conclusion:The norms of HRPFMS for urban elderly in China are well-represented. It can provide evaluation criteria for Chinese elderly health-related physical fitness level.
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Objective:To develop health-related physical fitness measurement scale and assess its reliability and validity among older adults.Methods:The health-related physical fitness measurement scale was developed through Delphi method and field investigation method.And the authority coefficient, Kendall's coefficient and variation coefficient were analyzed.A multi-stage random sampling technique was adopted to select 410 older adults to investigate the reliability and validity of health-related physical fitness measurement scale with test-retest reliability, Cronbach's α coefficient and Guttman Split-Half coefficient and structural validity by IBM SPSS 20.0 and AMOS 22.0.Results:The health-related physical fitness measurement scale consisted of 3 dimensions (organic function, motor function, physical adaptive capacity) and 15 indexes.The Cronbach's α coefficient was 0.84.The Spearman-Brown correlation coefficient and Guttman Split-Half coefficient were both 0.82.The test-retest reliability between the first measurement and retest after 1 week was 0.84.Three factors were extracted by exploratory factor analysis, which were basically consistent with the theoretical concept of the scale, but the items of the theoretical conception were different from the actual ones.Confirmatory factor analysis based on the theoretical conception showed that all the indexes met the requirements of reference value as well(χ 2/ df=2.38, GFI=0.94, AGFI=0.91, CFI=0.92, TLI=0.91, TFI=0.92, RMSEA=0.06). Conclusion:The health-related physical fitness measurement scale has good reliability and validity in measuring the health fitness level of the elderly population in Guangzhou.
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OBJECTIVE@#To evaluate the reliability and validity of Healthy Fitness Measurement Scale V1.0 (HFMS V1.0) for assessing healthy fitness status of college students in Guangzhou.@*METHODS@#A total of 584 college students were evaluated with HFMS V1.0. The reliability and validity of HFMS V1.0 scale were assessed for its discrimination degree, Cronbach α coefficient, split-half reliability, test-retest reliability, content validity, structural validity, calibration validity and responsiveness.@*RESULTS@#The Cronbach α of HFMS V1.0 scale was 0.893, the split-half coefficient was 0.909, and the test-retest coefficient was 0.923. The correlation coefficients of each dimension with its subscales ranged from 0.687 to 0.931. The correlation coefficient between each item and its dimension ranged from 0.558 to 0.863(@*CONCLUSIONS@#HFMS V1.0 has high reliability and validity for evaluating healthy fitness status of college students.
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Humans , Factor Analysis, Statistical , Health Status , Psychometrics , Reproducibility of Results , Students , Surveys and QuestionnairesABSTRACT
Objective:To determine the optimal time to perform sentinel lymph node biopsy(SLNB)in patients with clinically node-negative disease and assess clinically node-positive patients who would acquire greater benefits from axillary downstaging surgery af-ter neoadjuvant chemotherapy(NAC).Methods:From October 2010 to November 2017,206 patients with breast cancer who under-went surgery after NAC were included in this retrospective study in Shandong Cancer Hospital Breast Cancer Center.Their clinicopatho-logic data were collected to discuss the correlation between axillary node pathologic complete response(apCR)and different molecu-lar subtypes.Results:Among 206 patients who received NAC,183 patients had clinically node-positive disease.The frequency of apCR after NAC was 33.3%(61/183),which was significantly higher in patients with human epidermal growth factor receptor 2(HER-2)-posi-tive subtype[with targeted therapy,62.1%(18/29);without targeted therapy,34.5%(10/29)]and triple-negative breast cancer(TNBC) (41.0%)(16/39)than in patients with HER-2-negative luminal subtype breast cancer[19.8%(17/86)](P<0.001). Among 23 patients with Cn0 tumors,the rate of positive sentinel lymph nodes after NAC was 26.1%(6/23);this rate was 36.4%(4/11),25.0%(1/4),and 12.5% (1/8)among patients with HER-2-negative luminal subtype breast cancer,TNBC,and HER-2-positive subtype breast cancer,respective-ly.Conclusions:Molecular subtypes could predict the chance of achieving apCR.For patients with clinically node-negative disease,it would be preferable to perform SLNB prior to NAC for patients with HER-2-negative luminal subtype breast cancer.SLNB after NAC for those with TNBC and HER-2-positive subtype breast cancer could decrease the chances of axillary lymph node dissection.For patients with initial clinically node-positive disease converting to clinically node-negative disease after NAC,especially in TNBC and HER-2-posi-tive subtype breast cancer,these patients might benefit more from axillary downstaging surgery after NAC.
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Objective:To undemtand the direction and synergic relationship of the reform policy of Hierarchical Medical Treatment from perspective of urban public hospital of Guangdong.Methods:Policy analysis and the rainbow model of integrated care.Results:58 pohcy documents were included in analysis.A policy package was established based on the rainbow model of integrated care.The direction of the reform policy was clear but the synergic relationship among some policy measures was still not precise.Conclusion:The policy package was on conceptual phase.It was necessary to supplement some reform policies and measures to build synergic relationship productively.
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Objective To reconstruct the original three-dimensional conformation of tumor resection tissue through the study of breast-conserving surgery excision specimens for part-mount sub-serial section and pathological three-dimensional (3D) reconstruction,to establish a new margin assessment model,and to guide tumor bed delineation individually for radiotherapy.Methods From February 2016 to February 2017,thirtythree eligible breast cancer patients underwent breast-conserving surgery in Breast Cancer Center of Shandong Cancer Hospital were recruited.The excision specimens were prepared with part-mount sub-serial section,and residual tumors were microscopically outlined,scanned and registered by Photoshop software.The 3D model of residual tumors was reconstructed with 3D-DOCTOR software to evaluate margin status and record pathological type,tumor length and 3D negative margin distance.The gross tumor volume (GTV) was delineated based on clips placed in the lumpectomy cavity.CTV1 and CTV2 were defined by adding uniform 1.00 cm and 1.50 cm margin based on GTV respectively.CTV3 and CTV4 were defined by adding 1.00 cm and 1.50 cm margin based on 3D boundary of excision tumor respectively,and compared the volume differences of CTV1 and CTV3,CTV2 and CTV4.Results Based on the marginal assessment results of 3D pathological reconstruction,the rates of false negatives during the intraoperative rapid pathological examination and postoperative routine pathological margin evaluation were 6.7％ (2/30) and 3.4％ (1/29) respectively.The pathological type of pathological large slice and routine pathological examination was consistent with rate of 93.9％ (31/33).The M(QR) tumor lengths of routine pathological and pathological 3D reconstruction were 1.90 (1.50-2.40) cm and 2.00 (1.60-2.70) cm respectively,with statistical difference between the two groups (Z =-2.438,P =0.015).The M(QR) volumes for CTV1,CTV2,CTV3,CTV4 were 70.76 (49.84-78.07)cm3,110.11 (83.38-126.17) cm3,23.85 (16.46-31.49)cm3 and 38.74 (30.47-50.58) cm3 respectively.There were statistical differences between CTV1 and CTV3,CTV2 and CTV4 (Z =-4.372,P ＜0.001;Z =-4.372,P ＜0.001).Conclusion The application of pathological 3D reconstruction technology can largely compensate for the shortcomings of the traditional margin assessment model,make the decisions of adjuvant treatment after breast-conserving surgery more accurate,and guide the tumor bed delineation individually for radiotherapy.
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Two types(A model and B model) of articular cartilage defect models were prepared by using adult New Zealand white rabbits. A model group was applied by drilling without through subchondral bone, whose right joint was repaired by composite scaffolds made by seed cell, gum-bletilla as well as Pluronic F-127, and left side was blank control. B model group was applied by subchondral drilling method, whose right joint was repaired by using composite scaffolds made by gum-bletilla and Pluronic F-127 without seed cells, and left side was blank control. Autogenous contrast was used in both model types. In addition, another group was applied with B model type rabbits, which was repaired with artificial complex material of Pluronic F-127 in both joint sides. 4, 12 and 24 weeks after operation, the animals were sacrificed and the samples were collected from repaired area for staining with HE, typeⅡcollagen immunohistochemical method, Alcian blue, and toluidine blue, and then were observed with optical microscope. Semi-quantitative scores were graded by referring to Wakitanis histological scoring standard to investigate the histomorphology of repaired tissue. Hyaline cartilage repairing was achieved in both Group A and Group B, with satisfactory results. There were no significant differences on repairing effects for articular cartilage defects between composite scaffolds made by seed cell, gum-bletilla and Pluronic F-127, and the composite scaffolds made by gum-bletilla and Pluronic F-127 without seed cell. Better repairing effects for articular cartilage defects were observed in groups with use of gum-bletilla, indicating that gum-bletilla is a vital part in composite scaffolds material.
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Animals , Rabbits , Arthroplasty, Subchondral , Cartilage, Articular , General Surgery , Cells, Cultured , Orchidaceae , Chemistry , Plant Gums , Chemistry , Poloxamer , Tissue Engineering , Tissue ScaffoldsABSTRACT
Objective: The aim of this paper is to identify the basic organizational structure and the key elements of integrated healthcare model of patients with Chronic Obstructive Pulmonary Disease (COPD) and propose an appropriate development strategy.Methods: Based on the literature review of research articles about integrated care on patients with COPD, an analysis was conducted with the help of the Chronic Care Model (CCM) which is a chronic disease management model.Results: From of a total 16 articles about 13 case studies were found.An integrated healthcare of COPD was carried out in 10 hospital-based or community-based care programs.Most of the patients were the elderly and health status were moderately severe or more severe.The components of healthcare programs varied from 4 to 12 included at least two CCM dimension.A coordinator or a case manager was appointed in all healthcare programs and a follow-up plan was made as well.Decision making was supported by clinic guideline and specialist resource in 9 integrated healthcare programs which community facilities involved.All programs included self-management with health education and individualized behavioral support was in 10 programs.The action plan was applied in 8 studies.8 studies using a clinical information system connected health care provider and patients.Conclusions: COPD integrated care program can be constructed according to the management model of chronic disease, and it is suggested that we can organize the COPD integrated care program based on CCM and the program comprises 4 organizational components of at least two CCM dimensions.The key elements of COPD integrated healthcare are to appoint a coordinator, to make a follow-up plan, and the necessity of community participation to support decision making, support self-management by education and individualized behavioral management with an action plan.
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Calomel is a common traditional Chinese medicine (TCM) containing mercury in clinical external application. Although the toxicity of calomel has attracted concern, there is no unified standard yet in clinical external application. Risk assessment is used for evaluating the potential health effects of hazardous substances. The purpose of this article was to evaluate the health risk of calomel in clinical external application on the basis of toxicity data, to ensure safe and rational application of TCM containing calomel. The toxicity data of transdermal administration of calomel or mercurous chloride were collected by searching the literature. The daily maximum exposure dosage of calomel in clinical external application was estimated by following the four procedures of risk assessment, and Margin of Safety (MOS) as an evaluation indicator was then calculated to evaluate the safety of calomel on clinical application. It has been reported that the adult in single transdermal administration of calomel at 1. 5 g was lethal. Based on the LOAEL of calomel for long-term transdermal exposure (1 month) in rats was 0.096 g · kg(-1) · d(-1), the NOAEL of calomel for patients (about 60 kg) by external application within 2 weeks was estimated to be 1.46 mg · kg(-1) · d(-1). When MOS value equals to 1, the daily maximum exposure of calomel in clinical external application within 2 weeks was calculated to be 1.1 g. The results suggest that daily single dose of calomel in clinical external application should be lower than 1.5 g for adults, and more attention should be paid to changes in hepatic and renal function of patients when repeated dose more than 1.1 g within 2 weeks. The approach of risk assessment could be helpful in rational application of TCM containing mercury.
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Animals , Humans , Rats , Medicine, Chinese Traditional , Mercury Compounds , Toxicity , No-Observed-Adverse-Effect Level , Risk AssessmentABSTRACT
<p><b>OBJECTIVE</b>To study in vivo mercury absorption and accumulation through repeated transdermal administration of Yuhong ointment containing calomel, in order to provide scientific evidences for clinical safe medication.</p><p><b>METHOD</b>A total of 100 SD rats were randomly classified into five groups: the control group, the Yuhong ointment group, the double-concentration Yuhong Ointment group, the quadruple-concentration Yuhong ointment group and the 1.6% calomel group. The rats were treated with the dosage of 0.04 g . cm-2 by repeated transdermal administration for 2, 4 weeks. After the drug discontinuance for 4 weeks, the levels of mercury in blood, urine, and tissues of heart, liver, brain and kidney were determined, respectively.</p><p><b>RESULT</b>Compared with the control group, the blood mercury level of the Yuhong ointment group show no obvious change after treatment for 4 weeks. However, the levels of mercury in blood and urine of other experimental groups increased significantly with time and the increase in dosage, and so did the level of mercury in major organ. At 4 weeks, all experimental groups showed increase in the content of mercury, and kidneys displayed the highest level, whereas brain displayed the lowest level After the drug discontinuance for 4 weeks, the mercury level in blood and urine of every dose group recovered to normal, with significant decline in the content of mercury in each organ.</p><p><b>CONCLUSION</b>After transdermal administration in rats for 4 weeks, there was no obvious absorption of mercury in blood. Mercury was mainly accumulated in kidneys and excreted through urine. The results suggest that the patients' mercury content and kidney function indexes need to be monitored in long-term clinical use of Yuhong ointment.</p>
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Animals , Female , Male , Rats , Absorption , Drugs, Chinese Herbal , Mercury , Blood , Pharmacokinetics , Urine , Ointments , Rats, Sprague-Dawley , Safety , Time FactorsABSTRACT
<p><b>OBJECTIVE</b>To compare the efficacy of different expression vectors, target genes, and immunization procedures in transfecting mice via liposome to construct murine model of Graves disease.</p><p><b>METHODS</b>We linked pCDNA3.1(+) and pUBC to full-length human TSHR and TSHR A subunit cDNA to yield four plasmids, which were later injected intramascularly or subcutaneously into female Balb/c mice via liposome. The blood anti-TSHR antibody (TRAb) were determined and the body weight were measured after each immunization. Serum thyroid hormone levels were measured after the animals were sacrificed.</p><p><b>RESULTS</b>In mice immunized with pUBC, no significant variance with control in weight nor serum TRAb concentration was observed. Weight gain in pCDNA3.1(+) group was significantlyly slower than controls (p<0.05), and serum TRAb concentration was also significantly elevated. In pCDNA group, animals immunized with TSHR A subunit (TSHRA subgroup) as the target gene revealed even significantly slower weight gain (p<0.001) and even faster TRAb elevation than those immunized with full length TSHR. Significantly higher FT4 (p=0.023) was observed in TSHRA and TSHR subgroups, which was reversely correlated to weight gain, but no significant difference (p>0.05) in FT3 was observed. Weight gain and TRAb concentration mainly varied in the later period of immunization.</p><p><b>CONCLUSIONS</b>Immunization with pCDNA3.1(+) and TSHR A subunit gene together with higher immunization frequency increases the chance of model induction. Furthermore, FT4 is a better indicator for assessing the thyroid function in this model.</p>
Subject(s)
Animals , Female , Mice , Disease Models, Animal , Graves Disease , Genetics , Liposomes , Mice, Inbred BALB C , Receptors, Thyrotropin , Genetics , TransfectionABSTRACT
A female papillary thyroid cancer patient with diffuse micronodular pulmonary metastases was confirmed only by post radioactive iodine (RAI) therapy whole body scan (RxWBS). Her diagnostic iodine-131 whole body scan (DxWBS), chest CT and 18FDG PET/CT scan were all negative. Attention and pitfalls of this case concerning surgical and RAI dose management are against current international guidelines on thyroid cancer.