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1.
BMC Musculoskelet Disord ; 24(1): 89, 2023 Feb 02.
Article in English | MEDLINE | ID: mdl-36732725

ABSTRACT

BACKGROUND: Short-stem hip arthroplasty (SHA) is characterized by metaphyseal load transfer that effectively preserves the bone stock, but still suffers from stress shielding in the proximal femur. We designed a tension screw to mimic tension trabeculae in the new bionic collum femoris preserving (BCFP) short stem for bionic reconstruction, aiming to restore the biomechanics of hip joint. METHODS: Native femur finite element model was constructed to investigate the biomechanics of hip joint based on computed tomography (CT) data. The maximum absolute principal stress/strain cloud chart allowed the direction of stress/strain to be assessed. Six BCFP models with different screw angles (5°, 10°, 15°, 20°, 25°, and 30°) and the Corail model were created. The stress/strain distribution and overall stiffness were compared between each of the BCFP and Corail implanted models. RESULTS: The native model visualized the transfer pathways of tensile and compressive stress. The BCFP stems showed significantly higher stress and strain distribution in the greater trochanteric region compared to conventional total hip arthroplasty (THA). In particular, the BCFP-5° stem demonstrated the highest average strain in both medial and lateral regions and the overall stiffness was closest to the intact femur. CONCLUSIONS: Stress transfer pathways of trabecular architecture provide biomechanical insight that serves as the basis for bionic reconstruction. The tension screw improves load transfer pattern in the proximal femur and prevents stress reduction in the greater trochanteric region. The BCFP-5° stem minimizes the stress shielding effect and presents a more bionic mechanical performance.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Humans , Arthroplasty, Replacement, Hip/methods , Finite Element Analysis , Bionics , Femur/diagnostic imaging , Femur/surgery , Biomechanical Phenomena , Stress, Mechanical , Prosthesis Design
2.
J Biomech Eng ; 144(4)2022 04 01.
Article in English | MEDLINE | ID: mdl-34729598

ABSTRACT

Stress shielding is an important factor in the internal fixation of a fracture. To explore the regularity of stress shielding in internal fixation, a simplified model of a comminuted femoral shaft fracture bridged by a locking plate was established and finite element analysis was performed to analyze the load distribution between the plate and femur from the proximal end of the femur to the fracture line and investigate the stress shielding degree of the plate on the bone. The stress, deformation, and axial compressive force distribution of four internal fixation schemes under compression were obtained, and the stress shielding degrees on each section was calculated. To compare the regularity of stress shielding and flow distribution, the relationship between the compressive force increment and stress shielding degree was established. The normalized curves of compressive force increment with the plate section position were compared with the flow distribution in a Z-type manifold, a parallel pipe system similar to an internal fixation system in structure and working characteristics. For quantitative comparison, the similarity between normalized curves of the compressive force increment and simulated flow distribution was calculated. The regularity of load distribution along the section position of the plate was similar to the flow distribution in the Z-type manifold. Therefore, the flow distribution pattern of the Z-type manifold can be used to characterize the regularity of load distribution in internal fixation. This study provided a new method to characterize the stress shielding degree of a locking plate on bone.


Subject(s)
Femoral Fractures , Fracture Fixation, Internal , Biomechanical Phenomena , Bone Plates , Femoral Fractures/surgery , Finite Element Analysis , Fracture Fixation, Internal/methods , Humans
3.
BMC Musculoskelet Disord ; 23(1): 592, 2022 Jun 20.
Article in English | MEDLINE | ID: mdl-35725436

ABSTRACT

PURPOSE: We built a joint replacement loosening model based on the original rabbit model of infection and evaluated the performance characteristics of 18F-FDG and 68 Ga-FAPI in evaluating infection and loosening. METHODS: After surgery, the rabbits were divided into four groups, with six individuals in the control group and 10 each in the aseptic loosening, S. aureus and S. epidermidis groups. PET/CT and serological examination were performed three times at two-week intervals. After the rabbits were euthanized, micro-CT, tissue pathology, pullout tests and scanning electron microscopy (SEM) were performed. RESULTS: The pullout test and SEM showed the feasibility of the aseptic loosening model. 18F-FDG showed similar performance in the control and loosening groups. The SUVmax of the S. aureus group was consistently higher than that of the S. epidermidis group. As for 68 Ga-FAPI, the SUVmax of the control group was lowest in the second week and gradually increased over subsequent weeks. The SUVmax of the loosening group began to exceed that of the control group after the second week. The SUVmax of the S. aureus group in the second week was the lowest among the four groups and increased as the number of weeks increased. The pathology results showed concordance with the performance of PET/CT. Linear regressions between SUVmax and serology showed that 18F-FDG was positively correlated with CRP and IL-6, while 68 Ga-FAPI revealed negative correlations with CRP and IL-6 in the second week and positive correlations in the sixth week. In addition, the SUVmax and MT(target)V of both 18F-FDG and 68 Ga-FAPI were negatively correlated with bone volume/trabecular volume (TV) and bone surface area/TV. CONCLUSION: In this longitudinal observation, 68 Ga-FAPI showed greater sensitivity than 18F-FDG in detecting diseases, and 68 Ga-FAPI had no intestinal or muscular uptake. The MT(target)V of 68 Ga-FAPI was larger than that of 18F-FDG, which meant that 68 Ga-FAPI had the potential to define the scope of lesions more accurately. Finally, the SUVmax of 68 Ga-FAPI could not differentiate between loosening and infection; further study of the diagnostic criteria is warranted.


Subject(s)
Arthritis, Infectious , Prosthesis-Related Infections , Animals , Fluorodeoxyglucose F18 , Interleukin-6 , Positron Emission Tomography Computed Tomography/methods , Prosthesis-Related Infections/diagnostic imaging , Prosthesis-Related Infections/etiology , Rabbits , Staphylococcus aureus
4.
Exp Parasitol ; 198: 87-94, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30763571

ABSTRACT

Phage display technology to produce recombinant monoclonal antibodies or antibody fragments permits the identification of sought after antibodies in short time frames at low cost along with direct and rapid selection for antibody characteristics. Monoclonal antibodies can facilitate the identification and characterisation of parasite molecules that function at the host-parasite interface to help understand at the molecular level the biology of the parasite and disease progression, which often leads to new drug targets, diagnostic antigens or vaccine candidates. The trematode Fasciola hepatica is an important veterinary and human parasite. In this work, we infected rats with F. hepatica and amplified the generated antibody repertoire to produce a single-chain variable fragment (scFv) phage display library. The library was used to identify a scFv that recognises cathepsin L1, a major component of the adult parasites excretory/secretory material and an important vaccine candidate. This is the first report of the construction of a phage display antibody library from a F. hepatica infected host, and also the first instance such a library has been used to identify an affinity-matured monoclonal antibody fragment that binds to a F. hepatica antigen. The scFv library and methods detailed should facilitate future research characterising F. hepatica antigens.


Subject(s)
Antibodies, Helminth/immunology , Cathepsins/immunology , Fasciola hepatica/immunology , Peptide Library , Amino Acid Sequence , Animals , Antibodies, Monoclonal/immunology , Antigens, Helminth/immunology , Cell Surface Display Techniques , Cloning, Molecular , Electrophoresis, Agar Gel , Gene Library , Immunoblotting , Immunoglobulin Variable Region/chemistry , Polymerase Chain Reaction , Rats , Rats, Inbred Lew , Single-Chain Antibodies/genetics , Single-Chain Antibodies/immunology
5.
Nano Lett ; 18(5): 2976-2983, 2018 05 09.
Article in English | MEDLINE | ID: mdl-29714487

ABSTRACT

Freestanding nanomaterials (such as nanowires, nanoribbons, and nanotubes) are known to exhibit ultralarge elastic strains and ultrahigh strengths. However, harnessing their superior intrinsic mechanical properties in bulk composites has proven to be difficult. A recent breakthrough has overcome this difficulty by using a martensitic phase transforming matrix in which ultralarge elastic strains approaching the theoretical limit is achieved in Nb nanowires embedded in the matrix. This discovery, breaking a long-standing challenge, still limits our ability of harnessing the exceptional properties of nanomaterials and developing ultrahigh strength bulk materials to a narrow selection of phase transforming alloy matrices. In this study, we investigated the possibility to harness the intrinsic mechanical properties of nanoinclusions in conventional dislocation slip matrix based on a principle of synergy between the inclusion and the matrix. The small spacing between the densely populated hard and dislocation-impenetrable nanoinclusions departmentalize the plastic matrix into small domains to effectively impede dislocation motion within the matrix, inducing significant strengthening and large local elastic strains of the matrix, which in turn induced large elastic strains in the nanoinclusions. This dual phase synergy is verified in a Ti3Sn inclusions/B2-NiTi(Fe) plastic matrix model materials system. The maximum elastic strain of Ti3Sn inclusion obtained in the dislocation slip matrix is comparable to that achieved in a phase transforming matrix. This finding opens new opportunities for the development of high-strength nanocomposites.

6.
Int Orthop ; 43(5): 1277, 2019 May.
Article in English | MEDLINE | ID: mdl-30707254

ABSTRACT

In the original publication, the following authors have been omitted due to a technical error in the original article.

7.
Tumour Biol ; 35(9): 8659-64, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24867098

ABSTRACT

The tyrosine and phosphoinositide kinases play crucial roles in the regulation of many cancer cell processes including cell survival and cell motility. Anaplastic thyroid carcinoma (ATC) is a rare and deadly type of thyroid cancer, and so far, there are no effective therapeutic compounds for ATC. Herein, we investigate the anticancer activities of PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, in ATC therapy. We found that PP121 is effective at suppressing cell viability, inducing cell apoptosis, and inhibiting cell migration and invasion. The potential anticancer mechanism for PP121 might be its inhibitory effects on phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in ATC cells. Furthermore, PP121 is effective at suppressing ATC tumor growth in vivo. In summary, our studies suggest that PP121 might be a promising therapeutic compound for ATC treatment, which might shed new light on ATC therapy.


Subject(s)
Cell Movement/drug effects , Cell Proliferation/drug effects , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Thyroid Carcinoma, Anaplastic/drug therapy , Thyroid Neoplasms/drug therapy , 1-Phosphatidylinositol 4-Kinase/antagonists & inhibitors , 1-Phosphatidylinositol 4-Kinase/metabolism , Animals , Apoptosis/drug effects , Blotting, Western , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Immunohistochemistry , Mice, Nude , Microscopy, Fluorescence , Phosphatidylinositol 3-Kinases/metabolism , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Thyroid Carcinoma, Anaplastic/metabolism , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Time Factors , Tumor Burden/drug effects , Xenograft Model Antitumor Assays
8.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(3): 795-800, 2014 Mar.
Article in Zh | MEDLINE | ID: mdl-25208415

ABSTRACT

Through carrying out spectral test experiment, the influence factors of spectrum test were analyzed, the influence degree of various factors in spectral recognition was explicated and the method of spectra test was optimized for cotton leaf infected by verticillium wilt. The results indicated that under different severity levels, the shape and value of reflectance of disease symptoms part were Significantly higher than healthy part on cotton leaf, compared with the black board as baseboard, the spectral values of disease leaves were slightly higher in visible light wavebands and significantly higher in others wavebands than healthy leaves on white baseboard. Different position of leaf on cotton plant has different effect degree to the recognition of disease, the effect of stem leaf was more obvious than that of else leaf, the identical leaf position was less influenced by disease than band. Test time and cotton varieties had less influence on recognizing disease by spectra, and the effect of the same condition was acceptable. Test site had no effect on disease recognition by spectra. The effect of each factor was different for recognizing disease leaf by spectra, and this study will provide reference for the researchers of crop disease diagnosis by spectra.


Subject(s)
Gossypium/microbiology , Plant Diseases , Plant Leaves/microbiology , Verticillium , Light , Spectrum Analysis
9.
Injury ; 54(2): 362-369, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36509562

ABSTRACT

BACKGROUND: We aimed to evaluate the biomechanical stiffness and strength of different internal fixation configurations and find suitable treatment strategies for low transcondylar fractures of the distal humerus. METHODS AND MATERIALS: Thirty 4th generation composite humeri were used to create low transcondylar fracture models that were fixed by orthogonal and parallel double plates as well as posterolateral plate and medial screw (PPMS) configurations (n=10 in each group) using an anatomical locking compression plate-screw system and fully threaded medial cortical screws. Posterior bending (maximum 50 N), axial loading (maximum 200 N) and internal rotation (maximum 10 N·m) were tested, in that order, for each specimen. Stiffness under different biomechanical settings among different configurations were compared. Another 18 sets of fracture models were created using these three configurations (n=6 in each group) and the load to failure under axial loading among different configurations was compared. RESULTS: Under posterior bending, the stiffness of parallel group was higher than orthogonal group (P<0.001), and orthogonal group was higher than PPMS group (P<0.001). Under axial loading, the stiffness of parallel group was higher than orthogonal group (P=0.001) and PPMS group (P<0.001); however, the difference between orthogonal and PPMS group was not statistically significant (P>0.05). Under internal rotation, the stiffness of parallel group was higher than orthogonal group (P=0.044), and orthogonal group was higher than PPMS group (P=0.029). In failure test under axial loading, the load to failure in the orthogonal group was lower than parallel group (P=0.009) and PPMS group (P=0.021), but the difference between parallel group and PPMS group was not statistically significant (P>0.05). All specimens in orthogonal group demonstrated "distal medial failure"; most specimens had "distal medial and trochlear failure" in the parallel group; most specimens exhibited "contact failure" in the PPMS group. CONCLUSION: For treating low transcondylar fractures, the overall stiffness and strength of the parallel configuration were superior to those of the orthogonal and PPMS configurations. Nevertheless, the PPMS configuration can provide adequate stability and stiffness comparable to double-plate configurations under axial loading. Therefore, the PPMS construct may have certain clinical value.


Subject(s)
Humeral Fractures , Humans , Humeral Fractures/surgery , Biomechanical Phenomena , Humerus/surgery , Fracture Fixation, Internal/methods , Bone Plates
10.
J Thorac Dis ; 15(11): 5961-5970, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38090315

ABSTRACT

Background: Pulmonary infarction (PI) is an uncommon complication of pulmonary embolism (PE). The risk factors of PI are still relatively unclear. Methods: This was a single-center retrospective review conducted on 500 patients with PE. After applying the inclusion and exclusion criteria, 386 patients diagnosed with PE were enrolled in our study. These patients were then categorized into the PI group (n=64) and the non-PI group (n=322). A comparison was conducted between the two groups regarding the clinical characteristics. Results: The occurrence of PI secondary to PE was 16.58%. In univariate analysis, recent trauma (21.9% vs. 9.9%, P=0.007), pleuritic chest pain (46.9% vs. 17.4%, P<0.001), hemoptysis (29.7% vs. 2.5%, P<0.001), fever (26.6% vs. 8.1%, P<0.001), lower limb edema/pain (37.5% vs. 14.0%, P<0.001), white blood cell (WBC) counts (37.5% vs. 24.5%, P=0.032), C-reactive protein (CRP) (65.6% vs. 41.3%, P<0.001), and pleural effusion (45.3% vs. 18.6%, P<0.001) were associated with an increased risk of PI. Multivariate analysis demonstrated that age [odds ratio (OR) 0.975, 95% confidence interval (CI): 0.951-0.999, P=0.045], pleuritic chest pain (OR 2.878, 95% CI: 1.424-5.814, P=0.003), hemoptysis (OR 10.592, 95% CI: 3.503-32.030, P<0.001), lower limb edema/pain (OR 2.778, 95% CI: 1.342-5.749, P=0.006) and pleural effusion (OR 3.127, 95% CI: 1.531-6.388, P=0.002) were independent factors of PI due to PE. No significant difference was recorded between the two groups in treatment and mortality. Conclusions: Young patients were found to be a higher risk of PI. Pleural effusion was found to be a factor for PI. PI should be considered when pleuritic chest pain, hemoptysis, or lower limb edema/pain are present with peripheral opacity.

11.
Inorg Chem ; 50(8): 3177-9, 2011 Apr 18.
Article in English | MEDLINE | ID: mdl-21434680

ABSTRACT

The reactions of a pair of enantiomers of macrocyclic nickel(II) complexes with racemic penicillamine generated two 3D hydrogen-bonded homochiral frameworks of {[Ni(f-(SS)-L)](2)(l-pends)(ClO(4))(2)}(n) (Λ-1) and {[Ni(f-(RR)-L)](2)(d-pends) (ClO(4))(2)}(n) (Δ-1). The frameworks possess 1D tubular pores and opposite right/left-handed helical porous surfaces (L = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane; pends(2-) = penicillaminedisulfide anion).

12.
Scand J Infect Dis ; 43(8): 632-41, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21428852

ABSTRACT

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a serious public health problem in China, and is primarily caused by either the Hantaan virus (HTNV) or Seoul virus (SEOV) strains. However, the causative hantavirus has only been definitively identified in a few HFRS cases, and detailed comparisons of patient data for the 2 strains are limited. METHODS: We conducted a 1-y prospective study in Heilongjiang Province, China. A total of 152 patients from 3 hospitals met the HFRS diagnostic criteria used in China. The diagnosis was further confirmed by specific immunoglobulin M to HTNV or SEOV. In addition, serum samples were tested for the presence of HTNV or SEOV using a reverse transcription-polymerase chain reaction (RT-PCR). Clinical manifestations and laboratory findings in patients with the 2 hantaviruses were subsequently compared. RESULTS: Eighty (61.1%) HTNV and 51 (38.9%) SEOV infections were identified. Fever and proteinuria, key to the diagnosis of HFRS, were observed in all patients. The clinical manifestations of hemorrhage and renal injury from SEOV infection were milder than those of HTNV infection. Interestingly, compared to patients with HTNV infection, patients with SEOV presented with a significantly longer febrile period, more normal white blood cell counts or even transient leukocytopenia, a higher incidence of liver injury related to disease severity, and a lower occurrence of the 5 typical phases of HFRS. The mortality was 6.3% in HTNV infections and 0% in SEOV infections. CONCLUSIONS: Clinical manifestations of SEOV infection appear to be milder and less typical than HTNV. This information may help us to improve the diagnosis of SEOV-infected patients.


Subject(s)
Hantaan virus/isolation & purification , Hemorrhagic Fever with Renal Syndrome/virology , Seoul virus/isolation & purification , Adolescent , Adult , Aged , China/epidemiology , Female , Genotype , Hantaan virus/genetics , Hemorrhagic Fever with Renal Syndrome/blood , Hemorrhagic Fever with Renal Syndrome/diagnosis , Hemorrhagic Fever with Renal Syndrome/epidemiology , Humans , Male , Middle Aged , Prospective Studies , Seoul virus/genetics , Statistics, Nonparametric
13.
Comput Methods Biomech Biomed Engin ; 24(14): 1588-1594, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33749449

ABSTRACT

For internal fixation of proximal femoral fractures, a screw is commonly placed into the femoral head; therefore, mechanical matching of the femoral head and screw is important. This article proposes an elastoplastic numerical model of the femoral head that takes nonlinear deformation and cancellous bone heterogeneity into account. Force-depth curves from finite element analysis based on the model were compared with those from macroindentation experiments. The maximum difference between the indentation depth shown by the finite element model and that found with macroindentation testing was 5.9%, which demonstrates that the model is valid.


Subject(s)
Femoral Fractures , Femur Head , Biomechanical Phenomena , Bone Screws , Finite Element Analysis , Fracture Fixation, Internal , Humans
14.
Front Plant Sci ; 12: 763525, 2021.
Article in English | MEDLINE | ID: mdl-35126408

ABSTRACT

Excessive fertilization, low nutrient utilization rate, and continuous deterioration of cotton field environment have adversely affected the sustainable development of cotton in Xinjiang province of China. To overcome these issues, we hypothesized that an appropriate combination of liquid organic fertilizer and chemical fertilizer (CF) would effectively reduce the input of CF without sacrificing the quality and yield of cotton. A 2-year field experiment explores the effects of three fertilization treatments on the growth, biomass accumulation, and yield of cotton. The three fertilization treatments, namely, no application of fertilizer (CK), the single application of CF, and the combined application of organic liquid fertilizer and CF (F0.6-F1.4), were set up in five ratios. Compared with CF treatment, the combined application of organic liquid fertilizer and CF treatments (F0.6-F1.2) speeded the growth period of cotton by 2-7 days with increased plant height, stem diameter, functional leaf width, and more number of branches, with 9.7-23.5 and 8.4-28.5% higher total plant biomass (TPB) and reproductive organs biomass (ROB), respectively. Compared with CF treatment, the rapid growth duration and maximum accumulation rate of reproductive organs were the highest in F0.8 treatment, with an average increase of 4.6 days and 20.3%. Increment in biomass accumulation contributed to an average increase of 21.8 and 18.9% in cotton boll number and yield, respectively, under F0.8 treatment. Principal component analysis shows that the total biomass, ROB, and total bolls per unit area were positively correlated with the yield, while stem diameter and vegetative organ biomass are negatively correlated with the yield. In conclusion, under film mulching with drip irrigation, organic liquid fertilizer combined with CF reduced by 20% (F0.8 treatment: N, P2O5, and K2O were 182, 104, and 76 kg hm-2, respectively) can sustain the normal growth, promote the accumulation rate of ROB, and lead to efficient cotton production.

15.
ACS Appl Mater Interfaces ; 12(22): 25075-25080, 2020 Jun 03.
Article in English | MEDLINE | ID: mdl-32420724

ABSTRACT

The optical and electrical properties of the blending organic film poly(3,4-ethylenedioxy-thiophene):poly(styrenesulfonate) (PEDOT:PSS) are strongly affected by its morphology, resulting in the performance variation in Si/organic hybrid solar cells. Here, a facile postsolvent treatment is used to tailor the vertical morphology of PEDOT:PSS by introducing a nonpolar solvent. X-ray photoelectron spectroscopy depth-profiling measurements show that the distribution of PEDOT and PSS on the surface of n-type Si can be changed by nonpolar solvent n-hexane (NHX) treatment, where more PSS aggregate at the bottom of the blend film and more PEDOT float up to the top, as compared with the reference sample. As a result, after NHX treatment, the average lifetime of the Si/organic films is increased from 152 µs for untreated samples to 248 µs for NHX-treated ones because of the better passivation effect of PSS on Si. Moreover, the transmission line model measurements indicate that the contact resistance (RC) of PEDOT:PSS film and the Ag electrode is decreased for better charge collection after NHX treatment. Eventually, the best power conversion efficiency (PCE) of 13.78% for NHX-treated planar solar cells is obtained, much higher than the PCE (with best of 12.78%) of reference devices without nonpolar solvent treatment. Our results provide a facile method to tailor the vertical morphology of the PEDOT:PSS in Si/organic hybrid solar cells.

16.
Eur J Drug Metab Pharmacokinet ; 45(1): 51-69, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31602595

ABSTRACT

BACKGROUND AND OBJECTIVES: Methyl 3,4-dihydroxybenzoate (MDHB) has the potential to prevent neurodegenerative diseases (NDDs). The present work investigated its excretion, metabolism, and cytochrome P450-based drug-drug interactions (DDIs). METHODS: After intragastric administration of MDHB, the parent drug was assayed in the urine and faeces of mice. Metabolites of MDHB in the urine, faeces, brain, plasma and liver were detected by liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). A cocktail approach was used to evaluate the inhibition of cytochrome P450 isoforms by MDHB. RESULTS: The cumulative excretion permille of MDHB in the urine and faeces were found to be 0.67 ± 0.31 and 0.49 ± 0.44‰, respectively. A total of 96 metabolites of MDHB were identified, and all IC50 (half-maximal inhibitory concentration) values of MDHB towards cytochrome P450 isoforms were > 100 µM. CONCLUSIONS: The results suggest that MDHB has a low parent drug cumulative excretion percentage and that MDHB has multiple metabolites and is mainly metabolized through the loss of -CH2 and -CO2, the loss of -CH2O, ester bond hydrolysis, the loss of -O and -CO2, isomerization, methylation, sulfate conjugation, the loss of -CH2O and -O and glycine conjugation, glycine conjugation, the loss of two -O groups and alanine conjugation, the loss of -CH2O and -O and glucose conjugation, glucuronidation, glucose conjugation, etc., in vivo. Finally, MDHB has a low probability of cytochrome P450-based DDIs.


Subject(s)
Cytochrome P-450 Enzyme System/drug effects , Hydroxybenzoates/metabolism , Renal Elimination/drug effects , Animals , Drug Interactions , Feces , Hydroxybenzoates/blood , Male , Mice , Molecular Structure , Neurodegenerative Diseases/prevention & control , Neuroprotective Agents/metabolism , Protein Isoforms
17.
Hepatogastroenterology ; 56(90): 328-34, 2009.
Article in English | MEDLINE | ID: mdl-19579592

ABSTRACT

BACKGROUND/AIMS: We aimed to assess liver fibrosis in biopsies from patients with chronic hepatitis C and relationship to different responses to interferon-beta-la. METHODOLOGY: 21 patients with chronic hepatitis C were divided into two groups randomly and treated with recombinant human interferon-beta-la (IFN-B-1a) or IFN-beta-1a plus ribavirin (RBV) for 24 weeks, then followed up for another 24 weeks. 42 liver biopsies of 21 patients before and after treatment respectively were evaluated on conventional histological assessment. Then we studied 21 patients liver biopsies by immunohistochemical analysis of alpha-smooth muscle actin (alpha-SMA) and collagen type III. RESULTS: A significant improvement in HAI fibrosis staging was detected after therapy in all sustained viral responders (SVR) and non-responders (NR) patients. The percentages of cases with HAI scores and fibrosis staging decreased obviously were 100.0% and 71.4% in SVR patients and 50.0% and 42.9% in NR patients. The patients with combination therapy or normal ALT on 48w would more often receive the HAI and fibrosis staging decrease. The significantly lower alpha-SMA-positive HSCs and mean expression level of collagen type III were detected in the post-treatment biopsies. The HAI, alpha-SMA, collagen type III values were significantly correlated with the values of the semiquantitative indexes of fibrosis. CONCLUSIONS: IFN-beta-1a therapy is effective for patients with chronic hepatitis C on liver histology regardless of viral response. The alpha-SMA-positive HSCs and collagen type III expression are responsible for liver fibrosis.


Subject(s)
Antiviral Agents/therapeutic use , Hepatic Stellate Cells/drug effects , Hepatitis C, Chronic/drug therapy , Interferon-beta/therapeutic use , Liver Cirrhosis/drug therapy , Ribavirin/therapeutic use , Adult , Biopsy , Collagen/drug effects , Drug Therapy, Combination , Female , Humans , Interferon beta-1a , Liver Function Tests , Logistic Models , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Treatment Outcome
18.
ISA Trans ; 94: 265-275, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31078296

ABSTRACT

According to cold heading process with overloaded craft, high-impact dynamic real-time measurement requirements, this paper presents researches on dynamic characteristics and optimization of PVDF piezoelectric film force sensor for steel ball cold heading forming quality monitoring, through the combination method of mechanism analysis, mathematical modeling, numerical simulation and experimental validation. The motivation and strategic objectives are to breakthrough dynamic time-varying impacting load measuring fundamental technologies in steel ball forging process. The structure of piezoelectric film force sensor is proposed. The theoretical calculation formula of natural frequency is deduced and calculated by using MATLAB software. The mechanical performance analysis on dynamic model and structural optimization simulation by FEM is carried out. In order to study the validity of the proposed method, a prototype of the sensor is fabricated. The static and dynamic calibration devices are designed to realize calibration experiments on the fabricated PVDF piezoelectric film force sensor. The differences among experimental value, simulation value and the theoretical value are given. The nonlinear error of the fabricated sensor is 0.197%. The sensor's first order natural frequency value is 5238 Hz. It is proved that the PVDF piezoelectric film force sensor has superior dynamic performance and high accuracy for measuring deformation in steel ball. The paper will provide important scientific basis and technical foundation to achieve superior performance steel ball.

19.
Wound Repair Regen ; 16(4): 576-81, 2008.
Article in English | MEDLINE | ID: mdl-18638277

ABSTRACT

Studies suggest a possible antiscarring effect of basic fibroblast growth factor (bFGF) during wound healing. However, little is known about the precise pathological mechanisms of bFGF. In particular, there is only limited information available about the mechanism of exogenous administration of bFGF to scar formation. To investigate the effect of bFGF on the hypertrophic scar in the rabbit ear model and to clarify the mechanisms of bFGF on treatment for scar in wound healing, the rabbit ear model of wound healing was created and treated topically with bFGF once daily for 3 months; then we examined the changes of macroscopic and histopathological characteristics of scars and the expression of collagen and collagenase-1 (matrix metalloproteinase-1). The results of macroscopic and histologic characteristics revealed a significant difference between scars treated with bFGF and control scars. The expression of collagen in the scars treated with bFGF was decreased, as compared with the scars treated with saline. Further study revealed that bFGF could remarkably enhance expression of matrix metalloproteinase-1. bFGF could improve the quality of wound healing and remarkably alleviate the scar in the rabbit ear model in wound healing, which suggests that bFGF exerted a net negative effecton scar formation in wound healing. The evidence should contribute to a better understanding of the biological activities of bFGF during hypertrophic scar formation.


Subject(s)
Cicatrix, Hypertrophic/pathology , Ear, External/injuries , Fibroblast Growth Factor 2/pharmacology , Wound Healing/drug effects , Animals , Blotting, Western , Female , Fibroblast Growth Factor 2/administration & dosage , Matrix Metalloproteinase 1/metabolism , Rabbits
20.
Zhonghua Yi Xue Za Zhi ; 88(2): 96-100, 2008 Jan 08.
Article in Zh | MEDLINE | ID: mdl-18353212

ABSTRACT

OBJECTIVE: To access the effect of pegylated interferon (PEGIFN) beta-1a on the reduction of liver fibrosis in chronic hepatitis C (HVC). METHODS: Twenty-one patients with chronic HVC were divided into two groups randomly and treated with recombinant human PEGIHN-beta-1a (n = 13) or PEGIHN-beta-1a plus ribavirin (RBV) (n = 8) for 24 weeks, and then followed up for another 24 weeks. The clinical manifestations were observed and the clinical effects were evaluated. Biopsy was conducted before and after the treatment to analyze the histological activity index (HAI) and staging of fibrosis according the modified Knodell scoring system. Immunohistochemical analysis was used to examine the levels of alpha-smooth muscle actin (alpha-SMA), marker of activation of hepatic stellate cells (HSCs), and collagen type III in the HSCs. RESULTS: Sustained viral response (SVR) was achieved in 7 patients, and end-of-treatment virologic response (ETVR) was achieved in 9 patients. The HAI after treatment was 4.3 +/- 2.2, significantly lower than that before treatment (6.6 +/- 2.2, t = 4.77, P < 0.01). The fibrosis score after treatment was 1.1 +/- 1.1, significantly lower than that before treatment (1.7 +/- 1.2, t = 1.92, P < 0.05). The alpha-SMA score after treatment was 14 +/- 8, significantly lower than that before treatment (20 +/- 11, t = 2.15, P < 0.05). The integrated light density of collagen type III after treatment was 10 +/- 10, significantly lower than that before treatment (16 +/- 12, t = 1.83, P < 0.05). The improvement levels of fibrosis, alpha-SMA score, and integrated light density of collagen type III of the patients with SVR were all better than those of the patients without SVR; however, the differences were all not significant. The patients with combination therapy, female patients, and the patients with the HCV RNA < 2 x 10(6) copies/ml before treatment all showed higher levels in histology response. HAI, alpha-SMA level, and collagen type III values were all significantly correlated with the values of the semiquantitative indexes of fibrosis (all P < 0.01). CONCLUSION: Resisting hepatitis virus C and inhibiting and reversing the fibrotic progress, IFN-beta-1a therapy improves the liver histology of chronic HVC regardless of the viral response.


Subject(s)
Hepatitis C, Chronic/drug therapy , Interferon-beta/therapeutic use , Liver Cirrhosis/drug therapy , Liver/drug effects , Actins/biosynthesis , Adult , Antiviral Agents/therapeutic use , Collagen Type III/biosynthesis , Female , Hepatitis C, Chronic/complications , Humans , Interferon beta-1a , Liver/pathology , Liver/virology , Liver Cirrhosis/etiology , Liver Cirrhosis/metabolism , Male , Middle Aged , Muscle, Smooth/chemistry , Ribavirin/therapeutic use , Treatment Outcome
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