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Objective:To translate the English version of the health enhancement lifestyle profile-screener into Chinese and assess its reliability and validity based on classical test theory(CTT) and Rasch model among the elderly.Methods:A total of 447 older adults from rural and urban areas in Sichuan Province from December 2020 to March 2021 were selected by convenience sampling, and were surveyed with the revised Chinese version of health enhancement lifestyle profile-screener(HELP-CS). Rasch and CTT-based approaches were used to evaluate the unidimensionality data-model fit, internal consistency, test-retest reliability, criterion validity and discriminant validity of the questionnaire.Results:According to the results of the initial test questionnaire, the ninth question was deleted, and 14 items were retained to form a formal questionnaire. The formal test results showed that HELP-CS met the unidimensionality, and the residual mean square error for item 2 and 14 were within the acceptable range, which were 1.49 and 1.41. Item 10 and 12 had the highest logits, which were 1.87 and 1.91 respectively. There were gender differences in some topics. The Cronbach′s α of the scale was 0.719, and the test-retest reliability was 0.704 after two months. The criterion correlations with HPLP-CE were 0.581.Conclusion:HELP-CS has good adaptability, reliability and validity in the elderly, and can be used as a quick and effective screening tool in the study of the lifestyle of the elderly.
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Objective To explore the effects of irbesartan combined with hemodialysis on renal function,inflammatory factors and renal hemodynamics in patients with renal proteinuria.Methods A total of 106 patients with renal proteinuria who underwent hemodialysis in Changzheng Hospital Affiliated to Naval Medical University from May 2016 to May 2018 were selected for the study and were divided into observation group and control group according to the random number table method.The two groups were given hemodialysis,and observation group was given irbesartan on this basis.Kidney-related examination indexes [24 h urine protein quantitation,24 h urine volume,serum creatinine (Scr),urea nitrogen (BUN)],inflammatory factors [C-reactive protein (CRP),interleukin-8 (IL-8),intercellular adhesion molecule-1 (ICAM-1),monocyte chemoattractant protein-1 (MCP-1)],bilateral renal interlobar artery resistance index (RI),hemorheology (whole blood viscosity,low-shear viscosity,high-shear viscosity,erythrocyte aggregation index)were observed in the two groups before and after treatment.Results After 3 months of treatment,the levels of urine protein quantitation,serum Scr,BUN,CRP,IL-8,ICAM-1 and MCP-1 in the two groups were lower than those before treatment,and the levels in observation group were lower than those in control group (P ＜ 0.05);the 24h urine volume was more than that before treatment,and the level in observation group was more than that in control group (P ＜ 0.05).The RI values of bilateral kidney in the two groups were lower than those before treatment,and the value in observation group was lower than that in control group (P ＜ 0.05).The whole blood viscosity,low-shear viscosity,high-shear viscosity and erythrocyte aggregation index in the two groups were lower than those before treatment,and the indexes in observation group were lower than those in control group (P ＜ 0.05).Conclusions Addition of irbesartan in patients with renal proteinuria treated by hemodialysis can effectively improve renal function,reduce inflammation and blood viscosity,and improve renal hemodynamics,and promote the disease outcomes.
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Cerasomes with different shapes were constructed to investigate the effect of the nanocarriers' shape on the cellular uptake and transmembrane capacity. Cerasome-forming lipid (CFL) was synthesized via halogenation, nucleophilic addition and acylation reaction and detected by mass spectrometry and nuclear magnetic resonance spectroscopy. CFL and short chain 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) were employed to prepare organic-inorganic hybrid bicelles in discal shapes (nanodisc) by the thin-film hydration method, and CFL was also used to prepare spherical cerasomes (nanosphere). The particle size and zeta potential of nanocarriers were measured by dynamic light scattering analysis, and the morphology was observed by transmission electron microscopy. With human colon cancer cell line Caco-2 as the model, the effect of the shape of nanocarriers on cellular uptake and transmembrane capacity was investigated qualitatively by confocal laser scanning microscope (CLSM), and the transmembrane capacity was analyzed quantitatively by high performance liquid chromatography (HPLC). The results showed that nanosphere and nanodisc had similar particle diameters around 110 nm and similar zeta potential around -25 mV, with regular morphology under transmission electron microscope. The cellular uptake rate of nanodisc was significantly higher than that of nanosphere in 20 minutes. Further research on Caco-2 cell monolayer demonstrated that nanodisc with faster uptake had less accumulation in the monolayer, which means it had a higher transmembrane rate on Caco-2 cell monolayer and the transmembrane capacity of the nanodisc was better than that of nanosphere within 2 h. These results suggest that rational design of the shape of nanocarriers is expected to regulate nano-bio interactions, promote the transmembrane transport of nanocarriers, and improve the drug absorption.
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OBJECTIVE：To evaluate the cost-effectiveness between Mycophenolate mofetil （MMF）dispersible tablets versus MMF capsules for the immunosuppressive therapy after renal transplantation ，and to provide reference for selecting more economical MMF preparations. METHODS ：Based on a systematic review about MMF dispersible tablets and MMF capsules for immunosuppressive therapy after renal transplantation （involving 6 clinical studies ），with simulation period of 6 months，Treeage 2010 software was used to establish decision tree model ，which included four states of graft normal ，acute rejection ，graft loss and death. Using QALYs as effect measurement index ，the cost-effectiveness analysis of two MMF preparations was carried out in combination with the cost data of West China Hospital of Sichuan University. Signal factor sensitivity analysis and probability sensitivity analysis were performed . RESULTS ：The incremental cost-effectiveness ratio of MMF capsules group to MMF dispersible tablets group was 623 111.614 0 yuan/QALY，which was higher than Chinese willing-to-pay value （212 676 yuan/QALY）；the results of sensitivity analysis supported the above results. CONCLUSIONS ：MMF dispersible tablets are better than MMF capsules in cost-effectiveness of immunosuppressive therapy after renal transplantation.
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OBJECTIVE：To evaluate the efficacy and s afety of different administration routes of bevacizumab in the treatment of malignant pleural effusion （MPE），and to provide evidence-based reference for rational use of drugs in clinic. METHODS ： Retrieved from Cochrane L ibrary，PubMed，Embase，VIP，CNKI，Wanfang database and CBM ，clinical studies were collected ， about bevacizumab combined with or without chemotherap eutic drugs （trial group ）versus chemotherap eutic drugs （control group ） in the treatment of MPE under different administration routes. After literature screening and data extraction ，the quality of RCTs was evaluated by using bias risk evaluation tool recommended by Cochrane Systematic Evaluator Manual 5.3. Newcastle-Ottawa scale was used to evaluate the quality of the retrospective study. Meta-analysis was performed by using Rev Man 5.3 software， network Meta-analysis was performed by using Stata 13.0 software and intervention measures were ranked by using R 3.6.1 software. RESULTS ：A total of 29 studies were included ，involving 21 RCTs and 8 retrospective studies ，including 2 254 patients. The studies involved 5 intervention measures ，such as bevacizumab+chemotherap eutic drugs （thoracic perfusion ），bevacizumab+ chemotherapeutic drugs （ivgtt），bevacizumab（thoracic perfusion ），chemotherapeutic drugs （thoracic perfusion ），chemotherapeutic drugs（ivgtt）. Network Meta-analysis showed there was no statistical significance in bevacizumab+chemotherap eutic drugs （thoracic perfusion）and bevacizumab+chemotherap eutic drugs （ivgtt）[OR＝0.81，95％CI（0.13，4.60），P＞0.05]，chemotherapeutic drugs （thoracic perfusion ）and chemo therapeutic drugs （ivgtt）[OR＝ 0.47， 95％ CI （0.07，3.10）， P＞0.05]， bevacizumab + Z19SCHX202） chemotherapeutic drugs （ivgtt） and chemotherap eutic drugs （ivgtt） [OR＝0.56，95％ CI（0.27，1.20），P＞0.05]. Total 、 response rate of bevacizumab + chemotherap eutic drugs （thoracic perfusion ） [OR＝3.10，95％ CI（2.10，4.50），P＜ 0.05]，bevacizumab（thoracic perfusion ）[OR＝1.90，95％CI （0.99，3.90），P＜0.05] were significantly higher than chemotherapeutic drugs （thoracic perfusion ）. Network Meta-analysis ranking showed that bevacizumab + chemotherapeutic drugs （ivgtt）＞ bevacizumab + chemotherapeutic drugs （thoracic perfusion ）＞ bevacizumab（thoracic perfusion ）＞chemotherapeutic drugs （ivgtt）＞chemotherapeutic drugs （thoracic perfusion ）. The incidence of elevated blood pressure [RR= 2.64，95％CI（1.56，4.43），P＝0.000 3] and proteinuria [RR ＝3.24，95％CI（1.79，5.86），P＝0.000 1] in trial group were significantly higher than control group. There was no statistical significance in the incidence of granulo- cytopenia [RR ＝0.94，95％CI（0.81，1.09），P＝0.41] or nausea and vomiting [RR ＝0.87，95％CI（0.73，1.03），P＝0.10] between 2 groups. Compared with chemotherapy alone ，bevacizumab combined chemotherapy could not prolong the total survival time of patients，but can improve the progression-free survival time. CONCLUSIONS ：Bevacizumab combined with chemotherapy can improve the efficacy of MPE patients ，but thoracic perfusion can increase the risk of proteinuria and elevated blood pressure.
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OBJECTIVE：To provide reference for choosing a more economical first-line treatment for advanced or recurrent squamous cell NSCLC and reducting patients ’cost burden. METHODS ：Based on a published high-quality phase Ⅲ randomized clinical controlled trial ，Markov model was established according to the disease development process. The disease development process of patients with squamous cell NSCLC was divided into non-progressive free survival state ，disease progress state and death state. The cost-effectiveness analysis of ND regimen containing nedaplatin and CD regimen containing cisplatin was carried out on the basis of the treatment cost data of our hospital. The uncertainty of the results was evaluated with single factor sensitivity analysis and probability sensitivity analysis. RESULTS ：According to the results of analysis Markov model ，the cost-effectiveness in ND regimen was 54 995.58 yuan/QALYs，in CD regimen was 50 274.36 yuan/QALYs，and incremental cost-effectiveness ratio was 86 327.27 yuan/QALYs，which was lower than the willing payment threshold （193 932.00 yuan/QALYs）. The results of single factor sensitivity analysis showed that non-progressive free survival of patients accepted two regimens had the greatest influence on the cost-effectiveness analysis results. The probability sensitivity analysis showed that with the increase of per capita GDP in China ， the probability of cost-effectiveness of ND regimen increased gradually. CONCLUSIONS ：Compared with CD regimen ，ND regimen is more cost-effective in the treatment of advanced or recurrent squamous cell NSCLC.
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Objective To compare the effect and safety of stenting versus directional atherectomy (DA) in the treatment of TASCⅡ A and B superficial femoral artery lesions.Methods 100 patients with TASC Ⅱ A and B lesions were divided into percutaneous transluminal stenting(PTS) group (n =50) and DA group (n =50).Patients were compared in terms of technical success rate,treatment success rate,first operation cost,postoperative ankle brachial index (ABI),limb salvage rate,survival,and patency.Results The technical success rate in both PTS and DA group was 100％.The treatment success rate was 98％ vs.86％,P＞0.05.Postoperative ABI:0.82 ±0.19 vs.0.80 ±0.27,P＞0.05.First operation cost:(34 820 ± 1 051) yuan vs.(45 635 ± 1 358) yuan,P ＜0.001;All patients were followed-up for up to 2-year,the cumulative patency rate was 81.6％ vs.72.9％ (P＞0.05).Limb salvage rate was 97.9％ vs.93.8 ％,P ＞ 0.05.Conclusion There were no significant differences in the effect and safety of PTS versus DA in the treatment of TASCⅡ A and B superficial femoral artery lesions.
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OBJECTIVE: To investigate the effect of different interfaces on FiO_2 and CO_2 rebreathing(ViCO_2) during noninvasive positive pressure ventilation. METHODS: The Active Servo Lung respiratory simulation system was used to simulate a hypercapnia COPD patient received NPPV through injection of CO_2 gas from the place closest to the outlet of simulated lung to maintain end-tidal carbon dioxide partial pressure at 80 mmHg,and oxygen delivery during NPPV was simulated by means of injection of 5 L/min oxygen through the hole of interface. FiO_2 and ViCO_2 were integral calculated through the synchronous collect real-time pressure, flow rate, oxygen concentration and CO_2 concentration. The effect of different type and models of interfaces on FiO_2 and ViCO_2 were compared, and the bivariate correlation analysis was applied to investigate the correlation of FiO_2 and ViCO_2. RESULTS: The inner volume, leak volume and leak position of different interfaces were different. The FiO_2 of the oral-nasal mask and nasal mask were significantly different(P<0.05), which were(39.81±9.06)% and(43.91±6.33)%,respectively. The FiO_2 of the different models of interfaces was significantly different(P<0.05), the FiO_2 of the No.4 oral-nasal mask was the lowest(28.29±0.08)%, and the FiO_2 of the No. 10 oral-nasal mask was the highest(53.83±0.63)%. The ViCO_2 of the oral-nasal mask and nasal mask wasn't significantly different(P=0.19), which was(15.26±1.27)mL and(14.79±2.21)mL, respectively. The ViCO_2 of the different models of interfaces was significantly different(P<0.05), the FiO_2 of the No.8 nasal mask was the lowest(12.48±0.29%), and the ViCO_2 of the No. 10 nasal mask was the highest(18.38±0.31)%. There was a significant correlation between FiO_2 and ViCO_2(r=0.41, P<0.05), and the general linear equation was Y=14.51+1.82 X(R~2=0.168). CONCLUSION: Different interfaces have significant effects on FiO_2 and ViCO_2 during NPPV,and FiO_2 and ViCO_2 are positively correlated.
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Intermedin/adrenomedullin-2 (IMD/AM2), a member of the calcitonin gene-related peptide/AM family, plays an important role in protecting the cardiovascular system. However, its role in the enhanced sympathoexcitation in obesity-related hypertension is unknown. In this study, we investigated the effects of IMD in the paraventricular nucleus (PVN) of the hypothalamus on sympathetic nerve activity (SNA), and lipopolysaccharide (LPS)-induced sympathetic activation in obesity-related hypertensive (OH) rats induced by a high-fat diet for 12 weeks. Acute experiments were performed under anesthesia. The dynamic alterations of sympathetic outflow were evaluated as changes in renal SNA and mean arterial pressure (MAP) in response to specific drugs. Male rats were fed a control diet (12% kcal as fat) or a high-fat diet (42% kcal as fat) for 12 weeks to induce OH. The results showed that IMD protein in the PVN was downregulated, but Toll-like receptor 4 (TLR4) and plasma norepinephrine (NE, indicating sympathetic hyperactivity) levels, and systolic blood pressure were increased in OH rats. LPS (0.5 µg/50 nL)-induced enhancement of renal SNA and MAP was greater in OH rats than in obese or control rats. Bilateral PVN microinjection of IMD (50 pmol) caused greater decreases in renal SNA and MAP in OH rats than in control rats, and inhibited LPS-induced sympathetic activation, and these were effectively prevented in OH rats by pretreatment with the AM receptor antagonist AM22-52. The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) inhibitor U0126 in the PVN partially reversed the LPS-induced enhancement of SNA. However, IMD in the PVN decreased the LPS-induced ERK activation, which was also effectively prevented by AM22-52. Chronic IMD administration resulted in significant reductions in the plasma NE level and blood pressure in OH rats. Moreover, IMD lowered the TLR4 protein expression and ERK activation in the PVN, and decreased the LPS-induced sympathetic overactivity. These results indicate that IMD in the PVN attenuates SNA and hypertension, and decreases the ERK activation implicated in the LPS-induced enhancement of SNA in OH rats, and this is mediated by AM receptors.
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Animals , Male , Adrenomedullin , Metabolism , Blood Pressure , Physiology , Hypertension , Lipopolysaccharides , Pharmacology , Neuropeptides , Metabolism , Obesity , Rats, Sprague-Dawley , Receptors, Adrenomedullin , Metabolism , Sympathetic Nervous System , Metabolism , Toll-Like Receptor 4 , MetabolismABSTRACT
CY-1-4 is a tryptanthrin derivative exhibiting antitumor activity. The solubility of CY-1-4 was poor and the corresponding mechanism needs further study. To solve this problem, we prepared nanoparticles encapsulated with CY-1-4 (CY-1-4 NPs) by nanoprecipitation method using poly(caprolactone) (PCL) and poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) as carriers to improve solubility. We then explored whether CY-1-4 NPs induced B16-F10 cytotoxicity via ferroptosis by determining the effect of CY-1-4 NPs on reactive oxygen (ROS) levels, repairing efficacy of lipid reactive oxygen inhibitor ferrostatin-1 and iron chelator deferoxamine (DFO), and potentiation of protoporphyrin (PPIX) induced B16-F10 cell death. The results showed that nanoparticlated strategy significantly improved solubility of CY-1-4. With the particle size about 116 nm, encapsulating efficacy was about 83% and the drug loading capacity was about 4.80%. Ferroptosis mechanistic studies indicated that CY-1-4 NPs could improve the ROS level in B16-F10 cells, whereas ferrostatin-1 and DFO could partly inhibited the cytotoxicity and PPIX could potentiated the cytotoxicity of CY-1-4 NPs in B16-F10 cells. These results showed that ferroptosis was one of the cell death mechanisms induced by tryptanthrin derivative CY-1-4 nanoparticle.
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Objective To establish an HPLC method for the content determination of morroniside, sweroside, paeoniflorin and loganin of Liuwei Dihuang Decoction and its Cornus Officinalis-Cortex Moutan couple; To discuss the relationship between the whole prescription and the couple of main pharmacodynamic components. Methods The HPLC method was used at Hypersile C18 column (4.6 mm × 250 mm, 5 μm); the mobile phase consisted of methanol-water (24:76); the detective wavelength was 236 nm; the flow rate was 1.0 mL/min; the column temperature was 30 ℃. Results The linear ranges of morroniside, sweroside, paeoniflorin and loganin were among 0.480–7.680 μg (r=0.999 3), 0.103–1.650 μg (r=0.999 5), 0.120–1.920 μg (r=0.999 1) and 0.227–3.630 μg (r=0.999 7), respectively. The average recovery rates and RSD were 102.79%, 102.29%, 100.99%, 102.48%, and 1.73%, 1.48%, 1.32%, 0.75%, respectively. The contents of morroniside, sweroside and paeoniflorin in Liuwei Dihuang Decoction were slightly higher than that in Cornus Officinalis - Cortex Moutan couple, and the contents of loganin were almost the same. Conclusion The method is simple, stable, accurate and reproducible. It can be used for content determinate of glycosides in Liuwei Dihuang Decoction and Cornus Officinalis-Cortex Moutan couple. Cornus Officinalis-Cortex Moutan couple has the glycosides with tonifying kidney effect of Liuwei Dihuang Decoction.
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Objective:To investigate interleukin-32 (IL-32)(rs28372698A/T,rs12934561C/T and rs11861531C/T) genetic susceptibility in patients with multiple sclerosis(MS)by case-control study,which provides a theoretical foundation for high-risk population with MS.Methods:A total 580 MS patients and 650 healthy controls were included in this study,polymerase chain reaction-single base extension (PCR-SEB) was used to test DNA sequencing,and serum levels of IL-32 were determined by enzyme-linked im-munosorbent assay.Results:The genotype and allele frequency of IL-32 (rs28372698A/T) had significantly differences compared with healthy controls (P=0.007,P=0.033),however,there were no statistical differences in rs12934561C/T and rs11861531C/T between the two groups (P>0.05).T-T-T haploid genotype in patients with MS was higher than control groups(P=0.012),and T-T-T haploid genotype was associated with increased risk of MS(OR=1.968,95% CI:1.968-1.352).Serum levels of IL-32 in patients with MS was increased compared with control groups[(399.08 ± 156.85)pg/ml vs (239.99 ± 88.35)pg/ml,P= 0.001].The serum IL-32 concentrations in MS patients with AT and TT genotype were higher compared with MS patient with AA genotype[(465.53±172.40) pg/ml vs(295.86±103.96)pg/ml,P<0.01;(491.15±133.65)pg/ml vs(295.86±103.96)pg/ml,P<0.01].Conclusion:Our study found that an association between IL-32(rs28372698) gene polymorphism and MS,and serum levels of IL-32 were influenced by IL-32 gene polymorphism in patients with MS,suggesting a theoretical basis for individualized diagnosis and treatment of MS patients.
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Objective To set up a favorable animal model for the drug treatment research of endometriosis by establishing the animal model of endometriosis in SCID and nude mice so as to compare the influences on implantation of human endometrial tissue derived from the eutopic and ectopic sources. Methods Eutopic and ectopic endometrium were transplanted to the lower abdominal parts subcutaneously of 30 sexually matured BALB/c-nu/nu nude mice and SCID mice respectively. The ectopic lesion sizes were under the regular observation before they were removed 6 weeks after the operation for pathological examinations. Results Nude mice and SCID mice were able to be used to establish a successful animal models of endometriosis. The success rate of SCID mice was higher than that of nude mice. The success rate of the eutopic endometrium group was significantly higher than that of the ectopic endometrium group. Nude and SCID mice endometriosis implantation models were successfully established. The modeling success rate of SCID mice is higher than that of the nude mice.The success rate of transplantation was higher in the ectopic endometrium than in the eutopic endometrium.Conclusion The SCID mice endometriosis endometriosis model provides a favorable animal model of endometriosis.
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Long non-coding RNA plays an important regulatory role in life activities of organisms and is widely involved in the pathological and physiological processes of organisms.Abnormal expression of long noncoding RNA also frequently occurrs in some inflammatory diseases.In these diseases,there may be excessive inflammatory damage,or an imbalance in the immune response.Bronchial asthma is a typical airway inflammatory disease,and the imbalance of immune response plays an essential role in its development.Long non-coding RNA may be involved in the regulation of the pathogenesis of asthma through the dual mechanism of innate and adaptive immunity.This review summarizes the immune-inflammatory regulation mechanism of long non-coding RNA and its preliminary research progresses in asthma.
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In this study, we developed a rapid and sensitive ultra high-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS) method to detect a sulfide bond doxorubicin conjugation prodrug (DOX-S-DOX) in human breast cancer tumor cells (MCF-7). The samples were prepared by acetonitrile precipitation using daunorubicin as internal standard (IS). A reversed phase C18 analytical column (Agilent Eclipse plus C18 RRHD 1.8 μm, 2.1 mm×50 mm) was utilized to separate the samples under gradient elution conditions. Mobile phase was a mixture of 0.1% formic acid in water and methanol at a flow rate of 0.4 mL ·min-1. The analysis was conducted on the mass spectrometer using an electrospray interface (ESI) in the positive ionization model. The calibration range was 20.0-400 ng·mL-1 with the correlation coefficients (r2) ≥ 0.99. The inter-and intra-assay precision (relative standard deviation, RSD%) of quality control samples was within 3.77%-8.35% and relative error (RE%) for accuracy was between -2.04% and 2.62%. Recovery (97.67%-104.2%) and matrix effect (104.8%-113.9%) were consistent, precise, and reproducible at different quality control levels in accordance with FDA guidance. The assay was successfully used in the cellular pharmacokinetics study of DOX-S-DOX, which may provide a clue to explore analytical methods of other prodrug forms of DOX.
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Objective To compare the difference of mortality risk between patients undergoing nocturnal hemodialysis (NHD) and conventional hemodialysis (CHD) and to explore the related factors of mortality.Methods The study cohort comprised the maintenance hemodialysis patients receiving either NHD (n=111) or CHD (n=722) in Changzheng Hospital of Second Military Medical University from Feb.2009 to Feb.2017.The demographic information,clinical characteristics,survival status,causes of death and laboratory examination indexes were obtained from hemodialysis management system.The urea clearance index (Kt/V),hemoglobin,blood phosphorus concentration and mortality were compared between NHD and CHD patients.The multivariate-adjusted Cox model was used to analyze the mortality risk of all patients.Results Compared with the patients receiving CHD,the proportion of male was more in the NHD group,and the baseline age was younger (P＜0.01) and baseline dialysis vintage was longer (P＜0.01).There was no significant difference in incidences of primary disease and comorbidities,or laboratory examination results.Compared with the CHD group,the levels of Kt/V and hemoglobin in the NHD group were significantly higher (P＜0.01),and the blood phosphorus concentration was significantly lower (P＜0.05).Mortality in the NHD and CHD groups was 3.5 per 100 patients-years and 6.2 per 100 patients-years,respectively.After the adjustment by baseline age,dialysis vintage,gender,and comorbidities,Cox model analysis showed that the mortality risk in the NHD group was lower than in the CHD group (HR=0.67,95％CI:0.39-1.00,P=0.05).Subgroup analysis showed NHD was of more survival benefit for male (P＜0.05),non-diabetic patients (P =0.05) and patients with conventional dialysis vintage ＞3 years (P＜0.05).Conclusion NHD can effectively increase the solute clearance,improve anemia and calcium and phosphate metabolism,and thus reduce the mortality risk of maintenance hemodialysis patients.
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The difference in pH between apical and basolateral side of intestinal epithelial and pH dependence character of the combination of FcRn (neonatal Fc receptor) and ligand might improve the delivery of hydrophobic drugs by facilitating the transcytosis of nanocarriers. Here we designed FcBP (IgG Fc domain-binding peptides) decorated coumarin 6 (C6) loaded poly(ethyl ethylene phosphate)-co-poly(ε-caprolactone) (PEG-PCL) micelles with different ligand densities to study the effect of pH and ligand density on the endocytosis and exocytosis process of micelles on human colon adenanocaricinoma cell lines (Caco-2). Active micelles with different ligand densities and passive micelles were prepared using the thin-film hydration method. The size of the micelles was characterized by dynamic light scattering analysis and the morphology was observed by transmission electron microscope. The endocytosis and exocytosis of the micelles at pH 7.4 and pH 6.0, as well as the effect of FcRn on the endocytosis, were investigated by flow cytometry. The results showed that the size of micelles was about 30 nm, which was not affected by FcBP decoration. We found that pH and ligand density could both influence the endocytosis. The uptake of active micelles was higher at pH 6.0 than at pH 7.4, and an optimal ligand density of endocytosis was appeared in both pH environment. Then we proved that FcBP decorated micelles could be endocytosed at pH 6.0 and exocytosed at pH 7.4, and the exocytosis process was also related to ligand density. Micelles with 10% ligand density had the largest exocytosis, showing the potentiality to deliver drugs through the intestinal epithelial. In addition, the competitive inhibition experiments illustrated that the interaction between FcRn and FcBP were essential to endocytosis. The results will enhance the understanding on the FcBP decorated PEG-PCL micelles for transmemberane drug delivery.
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Objective To establish a mouse model of kidney-yin and kidney?yang deficiency after oral administra?tion of hydrocortisone, and to explore the related evaluation factors. Methods The model was established by oral adminis?tration of hydrocortisone to induce kidney?yin and kidney?yang deficiency in mice. The survival and body weight of the mice were observed. The serum content of adrenal cortical hormone ( ACTH) , cortisol ( Cor. ) in the hypothalamic?pituitary?ad?renal (HPA) axis, and thyroid stimulating hormone (TSH), triiodothyronine (T3), thyrox (T4) in the hypothalamic?pi?tuitary?thyroid (HPT) axis, follicle?stimulating hormone (FSH), estradiol (E2), testosterone (T) in the hypothalamic?pituitary?gonadal ( HPG) axis were determined by radioimmunoassay. Results The body weight of kidney?yin and kidney?yang mice were decreased, the serum ACTH, Cor, TSH, T3, T4 contents were decreased, the serum FSH, E2, T contents were increased in the kidney?yang deficiency model mce ( P<0. 01 ) , and those parameters in the kidney?yin deficiency model mice were changed in opposite direction. Conclusions It is found that the hormone levels of ACTH, Cor, TSH, T3, T4, FSH, E2 and T in kidney deficiency mice are changed, and cortisol can be used as an important index to evaluate the model of kidney deficiency induced by glucocorticoid.
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AIM:R-spondin 2 (Rspo2), one member of R-spondin family which contains four secreted proteins , plays an important role in skeletal muscle development .However, the impact of Rspo2 on vascular smooth muscle cell ( SMC) differentiation is little known . This study aims at revealing the role and mechanism of Rspo 2 on SMC differentiation from embryonic stem cells (ESCs).METHODS:A well-established model for studying SMC differentiation from ESCs were used , in which mouse embryonic stem cells ( ES-D3) were seeded on collagen IV-coated flasks and cultured in differentiation medium (DM) for 2, 4, 6 and 8 days.Smooth muscle specific markers, includingα-smooth muscle actin (α-SMA), SM22 and smooth muscle myosin heavy chain (SM-MHC), were detected to in-sure the successful model by qRT-PCR and Western blot .After 3-day pre-differentiation, ESCs were treated with recombinant Rspo 2 protein, overexpression plasmid or shRNA plasmid for 96 h, and the mRNA and protein expression of smooth muscle markers was detected.To explore the role of Rspo2 on SMC differentiation in vivo, 3-day predifferentiated ESCs (106 in 50μLα-MEM) incubated with Rspo2-overexpression plasmid were mixed with 50 μL of Matrigel ( Becton Dickinson Labware ) and then subcutaneously injected into C57BL/6J mice.After 12 days, mice were sacrificed and the implants were harvested for immunofluorescence staining , qRT-PCR and Western blot.Furthermore, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation assay (ChIP) and lucif-erase reporter assay were performed to investigate the transcriptional activity of SMC differentiation related transcription factors , inclu-ding serum response factor (SRF), myocardin (MYO), myocyte-specific enhancer factor 2C (MEF-2C).Involvement of Rspo2 re-ceptor, leucine-rich repeat-containing, G-protein-coupled receptors (Lgr)4,5,6, and β-catenin pathway during Rspo2-induced MSC differentiation were also uncovered by overexpression or inhibition of the respective protein .RESULTS:Our results showed that Rspo 2 mRNA and protein expression was significantly and consistently increased during ESC differentiation towards SMCs .Recombinant Rs-po2 protein and enforced Rspo 2 expression in ESCs resulted in up-regulation of smooth muscle markers and transcription factors , while knockdown decreased the expression of these genes .Expectedly , Rspo2 overexpression also promotes SMC differentiation in vivo. Mechanistically , our data showed that Rspo 2 could promote SRF binding to SM22 promoter region .Evidence also revealed that one of three Rspo2 receptors, LGR5, was up-regulated while the other two , LGR4 and LGR6, was down-regulated.Silencing of LGR5 inhibi-ted Rspo2-induced SMC differentiation, whereas knockdown of LGR4 had no impact.Finally, activation or inhibition of β-catenin could promote or inhibit SMC differentiation , respectively .CONCLUSION: Our findings demonstrate for the first time that Rspo 2 plays a positive role during smooth muscle cell differentiation from embryonic stem cells .We confirmed that Rspo 2 can up-regulate smooth muscle markers at transcription level .We also revealed Rspo promote smooth muscle cell differentiation through activation of LGR 5 re-ceptor and Wnt/β-catenin pathway .
ABSTRACT
The integrity of poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) micelles transcellular transported across madin-darby canine kidney (MDCK) epithelial cells was investigated. Fluorescein isothiocyanate isomer I (FITC) was conjugated to PEG-PCL and the product PEG-PCL-FITC was identified by fluorescence spectra. Two micelles were prepared using the thin-film hydration method:3,3'-dioctadecyloxacarbocyanine perchlorate (DiO) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) co-loaded PEG-PCL micelles (DiO-DiI-M), DiI loaded and PEG-PCL-FITC contained micelles (FITC-DiI-M). The size of the micelles was characterized by dynamic light scattering analysis using a Malvern Zetasizer Nano ZS and it turned out that the particle sizes of both micelles were about 30 nm with identical polydispersity index (PDI). The stability of the micelles in phosphate buffer saline (PBS) was monitored using fluorescence spectra and both micelles were stable within 4 h in PBS. The integrity of PEG-PCL micelles in the transcellular process across MDCK epithelial cell monolayer at 1 and 4 h was investigated using laser confocal scanning microscope and Förster resonance energy transfer (FRET) technology. The Person's coefficient and FRET efficiency of both Transwell layer and Receive layer were recorded. The results show that the FRET efficiency and Person's coefficient of the Receive layer was consistent with that of Transwell layer for both the micelles at 1 h, but decreased at 4 h and FITC-DiI-M decreased more significantly than DiO-DiI-M. The results indicated that the micelles could transport across the MDCK monolayer intactly at 1 h but some of them were disassembled during the 4 h transportation process.