ABSTRACT
OBJECTIVES: This study aimed to investigate the effect and the mechanism of recombinant human fibroblast growth factor 18 (rhFGF18) on postmenopausal osteoporosis. METHODS: The effect of rhFGF18 on the proliferation and apoptosis of osteoblasts and the mechanism underlying such an effect was evaluated using an oxidative stress model of the MC3T3-E1 cell line. Furthermore, ovariectomy was performed on ICR mice to imitate estrogen-deficiency postmenopausal osteoporosis. Bone metabolism and bone morphological parameters in the ovariectomized (OVX) mice were evaluated. RESULTS: The results obtained from the cell model showed that FGF18 promoted MC3T3-E1 cell proliferation by activating the extracellular signal-regulated kinase (ERK) and p38 instead of c-Jun N-terminal kinase (JNK). FGF18 also prevented cells from damage inflicted by oxidative stress via inhibition of apoptosis. After FGF18 administration, the expression level of anti-apoptotic protein Bcl-2 in the mice was upregulated, whereas those of the pro-apoptotic proteins Bax and caspase-3 were downregulated. Administering FGF18 also improved bone metabolism and bone morphological parameters in OVX mice. CONCLUSIONS: FGF18 could effectively prevent bone loss in OVX mice by enhancing osteoblastogenesis and protecting osteoblasts from oxidative stress-induced apoptosis.
Subject(s)
Apoptosis , Cell Proliferation , Disease Models, Animal , Fibroblast Growth Factors , Osteoblasts , Osteoporosis, Postmenopausal , Ovariectomy , Oxidative Stress , Recombinant Proteins , Animals , Fibroblast Growth Factors/pharmacology , Mice , Female , Apoptosis/drug effects , Recombinant Proteins/pharmacology , Osteoblasts/drug effects , Humans , Oxidative Stress/drug effects , Osteoporosis, Postmenopausal/prevention & control , Cell Proliferation/drug effects , Mice, Inbred ICR , Cell LineABSTRACT
Objective: To investigate the accuracy and efficiency of spine 2D/3D preoperative CT and intraoperative X-ray registration through a framework for spine 2D/3D single-vertebra navigation registration based on the fusion of dual-position image features. Methods: The preoperative CT and intraoperative anteroposterior (AP) and lateral (LAT) X-ray images of 140 lumbar spine patients who visited Huashan Hospital Affiliated to Fudan University from January 2020 to December 2023 were selected. In order to achieve rapid and high-precision single vertebra registration in clinical orthopedic surgery, a designed transformation parameter feature extraction module combined with a lightweight module of channel and spatial attention (CBAM) was used to accurately extract the local single vertebra image transformation information. Subsequently, the fusion regression module was used to complement the features of the anterior posterior (AP) and lateral (LAT) images to improve the accuracy of the registration parameter regression. Two 1Ć1 convolutions were used to reduce the parameter calculation amount, improve computational efficiency, and accelerate intraoperative registration time. Finally, the regression module outputed the final transformation parameters. Comparative experiments were conducted using traditional iterative methods (Opt-MI, Opt-NCC, Opt-C2F) and existing deep learning methods convolutional neural network (CNN) as control group. The registration accuracy (mRPD), registration time, and registration success rate were compared among the iterative methods. Results: Through experiments on real CT data, the image-guided registration accuracy of the proposed method was verified. The method achieved a registration accuracy of (0.81Ā±0.41) mm in the mRPD metric, a rotational angle error of 0.57Ā°Ā±0.24Ā°, and a translation error of (0.41Ā±0.21) mm. Through experimental comparisons on mainstream models, the selected DenseNet alignment accuracy was significantly better than ResNet as well as VGG (both P<0.05). Compared to existing deep learning methods [mRPD: (2.97Ā±0.99) mm, rotational angle error: 2.64Ā°Ā±0.54Ā°, translation error: (2.15Ā±0.41) mm, registration time: (0.03Ā±0.05) seconds], the proposed method significantly improved registration accuracy (all P<0.05). The registration success rate reached 97%, with an average single registration time of only (0.04Ā±0.02) seconds. Compared to traditional iterative methods [mRPD: (0.78Ā±0.26) mm, rotational angle error: 0.84Ā°Ā±0.57Ā°, translation error: (1.05Ā±0.28) mm, registration time: (35.5Ā±10.5) seconds], registration efficiency of the proposed method was significantly improved (all P<0.05). The dual-position study also compensated for the limitations in the single-view perspective, and significantly outperforms both the front and side single-view perspectives in terms of positional transformation parameter errors (both P<0.05). Conclusion: Compared to existing methods, the proposed CT and X-ray registration method significantly reduces registration time while maintaining high registration accuracy, achieving efficient and precise single vertebra registration.
Subject(s)
Imaging, Three-Dimensional , Lumbar Vertebrae , Tomography, X-Ray Computed , Humans , Retrospective Studies , Lumbar Vertebrae/diagnostic imaging , Neural Networks, Computer , Surgery, Computer-Assisted/methodsABSTRACT
Objective: To explore the clinical implication of tissue-related biomarkers in patients with acute aortic dissection (AAD). Methods: It was a cross-sectional study. Ten Stanford Type A AAD patients, who were diagnosed and surgically treated in the Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, from December 2018 to August 2019, were selected as the case group. Meanwhile, 10 patients with atherosclerotic heart disease, who underwent coronary artery bypass grafting (CABG), were selected as control group. The ascending aorta tissue specimens from patients of the two groups were collected during the operation. Four-dimensional non-standard quantitative proteomics technology (4D-LFQ) was used to detect the protein profile of ascending aorta tissue specimens of the two groups and to screen out differentially expressed proteins and analyze their biological functions. Precise quantification of the selected target proteins was achieved by parallel response monitoring (PRM). Results: A total of 3 985 proteins were identified by 4D-LFQ technology, among which 3 350 proteins could be quantified. There were 39 proteins were significantly upregulated and 47 proteins were significantly downregulated in AAD group. The results of biological function analysis showed that most of the differentially expressed proteins were located in the extracellular, and their functions were mainly involved in cell migration and proliferation, inflammatory cell activation, cell contraction, and muscle organ development. The 15 selected proteins underwent precise quantification by PRM, and the results showed that integrin α-Ć¢Ā Ā”b (ITGA2B), integrin α-M (ITGAM), integrin Ć-2 (ITGB2), integrin Ć-3 (ITGB3) were significantly upregulated in the ascending aorta tissue of AAD patients. Conclusion: ITGA2B, ITGAM, ITGB2, and ITGB3 are highly expressed in aortic tissues of patients with AAD, which may be used as biomarkers for the diagnosis of AAD patients.
Subject(s)
Aortic Dissection , Aorta , Biomarkers , Coronary Artery Bypass , Cross-Sectional Studies , HumansABSTRACT
The aim of this study was to examine the efficacy of combined immunization of hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine (HBVac) in blocking father-infant transmission of hepatitis B virus (HBV). Newborns positive at birth for blood HBV sur-face antigen (HBsAg) and/or HBV DNA were selected and immunized with HBIG combination HBVac. At 7 months, HBV markers and HBV DNA of each neonate were measured using electrochemiluminescence with the Cobas-e-411 Automatic Electrochemiluminescence Immuno-assay Analyzer and fluorescence quantitative polymerase chain reaction. Among all 7-month-old subjects, the negative conversion rates of HBV DNA and HBsAg were 48/61 (78.7%) and 19/41 (46.3%), respectively. Therefore, this study demonstrated that prompt combination injection of HBIG and HBVac can protect some of the HBV DNA- and/ or HBsAg-positive newborns from HBV.
Subject(s)
Fathers , Hepatitis B Vaccines/administration & dosage , Hepatitis B virus/immunology , Hepatitis B/prevention & control , Immunoglobulins/administration & dosage , Female , Hepatitis B/transmission , Humans , Infant, Newborn , MaleABSTRACT
Hailey-Hailey disease (HHD) is an autosomal dominant disorder in which the ATP2C1 gene has been implicated. Many mutations of this gene have been detected in HHD patients. To analyze such mutations in HHD and summarize all those identified in Chinese patients with this disease, we examined four familial and two sporadic cases and searched for case reports and papers by using the Chinese Biological Medicine Database and PubMed. HHD diagnoses were made based on clinical features and histopathological findings. Polymerase chain reaction and direct sequencing of the ATP2C1 gene were performed using blood samples from HHD patients, unaffected family members, and 120 healthy individuals. Three mutations were identified, including the recurrent mutation c.2126C>T (p.Thr709Met), and two novel missense mutations, c.2235_2236insC (p.Pro745fs*756) and c.689G>A (p.Gly230Asp). Considering our data, 81 different mutations have now been reported in Chinese patients with HHD. In cases of misannotation or duplication, previously published mutations were renamed according to a complementary DNA reference sequence. These mutations are scattered throughout the ATP2C1 gene, with no evident hotspots or clustering. It is of note that some reported "novel" mutations were in fact found to be recurrent. Our findings expand the range of known ATP2C1 sequence variants in this disease.
Subject(s)
Calcium-Transporting ATPases/genetics , Genetic Predisposition to Disease , Mutation , Pemphigus, Benign Familial/genetics , Adult , Asian People , Base Sequence , Case-Control Studies , Child , Female , Gene Expression , Genes, Dominant , Humans , Male , Middle Aged , Molecular Sequence Data , Pedigree , Pemphigus, Benign Familial/diagnosis , Pemphigus, Benign Familial/ethnology , Pemphigus, Benign Familial/pathology , Sequence Analysis, DNA , Terminology as TopicABSTRACT
We investigated 2 Chinese families with dyschromatosis symmetrica hereditaria (DSH) and search for mutations in the adenosine deaminase acting on RNA1 (ADAR1) gene in these 2 pedigrees. We performed a mutation analysis of the ADAR1 gene in 2 Chinese families with DSH and reviewed all articles published regarding ADAR1 mutations reported since 2003 by using PubMed. By direct sequencing, a 2-nucleotide AG deletion, 2099-2100delAG, was found in family 1, and a CĆ¢ĀĀT mutation was identified at nucleotide 1420 that changed codon 474 from arginine to a translational termination codon in family 2. Two different pathogenic mutations were identified, c.2099-2100delAG and c.1420C>T, the former being a novel mutation, and the latter previously reported in 3 other families with DSH. To date, a total of 110 mutations in the ADAR1 gene have been reported, and 10 of them were recurrent; the mutations R474X, R1083C, R1096X, and R1155W might be the DSH-related hotspots.
Subject(s)
Adenosine Deaminase/genetics , Mutation , Pigmentation Disorders/congenital , Adolescent , Adult , Child , China , Female , Genes, Dominant , Humans , Male , Pedigree , Pigmentation Disorders/diagnosis , Pigmentation Disorders/genetics , RNA-Binding ProteinsABSTRACT
OBJECTIVE: To establish and develop a reliable and simple Real-time PCR assay with high resolution melting (Real-time PCR-HRM) method for detection epidermal growth factor (EGFR) and BIM mutation of lung cancer and looking for effective targeted drugs to control lung cancer. PATIENTS AND METHODS: A total of 6858 participants (2538 cases with lung cancer and 4275 healthy controls who took part in the study by doing the physical examination in Shanghai Xuhui community) were recruited in the study. Clinical characteristics and 5 ml peripheral blood were collected from each participant, and the DNA has been extracted, which were determined the EGFR and BIM mutation by Real-time PCR-HRM. Data were recorded and Statistical analyses. RESULTS: All samples completed the study. BIM deletion polymorphism was no related with age, sex, and smoking or EGFR mutation. CONCLUSIONS: There were no relations among BIM deletion polymorphism, EGFR mutation or lung cancer risk. HRM is a novel procedure and provides rapid, sensitive, specific and simultaneous detection for gene mutation of cancer patients for predicting the efficacy of targeted therapy.
Subject(s)
Bcl-2-Like Protein 11/genetics , ErbB Receptors/genetics , Lung Neoplasms/genetics , Real-Time Polymerase Chain Reaction , China , Humans , MutationABSTRACT
Surface enhanced infrared reflection-absorption spectroscopy with an attentuated total reflection configuration (ATR-SEIRAS) was used for the first time to identify the intermediates of the oxygen reduction reaction (ORR) on gold electrodes. Our study employed a Au thin-film electrode in acidic and alkaline solutions. In alkaline solutions, a potential dependent band at 1268 cm(-1), which we assigned to the antisymmetric bending mode of OOH of adsorbed HO2-, was observed between 0.1 and -0.6 V versus Ag|AgCl, Cl-, exactly in the potential range where the ORR occurred. The assignment was supported by our isotope exchange experiment. The adsorbed HO2- is a reaction intermediate in the 4e- serial mechanism. In acidic solutions, there was only a very weak band at the same position, reflecting the fast protonation of HO2-. This finding may imply that the interaction between HO2- and Au surfaces is very weak in acidic solutions, in agreement with the observed 2e- reduction mechanism.
ABSTRACT
We synthesized a new class of O2 electrocatalysts with a high activity and very low noble metal content. They consist of Pt monolayers deposited on the surfaces of carbon-supported nonnoble metal-noble metal core-shell nanoparticles. These core-shell nanoparticles were formed by segregating the atoms of the noble metal on to the nanoparticles' surfaces at elevated temperatures. A Pt monolayer was deposited by galvanic displacement of a Cu monolayer deposited at underpotentials. The mass activity of all the three Pt monolayer electrocatalysts investigated, viz., Pt/Au/Ni, Pt/Pd/Co, and Pt/Pt/Co, is more than order of magnitude higher than that of a state-of-the-art commercial Pt/C electrocatalyst. Geometric effects in the Pt monolayer and the effects of PtOH coverage, revealed by electrochemical data, X-ray diffraction, and X-ray absorption spectroscopy data, appear to be the source of the enhanced catalytic activity. Our results demonstrated that high-activity electrocatalysts can be devised that contain only a fractional amount of Pt and a very small amount of another noble metal.
ABSTRACT
Phages with high affinity to the P20 protein of rice stripe virus (RSV) were enriched from phage-displayed random 12-mer peptide library after three rounds of phage display screening. Nine different peptides from the enriched library were selected by enzyme-linked immunosorbent assay (ELISA). The P20 protein from raw extracts of rice leaves infected with RSV could be detected by those 9 peptides displayed on the phage, which suggested that a peptide could be an effective tool for diagnosis of RSV in rice and planthopper. Circular dichroism (CD) spectra of P20 fusion proteins with the binding phages and non-binding phages showed that the conformation of P20 protein was changed after binding to each of the 9 selected 12-mer peptides, which suggested that these peptides might disrupt the function of the P20 protein. Thereafter, those peptides might be used to develop plant resistance and disrupt virus transmission. Three of the 12-mer peptide genes were fused with the glutathione-S-transferase (GST) gene in the vector pGEX 3X. The fusion proteins were obtained from an Escherichia coli expression system and purified. The fusion proteins might have a potential to develop a plant peptide-based resistance to its pathogens and virus diagnosis. It also provided a tool (i) to confirm the inhibition of the function of P20 protein by the fusion peptides in vivo, and (ii) to detect the function of P20 protein and the interaction between the virus and its vector.
Subject(s)
Tenuivirus/genetics , Viral Proteins/chemistry , Electrophoresis, Polyacrylamide Gel , Peptide Library , Peptides/isolation & purification , Peptides/metabolism , Protein Conformation , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/isolation & purification , Tenuivirus/chemistryABSTRACT
This paper reports fourteen cases of advanced and recurrent gynecologic cancers treated with prolonged arterial perfusion chemotherapy by catheterization of both internal iliac arteries through femoral arteriopuncture under X-ray. The immediate effective rate was 78.5%, follow-up rate 100%. By this technique anticancer drugs can be selectively injected into vessels supplying the tumors. The drug is concentrated within the tumor resulting in longterm better local effects, and fewer general side reactions, and a much higher dose than that which could be given conventionally. This technique is considered as a new route of treatment in gynecologic tumors.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ovarian Neoplasms/drug therapy , Uterine Cervical Neoplasms/drug therapy , Adult , Aged , Bleomycin/administration & dosage , Carcinoma, Squamous Cell/drug therapy , Cisplatin/administration & dosage , Female , Humans , Iliac Artery , Infusions, Intra-Arterial , Middle Aged , Mitomycin/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Vincristine/administration & dosage , Vulvar Neoplasms/drug therapyABSTRACT
We investigated the oxygen-reduction reaction (ORR) on Pd monolayers on various surfaces and on Pd alloys to obtain a substitute for Pt and to elucidate the origin of their activity. The activity of Pd monolayers supported on Ru(0001), Rh(111), Ir(111), Pt(111), and Au(111) increased in the following order: Pd/Ru(0001) < Pd/Ir(111) < Pd/Rh(111) < Pd/Au(111) < Pd/Pt(111). Their activity was correlated with their d-band centers, which were calculated using density functional theory (DFT). We found a volcano-type dependence of activity on the energy of the d-band center of Pd monolayers, with Pd/Pt(111) at the top of the curve. The activity of the non-Pt Pd2Co/C alloy electrocatalyst nanoparticles that we synthesized was comparable to that of commercial Pt-containing catalysts. The kinetics of the ORR on this electrocatalyst predominantly involves a four-electron step reduction with the first electron transfer being the rate-determining step. The downshift of the d-band center of the Pd "skin", which constitutes the alloy surface due to the strong surface segregation of Pd at elevated temperatures, determined its high ORR activity. Additionally, it showed very high methanol tolerance, retaining very high catalytic activity for the ORR at high concentrations of methanol. Provided its stability is satisfactory, this catalyst might possibly replace Pt in fuel-cell cathodes, especially those of direct methanol oxidation fuel cells (DMFCs).