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BACKGROUND: Salt-sensitive hypertension is often more prone to induce damage to target organs such as the heart and kidneys. Abundant recent studies have demonstrated a close association between ferroptosis and cardiovascular diseases.Therefore, we hypothesize that ferroptosis may be closely associated with organ damage in salt-sensitive hypertension. This study aimed to investigate whether ferroptosis is involved in the occurrence and development of myocardial fibrosis and renal fibrosis in salt-sensitive hypertensive rats. METHODS: Ten 7-week-old male Dahl salt-sensitive (Dahl-SS) rats were adaptively fed for 1 week, then randomly divided into two groups and fed either a normal diet (0.3% NaCl, NDS group) or a high-salt diet (8% NaCl, HDS group) for 8 weeks. Blood pressure of the rats was observed, and analysis of the hearts and kidneys of Dahl-SS rats was conducted via HE-staining, Masson-staining, Prussian-blue-staining, TEM, tissue iron content detection, MDA content detection, immunofluorescence, and Western blot. RESULTS: Compared to the NDS group, rats in the HDS group increases in systolic blood pressure(SBP) and diastolic blood pressure(DBP)(P<0.05);collagen fiber accumulation was observed in the heart and kidney tissues (P<0.01), accompanied by alterations in mitochondrial ultrastructure,reduced mitochondrial volume, and increased density of the mitochondrial double membrane. Additionally,there were significant increases in both iron content and MDA levels(P<0.05). Immunofluorescence and Western blot results both indicated significant downregulation (P<0.05) of xCT and GPX4 proteins associated with ferroptosis in the HDS group. CONCLUSION: Ferroptosis is involved in the damage and fibrosis of the heart and kidney tissues in salt-sensitive hypertensive rats.
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BACKGROUND: Vessels encapsulating tumor clusters (VETC) represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma (HCC). However, it seems that no one have focused on predicting VETC status in small HCC (sHCC). This study aimed to develop a new nomogram for predicting VETC positivity using preoperative clinical data and image features in sHCC (≤ 3 cm) patients. AIM: To construct a nomogram that combines preoperative clinical parameters and image features to predict patterns of VETC and evaluate the prognosis of sHCC patients. METHODS: A total of 309 patients with sHCC, who underwent segmental resection and had their VETC status confirmed, were included in the study. These patients were recruited from three different hospitals: Hospital 1 contributed 177 patients for the training set, Hospital 2 provided 78 patients for the test set, and Hospital 3 provided 54 patients for the validation set. Independent predictors of VETC were identified through univariate and multivariate logistic analyses. These independent predictors were then used to construct a VETC prediction model for sHCC. The model's performance was evaluated using the area under the curve (AUC), calibration curve, and clinical decision curve. Additionally, Kaplan-Meier survival analysis was performed to confirm whether the predicted VETC status by the model is associated with early recurrence, just as it is with the actual VETC status and early recurrence. RESULTS: Alpha-fetoprotein_lg10, carbohydrate antigen 199, irregular shape, non-smooth margin, and arterial peritumoral enhancement were identified as independent predictors of VETC. The model incorporating these predictors demonstrated strong predictive performance. The AUC was 0.811 for the training set, 0.800 for the test set, and 0.791 for the validation set. The calibration curve indicated that the predicted probability was consistent with the actual VETC status in all three sets. Furthermore, the decision curve analysis demonstrated the clinical benefits of our model for patients with sHCC. Finally, early recurrence was more likely to occur in the VETC-positive group compared to the VETC-negative group, regardless of whether considering the actual or predicted VETC status. CONCLUSION: Our novel prediction model demonstrates strong performance in predicting VETC positivity in sHCC (≤ 3 cm) patients, and it holds potential for predicting early recurrence. This model equips clinicians with valuable information to make informed clinical treatment decisions.
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Background: The aim of the study is to demonstrate that radiomics of preoperative multi-sequence magnetic resonance imaging (MRI) can indeed improve the predictive performance of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods: A total of 206 patients with pathologically confirmed HCC who underwent preoperative enhanced MRI were retrospectively recruited. Univariate and multivariate logistic regression analysis identified the independent clinicoradiologic predictors of MVI present and constituted the clinicoradiologic model. Recursive feature elimination (RFE) was applied to select radiomics features (extracted from six sequence images) and constructed the radiomics model. Clinicoradiologic model plus radiomics model formed the clinicoradiomics model. Five-fold cross-validation was used to validate the three models. Discrimination, calibration, and clinical utility were used to evaluate the performance. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to compare the prediction accuracy between models. Results: The clinicoradiologic model contained alpha-fetoprotein (AFP)_lg10, radiological capsule enhancement, enhancement pattern and arterial peritumoral enhancement, which were independent risk factors of MVI. There were 18 radiomics features related to MVI constructed the radiomics model. The mean area under the receiver operating curve (AUC) of clinicoradiologic, radiomics and clinicoradiomics model were 0.849, 0.925 and 0.950 in the training cohort and 0.846, 0.907 and 0.933 in the validation cohort, respectively. The three models' calibration curves fitted well, and decision curve analysis (DCA) confirmed the clinical usefulness. Compared with the clinicoradiologic model, the NRI of radiomics and clinicoradiomics model increased significantly by 0.575 and 0.825, respectively, and the IDI increased significantly by 0.280 and 0.398, respectively. Conclusions: Radiomics of preoperative multi-sequence MRI can improve the predictive performance of MVI in HCC.
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The fall armyworm, Spodoptera frugiperda (Noctuidae: Lepidoptera), is a wide-reaching notorious insect pest of important cereal crops, which has developed resistance to multiple classes of insecticides. It invaded the Sichuan Province of China in 2019. In this study, we performed resistance monitoring of insecticides for 11 field-collected populations from Sichuan, and all the populations were susceptible to emamectin benzoate and chlorpyrifos. The variations in resistance level to indoxacarb (resistance ratio (RR), 9.23-45.53-fold), spinetoram (RR, 4.32-18.05-fold), and chlorantraniliprole (RR, 2.02-10.39-fold) were observed among these populations. To investigate the resistance mechanism of chlorantraniliprole, synergism tests were performed and showed that piperonyl butoxide had a slight synergistic effect on chlorantraniliprole for the QJ-20 population (1.43-fold) in moderate resistance (RR, 10.39-fold) compared with the treatment group without synergist. Furthermore, the expression scanning for resistance-related genes showed that five P450 genes (CYP6AE43, CYP321A8, CYP305A1, CYP49A1, and CYP306A1) and the ryanodine receptor gene (Ryr, chlorantraniliprole target) were overexpressed in the QJ-20 population. These results indicated that the fall armyworm in Sichuan has exhibited diverse susceptibilities to several classes of insecticides, and the overexpression of Ryr and several P450 genes may contribute to the development of resistance in S. frugiperda to chlorantraniliprole.
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BACKGROUND: Both diabetic and hypertensive nephropathy eventually progress to glomerulosclerosis. Previous studies revealed a potential role of endothelial-to-mesenchymal transition (EndMT) in the pathophysiology of glomerulosclerosis in diabetic rats. Therefore, we hypothesized that EndMT was also involved in the development of glomerulosclerosis in salt-sensitive hypertension. We aimed to explore the effects of high-salt diet on endothelial-to-mesenchymal transition (EndMT) in glomerulosclerosis in Dahl salt-sensitive (Dahl-SS) rats. METHODS: Eight-week-old male rats were fed high-salt (8%NaCl; DSH group) or normal salt (0.3%NaCl; DSN group) for eight weeks, with systolic blood pressure (SBP), serum creatinine, urea, 24-hour urinary protein/sodium, renal interlobar artery blood flow, and pathological examination measured. We also examined endothelial-(CD31) and fibrosis-related protein(α-SMA) expressions in glomeruli. RESULTS: High-salt diet increased SBP (DSH vs. DSN, 205.2â ±â 8.9 vs. 135.4â ±â 7.9 mm Hg, Pâ <â 0.01), 24-hour urinary protein (132.55â ±â 11.75 vs. 23.52â ±â 5.94 mg/day, Pâ <â 0.05), urine sodium excretions (14.09â ±â 1.49 vs. 0.47â ±â 0.06 mmol/day, Pâ <â 0.05), and renal interlobar artery resistance. Glomerulosclerosis increased (26.1â ±â 4.6 vs. 7.3â ±â 1.6%, Pâ <â 0.05), glomerular CD31 expressions decreased while α-SMA expression increased in DSH group. Immunofluorescence staining showed that CD31 and α-SMA co-expressed in glomeruli of the DSH group. The degree of glomerulosclerosis negatively correlated with CD31 expressions (râ =â -0.823, Pâ <â 0.01) but positively correlated with α-SMA expressions (râ =â 0.936, Pâ <â 0.01). CONCLUSIONS: We demonstrated that a high-salt diet led to glomerulosclerosis involving the EndMT process, which played an essential role in glomerulosclerosis in hypertensive Dahl-SS rats.
Subject(s)
Diabetes Mellitus, Experimental , Hypertension, Renal , Hypertension , Male , Rats , Animals , Rats, Inbred Dahl , Sodium Chloride , Diabetes Mellitus, Experimental/metabolism , Kidney/metabolism , Hypertension/metabolism , Blood Pressure , Hypertension, Renal/metabolism , Sodium Chloride, Dietary/metabolism , Sodium/metabolism , Diet , FibrosisABSTRACT
The Internet and 5G era makes e-learning a vital part of modern education, and extensive evidence has shown that peer teaching and flipped classroom contribute to increased success in medical teaching. However, the applicability of these pedagogies in laboratory courses remains largely unexplored. This study aimed to evaluate the academic performance, proficiency in procedural skills, and perception of nursing students in physiology laboratory classes delivered with nontraditional classroom (NTC) pedagogies comprising the combination of e-learning, peer teaching, and flipped classroom. Each class was subdivided into two equal halves by successive student identification (ID) number and randomly assigned to the control or NTC group. Compared to the control class, NTC teaching significantly enhanced mean score of six preclass tests (67.77 ± 9.83 vs. 62.94 ± 9.70), with "B" graders increased obviously, suggesting that preclass e-learning was more effective than textbook-based preview, especially for general grasp of the topic. Similarly, average scores on postclass quizzes in the NTC group were improved (79.40 ± 9.12 vs. 74.43 ± 8.88). Lesser time cost and higher success rates were observed in trachea, artery, and heart catheterizations in the NTC group, although no disparities were found in ureteral intubation. The majority (â¼74%) of students supported the reform and shared positive experiences with NTC methodology. They reported that virtual experiments and self-paced procedural skill videos affected pre- and in-class learning outcomes most, respectively. These findings indicated that NTC pedagogy was workable to improve students' subject scores and proficiency in complicated and direct-viewing procedural skills and was favorable to students.
Subject(s)
Computer-Assisted Instruction , Students, Nursing , Curriculum , Humans , Laboratories , Problem-Based Learning , TeachingABSTRACT
The motion intent recognition via lower limb prosthesis can be regarded as a kind of short-term action recognition, where the major issue is to explore the gait instantaneous conversion (known as transitional pattern) between each two adjacent different steady states of gait mode. Traditional intent recognition methods usually employ a set of statistical features to classify the transitional patterns. However, the statistical features of the short-term signals via the instantaneous conversion are empirically unstable, which may degrade the classification accuracy. Bearing this in mind, we introduce the one-dimensional dual-tree complex wavelet transform (1D-DTCWT) to address the motion intent recognition via lower limb prosthesis. On the one hand, the local analysis ability of the wavelet transform can amplify the instantaneous variation characteristics of gait information, making the extracted features of instantaneous pattern between two adjacent different steady states more stable. On the other hand, the translation invariance and direction selectivity of 1D-DTCWT can help to explore the continuous features of patterns, which better reflects the inherent continuity of human lower limb movements. In the experiments, we have recruited ten able-bodied subjects and one amputee subject and collected data by performing five steady states and eight transitional states. The experimental results show that the recognition accuracy of the able-bodied subjects has reached 98.91%, 98.92%, and 97.27% for the steady states, transitional states, and total motion states, respectively. Furthermore, the accuracy of the amputee has reached 100%, 91.16%, and 90.27% for the steady states, transitional states, and total motion states, respectively. The above evidence finally indicates that the proposed method can better explore the gait instantaneous conversion (better expressed as motion intent) between each two adjacent different steady states compared with the state-of-the-art.
Subject(s)
Amputees , Artificial Limbs , Algorithms , Humans , Motion , Wavelet AnalysisABSTRACT
Platinum-based drugs are the mainstay of chemotherapy regimens in a clinic, but their use is seriously limited by severe side effects and drug resistance. A cetuximab-decorated drug delivery system can selectively deliver drugs into EGFR-highexpressing cancer cells to prevent the shortcomings of platinum-based chemotherapy. Here, cetuximab-decorated and near-infrared (NIR)-activated nanoparticles based on Pt(IV)-prodrug (abbreviated as Cetuximab-Pt-INPs) was constructed. First, PEGylated Pt(IV)-prodrug was synthesized by a condensation reaction between c,c,t-[Pt(NH3)2Cl2(OOCCH2CH2COOH)(OH)] and MPEG-PLA. Then, Pt(IV)-prodrug and indocyanine green co-encapsulated nanoparticles (Pt-INPs) were prepared through an ultrasonic emulsification method. Finally, Cetuximab-Pt-INPs were obtained by decorating Pt-INPs with cetuximab as a targeting vector. The optimized Cetuximab-Pt-INPs exhibited a spherical core-shell shape of 138.5 ± 0.96 nm. In-vitro cellular uptake and cytotoxicity assays revealed that more Cetuximab-Pt-INPs with NIR irradiation were selectively taken up by A431 cells, thereby leading to higher cytotoxicity. These multifunctional nanoparticles may have promising potential for targeted and effective therapy against EGFR-highexpressing cells of epidermoid carcinoma.
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BACKGROUND: Hyaluronan (HA) metabolism by chondrocytes is important for cartilage development and homeostasis. However, information about the function of circular RNAs (circRNAs) in HA metabolism is limited. We therefore profiled the role of the novel HA-related circRNA circHYBID in the progression of osteoarthritis (OA). METHODS: CircHYBID function in HA metabolism in chondrocytes was investigated using gain-of-function experiments, and circHYBID mechanism was confirmed via bioinformatics analysis and luciferase assays. The expression of circHYBID-hsa-miR-29b-3p-transforming growth factor (TGF)-ß1 axis was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. CircHYBID, TGF-ß1, and HA levels in cartilage samples were evaluated using qRT-PCR and pathological examination. Enzyme-linked immunosorbent assay was used to assess HA accumulation in chondrocyte supernatant. RESULTS: CircHYBID expression was significantly downregulated in damaged cartilage samples compared with that in the corresponding intact cartilage samples. CircHYBID expression was positively correlated with alcian blue score. Interleukin-1ß stimulation in chondrocytes downregulated circHYBID expression and decreased HA accumulation. Gain-of-function experiments revealed that circHYBID overexpression in chondrocytes increased HA accumulation by regulating HA synthase 2 and HYBID expression. Further mechanism analysis showed that circHYBID upregulated TGF-ß1 expression by sponging hsa-miR-29b-3p. CONCLUSIONS: Our results describe a novel HA-related circRNA that could promote HA synthesis and accumulation. The circHYBID-hsa-miR-29b-3p-TGF-ß1 axis may play a powerful regulatory role in HA metabolism and OA progression. Thus, these findings will provide new perspectives for studies on OA pathogenesis, and circHYBID may serve as a potential target for OA therapy.
Subject(s)
Chondrocytes/metabolism , Gene Expression Regulation , Hyaluronic Acid/metabolism , RNA Interference , RNA, Circular/genetics , Transforming Growth Factor beta1/genetics , Biomarkers , Cells, Cultured , Disease Susceptibility , Extracellular Matrix/metabolism , Gene Expression Profiling , Gene Regulatory Networks , Humans , Immunohistochemistry , MicroRNAs/genetics , Osteoarthritis/etiology , Osteoarthritis/metabolism , Osteoarthritis/pathology , Proteoglycans/metabolism , Transforming Growth Factor beta1/metabolismABSTRACT
BACKGROUND: Many methods have been proposed to increase cup coverage by host bone during primary total hip arthroplasty (THA) in hip osteoarthritis secondary to developmental dysplasia of the hip (DDH). However, there was no study comparing the results of controlled fracture of the medial wall with a structural autograft with a bulk femoral head. METHODS: Sixty-seven hips classified as Crowe II/III were retrospectively included in this cohort study, which consisted of 33 controlled fractures (group A) and 34 structural autografts (group B). The Harris Hip Scores (HHS) were recorded. The radiological assessments were analyzed. Also, complications are assessed. The paired-sample t test was used for data analysis before and after the operation, while the independent sample T test was used for the comparison between the two groups. The Pearson chi-square test or the Fisher exact test was used to analyze the qualitative comparative parameters. Kaplan-Meier was utilized in the analysis of survivorship with the end points as a revision for any component. RESULTS: All patients were reconstructed acetabulum at the anatomical location. HHS increased greatly for both groups (p = 0.18). No statistic difference was observed for the two groups in postoperative leg-length discrepancy (0.51 ± 0.29 cm for group A and 0.46 ± 0.39 cm for group B, p = 0.64 ), postoperative height of the hip center (2.25 ± 0.42 cm for group A and 2.09 ± 0.31 cm for group B, p = 0.13), and inclination of the cup (39 ± 4° for group A and 38 ± 3° for group B, p = 0.65 ). The rate of cup coverage for group B (94 ± 2%) was better than for group A (91 ± 5%), (p = .009). The rate of cup protrusio was 48 ± 4% for group A. For both groups, no statistical difference was observed in the cup diameter (p > .05), while group A showed less operation time than group B (p < .001). No complications were observed at the latest follow-up. CONCLUSION: Controlled fracture of the medial wall to increase cup coverage by host bone at the anatomical location can act as an alternative technique for DDH Crowe II/III with the advantage of shorter operation time and less technically demanding.
Subject(s)
Acetabulum/surgery , Arthroplasty, Replacement, Hip/methods , Autografts , Developmental Dysplasia of the Hip/complications , Femur Head/surgery , Hip Prosthesis , Osteoarthritis, Hip/etiology , Osteoarthritis, Hip/surgery , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Operative Time , Postoperative Complications/prevention & control , Retrospective StudiesABSTRACT
The objective of this study was to investigate the effect of dispersion states of azone in gels on the transdermal permeation of levamisole hydrochloride (LH). LH hydroalcoholic gels containing azone of different dispersion states were prepared by varying the contents of azone and Tween 80, and the in vitro transdermal permeation of LH across excised rat skin was evaluated. Depending on the content of azone, mixed solvents, and solubilizer used, azone presented as dissolved molecules, solubilized in micelles, and fine or coarse emulsion droplets in gels. Dramatically increased transdermal permeation of LH within the azone contents between 0.25% and 0.75% indicated high transdermal enhancement efficiency of the molecular or micellar azone, and extra azone that existed as oil droplets did not fully exert transdermal penetration enhancement of LH. Although solubilizer (Tween 80) can greatly increase the solubility of azone, only small amount of Tween 80 (0.5%) in the gel significantly increased the steady-state flux of LH. Addition of extra amount of Tween 80 (>0.5%) reduced the amount of azone distributed in the skin, and thus decreased the transdermal drug permeation. The results partly elucidated the versatile effects of the dispersion states of azone on the transdermal permeation of hydrophilic drug from semisolid gels.
Subject(s)
Antinematodal Agents/pharmacokinetics , Antirheumatic Agents/pharmacokinetics , Azepines/chemistry , Hydrogels/chemistry , Levamisole/pharmacokinetics , Skin Absorption/drug effects , Administration, Cutaneous , Animals , Antinematodal Agents/administration & dosage , Antirheumatic Agents/administration & dosage , Azepines/pharmacology , Hydrogels/pharmacology , Levamisole/administration & dosage , Male , Micelles , Permeability/drug effects , Rats, Sprague-Dawley , Skin/drug effects , Skin/metabolism , SolubilityABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of metronomic chemotherapy of low dose phosphoramide combined with prednisolone (CP metronomic chemotherapy) on proliferation and apoptosis of RPMI 8226 cells, and to explore its regulating effect on Notch1/NF-κB signaling pathways.</p><p><b>METHODS</b>Experiment was divided into the DMSO control group, and the phosphoramide mustard (PM) group, the prednisolone group, the phosphoramide mustard plus prednisolone group (the CP group). RPMI 8226 cells were treated with different drugs, CCK-8 method was used to detect cell proliferation, flow cytometry was used to detect the cell cycle and apoptosis, reverse transcription PCR was used to detect Notch1 and NF-κB mRNA expression level.</p><p><b>RESULTS</b>Compared with DMSO control group, RPMI8226 cell proliferation inhibition rate in all the PM, prednisolone and CP groups increased significantly with prolonging of time (r of 0.994,0.996,0.999, respectively, P<0.001). And at the same time, the inhibitory rate of cell proliferation was significantly different; the cell inhibitory rate in PM group was lowest, that in CP group was highgest, that in prednissone group was intermediate (P<0.01). After 48 hours, compared with the DMSO control group, the G/Gcell proportion in treatment group increased significantly, S phase cell proportion decreased significantly, especially in PM and CP groups. The G/M phase cell proportion increased in PM group, while reduced in the prednisolone and the CP groups. After 48 hours, compared with the DMSO control group, RPMI 8226 cell apoptosis rate increased as follow: in PM, pre-dnisolone and CP group(P<0.01). After 48 hours, compared with the DMSO control group, Notch1 and NF-κB mRNA expression in the prednisolone, the PM and the CP group decreased significantly(P<0.001).</p><p><b>CONCLUSION</b>CP metronomic chemotherapy can significantly reduce RPMI 8226 cell proliferation, promote RPMI 8226 cell apoptosis, arrest RPMI 8226 cells mainly in the G/Gphase, and significantly reduce Notch1 and NF-κB expression levels. It is suggested that Notch1/NF-κB signaling pathways is involved in CP metronomic chemotherapy for MM.</p>
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Air temperature is the input variable of numerous models in agriculture, hydrology, climate, and ecology. Currently, in study areas where the terrain is complex, methods taking into account correlation between temperature and environment variables and autocorrelation of regression residual (e.g., regression Kriging, RK) are mainly adopted to interpolate the temperature. However, such methods are based on the global ordinary least squares (OLS) regression technique, without taking into account the spatial nonstationary relationship of environment variables. Geographically weighted regression-Kriging (GWRK) is a kind of method that takes into account spatial nonstationarity relationship of environment variables and spatial autocorrelation of regression residuals of environment variables. In this study, according to the results of correlation and stepwise regression analysis, RK1 (covariates only included altitude), GWRK1 (covariates only included altitude), RK2 (covariates included latitude, altitude and closest distance to the seaside) and GWRK2 (co-variates included altitude and closest distance to the seaside) were compared to predict the spatial distribution of mean daily air temperature on Hainan Island on December 18, 2013. The prediction accuracy was assessed using the maximum positive error, maximum negative error, mean absolute error and root mean squared error based on the 80 validation sites. The results showed that GWRK1's four assessment indices were all closest to 0. The fact that RK2 and GWRK2 were worse than RK1 and GWRK1 implied that correlation among covariates reduced model performance.
Subject(s)
Climate , Spatial Analysis , Temperature , China , Islands , Models, Theoretical , Spatial RegressionABSTRACT
Understanding daily minimum temperature is of great importance for assessing low temperature damages to crops and guiding people to take timely remedial measures to ensure food security. Kriging is a widely used technology for mapping the spatial distribution of the near-surface temperature. However, the smoothing effect, commonly found in the Kriging maps, leads to low values to be overestimated and high values to he underestimated. For daily minimum temperature on Hainan Island which was affected by cold air on December 12, 2011, cross-validation was adopted to evaluate the prediction accuracy of ordinary Kriging (OK) and Kriging with external drift (KED). The spatial distribution maps of daily minimum temperature on Hainan Island on December 12, 2011 produced by OK and sequential Gaussian simulation (SGS) were compared. Results showed that the prediction accuracy of KED (r = 0.86) was not superior to OK (r = 0.86) significantly. SGS could generate multiple equiprobable simulation realizations, and the distribution and variance function of the original data could be reproduced in the realizations. The simulation realizations generated by SGS overcame the smoothing effect of Kriging and could more truly reflect the spatial distribution of minimum temperature on the day on Hainan Island. In the region where daily minimum temperature was low, and the temperature change was small, the conditional variance of the SGS results was less than the ordinary Kriging variance. Spatial uncertainty of a potential chilling damage area could be quantified by multiple simulation realizations generated by SGS. SGS was a valuable tool for assessing agro-meteorological disasters caused by low temperature.
Subject(s)
Spatial Analysis , Temperature , China , Islands , UncertaintyABSTRACT
<p><b>OBJECTIVE</b>To investigate effects of low-dose cyclophosphamide and prednisone (CP) metronomic chemotherapy on microvessel density of bone marrow, serum vascular endothelial growth factor (VEGF) and platelet derived growth factor BB (PDGF-BB)in multiple myeloma (MM) patients.</p><p><b>METHODS</b>54 refractory or relapsed MM patients were treated with CP metronomic chemotherapy consisted of oral cyclophosphamide (CTX, 50 mg/d) and prednisone (Pred, 15 mg/d). Bone marrow and peripheral blood of each patient were collected before and 2, 4, 6 months after treatment. Among the 37 assessable patients, 30 cases were responsive with the response rate of 81.08%. Another 17 cases were follow-uped less than 6 months or failure to obtain serum samples or lost to follow-up. Microvessel density of bone marrow was measured by immunohistochemistry and serum VEGF/PDGF-BB expression was analyzed by ELISA in the 37 assessable patients.</p><p><b>RESULTS</b>2, 4, 6 months following CP metronomic chemotherapy, microvessel densities of bone marrow in the responders were 33.1 ± 4.8/HP, 24.8 ± 3.7/HP, 19.7 ± 2.1/HP respectively; the expressions of VEGF were (394 ± 57) ng/L, (268 ± 32) ng/L and (217 ± 20) ng/L respectively; the expressions of PDGF-BB were (304 ± 31) ng/L, (274 ± 31) ng/L and (196 ± 22) ng/L respectively. After CP metronomic chemotherapy, there were significantly lower of microvessel density, VEGF and PDGF-BB levels than pretreatment \[MVD 48.5 ± 5.9/HP, VEGF (517 ± 60) ng/L, PDGF-BB (484 ± 60) ng/L\]in the responders (P < 0.01). While in the non-responders, after treated by CP metronomic chemotherapy for 2 months, microvessel density, the expression of VEGF and the expression of PDGF-BB were 32.5 ± 4.7/HP, 512 ± 39 ng/L and (452 ± 39) ng/L respectively. There were no significant changes of MVD, VEGF and PDGF-BB levels compared with pretreatment \[MVD 33.2 ± 5.6/HP,VEGF (498 ± 55) ng/L, PDGF-BB (488 ± 44) ng/L\] (P > 0.05).</p><p><b>CONCLUSIONS</b>Our findings suggested that continuous low-dose CP metronomic chemotherapy could decrease microvessel density of bone marrow in MM patients. Furthermore, it down-regulated expression of serum VEGF and PDGF-BB to exert its anti-angiogenesis in MM.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Angiogenesis Inhibitors , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Cyclophosphamide , Microvessels , Multiple Myeloma , Blood , Drug Therapy , Prednisone , Proto-Oncogene Proteins c-sis , Blood , Vascular Endothelial Growth Factor A , BloodABSTRACT
A field experiment was conducted in a winter wheat field in Weibei dry highland region of Loess Plateau to study the effects of different mulching and fertilization treatments on soil moisture regime. The treatments were 1) no fertilization, 2) conventional fertilization, 3) recommended fertilization, 4) recommended fertilization + manure, 5) recommended fertilization + plastic mulch on soil ridges, 6) recommended fertilization + plastic mulch on soil ridges and straw mulch in furrows, and 7) recommended fertilization + straw mulch on entire plot. Soil moisture content was determined regularly with a neutron probe. Among the treatments, recommended fertilization plus plastic mulch on soil ridges and straw mulch in furrows in dry season (spring) resulted in the greatest increase of soil water storage and maintained the storage to the critical stage crops needed, followed by recommended fertilization plus plastic mulch on soil ridges. These two treatments could store more precipitation in field, and would benefit the development of rainfed agriculture in dry highland region of Loess Plateau. As for recommended fertilization plus manure, it had the least increase of soil water storage, with a difference of 48.2 mm to the recommended fertilization plus plastic mulch on soil ridges and straw mulch in furrows in dry season.
Subject(s)
Agriculture/methods , Fertilizers , Soil/analysis , Triticum/growth & development , Water/analysis , Altitude , ChinaABSTRACT
Genistein (4',5,7-trihydroxyisoflavone) is the most abundant isoflavone found in the soybean that exhibits an anti-inflammatory effect. The present study was designed to examine the effects of genistein on expression levels of hemolysate-induced proinflammatory and adhesion molecules in SD rat brain microvascular endothelial cells (BMECs). Genistein treatment attenuated hemolysate-induced nuclear factor-kappa B (NF-kappaB) p65 translocation in BMECs. In addition, genistein suppressed the expression levels of tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein 1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1), but not vascular cell adhesion molecule-1 (VCAM-1). The inhibitory rate of 50 pM genistein for TNF-alpha, MCP-1 and ICAM-1 was 65.4%, 60.5% and 54.9% respectively. These inhibitory effects of genistein on proinflammatory and adhesion molecules were not due to decreased BMEC viability as assessed by MTT test. Taken together the present study suggests that genistein suppresses expression levels of hemolysate-induced pro-inflammatory and adhesion molecules in cerebral endothelial cells.
Subject(s)
Cell Adhesion Molecules/metabolism , Cell Extracts/pharmacology , Cytokines/metabolism , Endothelial Cells/drug effects , Endothelium, Vascular/cytology , Genistein/pharmacology , Phytoestrogens/pharmacology , Animals , Animals, Newborn , Brain/anatomy & histology , Cell Adhesion Molecules/classification , Cell Adhesion Molecules/genetics , Cell Survival/drug effects , Cells, Cultured , Cytokines/classification , Cytokines/genetics , Dose-Response Relationship, Drug , Gene Expression Regulation/drug effects , NF-kappa B/genetics , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that plays an important role in the recruitment of macrophages. Although previous studies have demonstrated that MCP-1 has been shown to be involved in the damaging inflammatory processes associated with stroke, infection, neoplasia, and others in the central nervous system, the role of MCP-1 in the cerebral artery after experimental subarachnoid hemorrhage (SAH) in rats has been largely unexplored. This study was undertaken to investigate the expression of the MCP-1 in SAH model and to clarify the potential role of MCP-1 in cerebral vasospasm. A total of 80 rats were randomly divided into four groups: control group; day 3, day 5, and day 7 groups. Day 3, day 5, and day 7 groups were all SAH groups. The animals in day 3, day 5 and day 7 groups were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2 and were killed on days 3, 5, and 7, respectively. Cross-sectional area of basilar artery was measured and the MCP-1 expression was assessed by real-time PCR, Western blot and immunohistochemistry. The cross-sectional area of basilar artery was found to be 85,373+/-8794 mum(2) in control group, 59,210+/-7281 mum(2) in day 3, 50,536+/-6519 mum(2) in day 5, and 66,360+/-7452 mum(2) in day 7, respectively. The basilar arteries exhibited vasospasm after SAH and became more severe on day 5. The elevated mRNA and protein of MCP-1 were detected after SAH and peaked on day 5. MCP-1 is increasingly expressed in a parallel time course to the development of cerebral vasospasm in a rat experimental model of SAH and these findings might have important implications during the administration of specific MCP-1 antagonists in order to prevent or reduce cerebral vasospasm caused by SAH.
Subject(s)
Basilar Artery/physiology , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Animals , Cerebrovascular Circulation/physiology , Disease Models, Animal , Immunohistochemistry , Male , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Subarachnoid Hemorrhage/immunology , Subarachnoid Hemorrhage/metabolism , Subarachnoid Hemorrhage/physiopathology , Vasospasm, Intracranial/immunology , Vasospasm, Intracranial/metabolism , Vasospasm, Intracranial/physiopathologyABSTRACT
Genistein is a major isoflavone compound from soybean. We investigated the anti-inflammatory properties of genistein in primary astrocytes treated with hemolysate. The results indicated that genistein inhibited the expression of hemolysate induced iNOS and COX-2 mRNA on astrocytes. Furthermore, this compound inhibited the level of hemolysate-stimulated nuclear factor-kappa B (NF-small ka, CyrillicB). Therefore, we suggested that the effect of genistein-mediated inhibition of the expression hemolysate-induced iNOS and COX-2 genes is due to under the suppression of NF-small ka, CyrillicB activation in the transcriptional level.
Subject(s)
Astrocytes/drug effects , Cyclooxygenase 2/metabolism , Genistein/pharmacology , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Astrocytes/metabolism , Blotting, Western , Cell Survival/drug effects , Cells, Cultured , Cyclooxygenase 2/genetics , Nitric Oxide Synthase Type II/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVES: The purpose of this study was to evaluate the movement of pure titanium implants under different continuous forces in the edentulous alveolar ridge. MATERIAL AND METHODS: Four pairs of titanium implants were inserted into the right maxillary and mandibular post-extraction edentulous ridge of the experimental dog. Three different levels of continuous force (100, 200, and 500 g) were loaded onto three pairs of adjacent implant abutments using a memory Ni-Ti coil spring for up to 6 months and the remaining two implant abutments as the control group received no force. The positions of implant abutments were observed and the distances between the implants abutment at the top, middle and base levels were measured at the 0th, 2nd, 3rd, 6th and 8th month of the follow-up period. RESULTS: There was no significant change in the distances between adjacent abutments loaded with 100 or 200 g continuous forces throughout the entire study period. However, significantly more movement of implant abutments was noted in the 500 g pair after the 3rd month of loading when compared with the 200 or the 100 g pair (both P < 0.001). This change further increased at the 6th month (P < 0.001, 0.01, respectively). Moreover, the difference in the measurements at the top, middle and base level indicated that the two adjacent implants moved in a tipping manner in the 500 g pair after 3 and 6 months of loading. CONCLUSION: The osseointegrated implants remained stable and rigid with a pulling force of 100 and 200 g after 6 months of loading. However, when the force reached 500 g, the implants moved in an inward-tipping pattern. The results suggested that endosseous titanium implants might not necessarily be rigid anchorages under all circumstances.