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1.
J Tissue Viability ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38697891

ABSTRACT

BACKGROUND: Patients with cancer are susceptible to pressure injuries, which accelerate deterioration and death. In patients with post-acute cancer, the risk of pressure injury is ignored in home or community settings. OBJECTIVE: To develop and validate a community-acquired pressure injury risk prediction model for cancer patients. METHODS: All research data were extracted from the hospital's electronic medical record system. The identification of optimal predictors is based on least absolute shrinkage and selection operator regression analysis combined with clinical judgment. The performance of the model was evaluated by drawing a receiver operating characteristic curve and calculating the area under the curve (AUC), calibration analysis and decision curve analysis. The model was used for internal and external validation, and was presented as a nomogram. RESULTS: In total, 6257 participants were recruited for this study. Age, malnutrition, chronic respiratory failure, body mass index, and activities of daily living scores were identified as the final predictors. The AUC of the model in the training and validation set was 0.87 (95 % confidence interval [CI], 0.85-0.89), 0.88 (95 % CI, 0.85-0.91), respectively. The model demonstrated acceptable calibration and clinical benefits. CONCLUSIONS: Comorbidities in patients with cancer are closely related to the etiology of pressure injury, and can be used to predict the risk of pressure injury. IMPLICATIONS FOR PRACTICE: This study provides a tool to predict the risk of pressure injury for cancer patients. This suggests that improving the respiratory function and nutritional status of cancer patients may reduce the risk of community-acquired pressure injury.

2.
Article in English | MEDLINE | ID: mdl-38723775

ABSTRACT

PURPOSE: Radiation-induced dermatitis (RD) is a common side effect of therapeutic ionizing radiation that can severely affect patient quality of life. This study aimed to develop a risk prediction model for the occurrence of RD in patients with cervical carcinoma undergoing chemoradiotherapy using electronic medical records (EMRs). METHODS: Using electronic medical records, the clinical data of patients who underwent simultaneous radiotherapy and chemotherapy at a tertiary cancer hospital between 2017 and 2022 were retrospectively collected, and the patients were divided into two groups: a training group and a validation group. A predictive model was constructed to predict the development of RD in patients who underwent concurrent radiotherapy and chemotherapy for cervical cancer. Finally, the model's efficacy was validated using a receiver operating characteristic (ROC) curve. RESULTS: The incidence of radiation dermatitis was 89.5% (560/626) in the entire cohort, 88.6% (388/438) in the training group, and 91.5% (172/188) in the experimental group. The nomogram was established based on the following factors: age, the days between the beginning and conclusion of radiotherapy, the serum albumin (ALB) after chemoradiotherapy, the use of single or multiple drugs for concurrent chemotherapy, and the total dose of afterloading radiotherapy. Internal and external verification indicated that the model had good discriminatory ability. Overall, the model achieved an AUC of .66. CONCLUSIONS: The risk of RD in patients with cervical carcinoma undergoing chemoradiotherapy is high. A risk prediction model can be developed for RD in cervical carcinoma patients undergoing chemoradiotherapy, based on over 5 years of EMR data from a tertiary cancer hospital.

3.
Appl Opt ; 63(8): 1961, 2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38568635

ABSTRACT

This publisher's note reports a correction in Appl. Opt.63, 1153 (2024)APOPAI0003-693510.1364/AO.513837.

4.
Front Public Health ; 12: 1289498, 2024.
Article in English | MEDLINE | ID: mdl-38645460

ABSTRACT

Background and objective: Nurses have an essential role in dealing with public health emergencies (PHE). This study explored the knowledge, attitude, and practice (KAP) towards preventing occupational exposure in PHE among nurses in Wuhan. Methods: This cross-sectional study was conducted in May 2023 to assess the KAP of nurses in Wuhan, China. Questionnaires were created and distributed to evaluate the KAP of nurses and explore the factors associated with KAP. Univariate and multivariate logistic regression analyses were used to assess the association between baseline demographic characteristics and KAP, and structural equation modeling (SEM) was used to explore complex relationships and causal pathways among relevant factors. Results: A total of 440 valid questionnaires were collected. The mean knowledge, attitude, and practice scores were 11.84 ± 2.37, 39.87 ± 3.10, and 44.05 ± 3.76, respectively. The univariate and multivariate logistic regression analyses revealed that age >50 years old (p = 0.039), working experience of 1-3 years (p = 0.060) and 4-6 years (p = 0.024), participation in PHE training, and scene rescue (p < 0.001) were significantly associated with knowledge score. In addition, the attitude of the nurses was significantly related to knowledge scores (p = 0.002). Moreover, practice was significantly associated with knowledge scores (p = 0.005) and attitude scores (p < 0.001). The correlation analysis showed that the practice was significantly associated with knowledge (r = 0.336, p < 0.001) and attitude (r = 0.449, p < 0.001). Conclusion: Nurses exhibited moderate knowledge, relatively positive attitude, and practice, which needed to be improved regarding occupational exposure in PHE. The practice of the nurses could be promoted by paying more attention to the working experience, participation in training and scene rescue in PHE, and their knowledge and attitude.


Subject(s)
Health Knowledge, Attitudes, Practice , Occupational Exposure , Humans , Cross-Sectional Studies , China , Female , Male , Adult , Surveys and Questionnaires , Middle Aged , Occupational Exposure/prevention & control , Emergencies , Public Health , Nurses/psychology , Nurses/statistics & numerical data
5.
Appl Opt ; 63(4): 1153-1159, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38437414

ABSTRACT

A single-double-band switchable circular polarization filter based on surface plasmon resonance exhibits significant potential for applications in fields such as communication and sensing due to its adjustable, low-cost, and easy integration features. In this study, we propose a bi-layer rod nanostructure and use FEM simulation to study the transmission spectra of the structure. The results demonstrate that the structure exhibits both single- and double-band circular polarization filtering effects, which can be switched by varying geometric parameters such as the distance between the two layers and the width of nanorods. Furthermore, the filtering effects of both single- and double-band are highly dependent on the length of the nanorods, with average extinction rates reaching 486 and 2020/129, respectively; the operating bandwidths (defined as extinction ratio >10) can reach 170 nm and 35 nm/70 nm, respectively. The underlying physical mechanisms are clarified by analyzing the electric dipole, magnetic dipole resonance modes, and induced chiral fields on nanostructures.

7.
Heliyon ; 10(3): e25080, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38356524

ABSTRACT

Objective: RNA-binding proteins (RBPs) have been recently proven to be involved in the pathogenesis of several diseases. However, few studies elaborated RBPs in regulating osteoarthritis. This study aims to define the function and mechanism of RBPs-PUM2 in chondrocyte apoptosis during osteoarthritis. Methods: Cartilage tissue samples and human juvenile chondrocyte cell line C28/I2 were collected for further study. PUM2 expression in the human tissues and cells was determined using qRT-PCR. Chondrocyte viability and apoptosis were determined by MTT and flow cytometry. ROS generation was determined by flow cytometry. The regulation of PUM2 on FOXO3 translation was evaluated by RNA immunoprecipitation, RNA pull-down, and Luciferase gene reporter analysis. Results: PUM2 is upregulated in both cartilage tissue of osteoarthritis patients and IL-1ß-stimulated chondrocytes. PUM2 overexpression reduces cell viability and promotes cell apoptosis and ROS generation of chondrocytes. PUM2 silencing increases cell viability and ameliorates cell apoptosis as well as ROS generation in chondrocytes induced by IL-1ß. PUM2 inhibits FOXO3 expression via binding its mRNA 3'-UTR. PUM2 forms a signaling axis with FOXO3 in IL-1ß induced chondrocyte damage. Conclusion: PUM2 is upregulated in cartilage tissue of osteoarthritis and positively regulates chondrocytes apoptosis through controlling FOXO3 protein expression.

8.
iScience ; 27(1): 108702, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38205260

ABSTRACT

Immunogenic cell death (ICD) can activate the anticancer immune response and its occurrence requires high reliance on oxidative stress. Inducing mitochondrial reactive oxygen species (ROS) is a desirable capability for ICD inducers. However, in the category of ICD-associated drugs, numerous reported ICD inducers are a series of anthracyclines and weak in ICD induction. Herein, a mitochondria-targeting dihydroartemisinin derivative (T-D) was synthesized by conjugating triphenylphosphonium (TPP) to dihydroartemisinin (DHA). T-D can selectively accumulate in mitochondria to trigger ROS generation, leading to the loss of mitochondrial membrane potential (ΔΨm) and ER stress. Notably, T-D exhibits far more potent ICD-inducing properties than its parent compound. In vivo, T-D-treated breast cancer cell vaccine inhibits metastasis to the lungs and tumor growth. These results indicate that T-D is an excellent ROS-based ICD inducer with the specific function of trigging vigorous ROS in mitochondria and sets an example for incorporating artemisinin-based drugs into the ICD field.

9.
Apoptosis ; 29(3-4): 331-343, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37848671

ABSTRACT

Tumor immune escape is an important manner for colon cancer to escape effective killing by immune system. Currently, the immune checkpoint PD-1/PD-L1-targeted immunotherapy has emerged as a promising therapeutic strategy in colon cancer. Here, present work aims to investigate the biological function of N6-methyladenosine (m6A) reader insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in regulating colon cancer's immune escape and CD8 + T cells-mediated tumor cytotoxicity and apoptosis. Results illustrated that IGF2BP1 was closely correlated to the colon cancer patients' poor clinical outcome. Functionally, upregulation of IGF2BP1 suppressed the CD8+ T-cells mediated antitumor immunity through reducing their tumor cytotoxicity. Mechanistically, MeRIP-Seq revealed that programmed death ligand 1 (PD-L1) mRNA had a remarkable m6A modified site on 3'-UTR genomic. Moreover, PD-L1 acted as the target of IGF2BP1, which enhanced the stability of PD-L1 mRNA. Overall, these results indicated that IGF2BP1 targeted PD-L1 to accelerate the immune escape in colon cancer by reducing CD8 + T cells-mediated tumor cytotoxicity in m6A-dependent manner. The findings demonstrate the potential of m6A-targeted immune checkpoint blockade in colon cancer, providing a novel insight for colon cancer immune escape and antitumor immunity in further precise treatment.


Subject(s)
CD8-Positive T-Lymphocytes , Colonic Neoplasms , Humans , CD8-Positive T-Lymphocytes/metabolism , B7-H1 Antigen/genetics , Apoptosis/genetics , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , RNA, Messenger/metabolism
10.
Front Immunol ; 14: 1302336, 2023.
Article in English | MEDLINE | ID: mdl-38143758

ABSTRACT

Background: Human adipose tissue-derived stem cells (hADSCs) exert potent immunosuppressive effects in the allogeneic transplantation treatment. In mouse model of allergic rhinitis (AR), ADSCs partially ameliorated AR. However, no study has evaluated the potential therapeutic effects of hADSC-derived extracellular vesicles (hADSC-EVs) on AR. Methods: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce AR. One day after the last nasal drop, each group received phosphate buffered saline (PBS) or hADSC-EVs treatment. Associated symptoms and biological changes were then assessed. Results: hADSC-EV treatment significantly alleviated nasal symptoms, and reduced inflammatory infiltration. Serum levels of OVA-specific IgE, interleukin (IL)-4 and interferon (IFN)-γ were all significantly reduced. The mRNA levels of IL-4 and IFN-γ in the spleen also changed accordingly. The T helper (Th)1/Th2 cell ratio increased. The treatment efficacy index of hADSC-EV was higher than that of all human-derived MSCs in published reports on MSC treatment of AR. ADSC-EVs exhibited a greater therapeutic index in most measures when compared to our previous treatment involving ADSCs. Conclusion: These results demonstrated that hADSC-EVs could ameliorate the symptoms of AR by modulating cytokine secretion and Th1/Th2 cell balance. hADSC-EVs could potentially be a viable therapeutic strategy for AR. Further animal studies are needed to elucidate the underlying mechanisms and to optimize potential clinical protocols.


Subject(s)
Cytokines , Rhinitis, Allergic , Female , Humans , Animals , Mice , Immunoglobulin E , T-Lymphocytes, Helper-Inducer , Stem Cells
11.
Opt Lett ; 48(19): 5001-5004, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37773370

ABSTRACT

A spatial light modulator (SLM) is incorporated into a focused laser differential interferometer (FLDI) to generate a nonlinear array of beams, and this setup is used to measure the power spectral density of a Mach-1.5, underexpanded jet of air. The results are compared with measurements from a 1-point FLDI to assess the feasibility of using SLMs in FLDI to serve as dynamic diffractive elements for generating beam arrays of any shape. The spectra comparison illustrates that spatial light modulated-FLDI (SLM-FLDI) detects similar spectral profiles to that of 1-point FLDI, especially dominant frequencies in the jet. SLM-FLDI could provide a useful expansion of FLDI capabilities.

12.
Int J Biol Macromol ; 253(Pt 1): 126658, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37660865

ABSTRACT

In tissue engineering, scaffold microstructures and mechanical cues play a significant role in regulating stem cell differentiation, proliferation, and infiltration, offering a promising strategy for osteochondral tissue repair. In this present study, we aimed to develop a facile method to fabricate an acellular hydrogel scaffold (AHS) with tunable mechanical stiffness and microstructures using carboxymethyl cellulose (CMC). The impacts of the degree of crosslinking, crosslinker length, and matrix density on the AHS were investigated using different characterization methods, and the in vitro biocompatible of AHS was also examined. Our CMC-based AHS showed tunable mechanical stiffness ranging from 50 kPa to 300 kPa and adjustable microporous size between 50 µm and 200 µm. In addition, the AHS was also proven biocompatible and did not negatively affect rabbit bone marrow stem cells' dual-linage differentiation into osteoblasts and chondrocytes. In conclusion, our approach may present a promising method in osteochondral tissue engineering.


Subject(s)
Mesenchymal Stem Cells , Tissue Engineering , Animals , Rabbits , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Carboxymethylcellulose Sodium , Hydrogels/pharmacology
13.
Biomarkers ; 28(6): 519-530, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37382580

ABSTRACT

INTRODUCTION: Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with heart failure and stroke, leading sometimes to death. But the pathogenesis of AF remains unclear. Numerous studies have investigated whether the connexin 40 (Cx40) polymorphisms influences the risk of AF, but the results are controversial. METHODS: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to examine the existence of genetic associations between the Cx40 polymorphisms and the risk of AF. All relevant studies were screened and meta-analyzed using Review Manager 5.0. RESULTS: A total of 12 studies, including 10 studies for -44 polymorphism (rs35594137) and 4 studies for -26 polymorphism (rs10465885), were identified for the meta-analysis. For -44 polymorphism, the results showed a significantly increased risk of AF in the five genetic models in the overall analysis. Furthermore, in subgroup analysis, increased AF risks were also observed in Asian and non-Asian populations. For -26 polymorphism, the overall OR revealed an increased risk of AF in dominant model. In subgroup analysis, increased AF risk was only found in recessive genetic model of the Asian population. CONCLUSIONS: The Cx40 polymorphisms were positively associated with AF in both populations, especially on -44 polymorphism.


Subject(s)
Atrial Fibrillation , Connexins , Humans , Atrial Fibrillation/complications , Connexins/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Gap Junction alpha-5 Protein
14.
BMC Infect Dis ; 23(1): 312, 2023 May 09.
Article in English | MEDLINE | ID: mdl-37161385

ABSTRACT

BACKGROUND: With the measles vaccine coverage rate gradually increasing, adult patients' epidemiological and clinical characteristics have changed. AIMS: To analyze the clinical characteristics of adult measles patients in Beijing Youan Hospital. METHODS: We retrospectively reviewed the electronic medical records of 818 patients diagnosed with measles at Beijing Youan Hospital between June 2010 and October 2021. We divided all hospitalized patients into two demographics groups, using 14 years of age as the cut-off. RESULTS: Of the adult inpatients, 110 (74.83%) were aged 20-40. There was an overall peak incidence in 2014, and yearly peaks came in April. Fever, cough, erythema, and Koplik's spots were present in 79.59%, 82.1%, 99.3%, and 59.8% of the adult group, respectively, compared to 75.26%, 92.0%, 99.9%, and 39.0% of the pediatric group. Decreased lymphocytes and hepatic impairment were common in adults. The adult group's median level of C-reactive protein was higher than that of the pediatric group (p < 0.05). The positive rate of measles antibody (IgM) detection was 64.6% in the adults and 78.8% in the pediatric group (p < 0.05). Of the adults, 46.9%, 8.8%, and 66% had pneumonia, gastroenteritis, and antibiotic use, compared to 89.6%, 2.7%, and 83.2% of the pediatric patients. The duration of symptoms before admission and the average length of hospital stay was approximately six days in both groups. CONCLUSIONS: Koplik's spots are more likely to be detected by clinicians in adult patients admitted to the hospital. Active surveillance is helpful for adults who are negative for IgM on admission. Although the proportion of adult measles patients with liver injury is high, the disease is generally mild. Measles significantly impacts peripheral blood lymphocytes in adults, but adults are at lower risk of concurrent pneumonia than the pediatric group. Clinicians need to pay attention to the appropriate use of antibiotics. Expanding the coverage of the measles vaccination in high-risk areas is beneficial for preventing measles in adults.


Subject(s)
Inpatients , Measles , Adult , Humans , Child , Adolescent , Retrospective Studies , Measles/epidemiology , Measles/prevention & control , Measles Vaccine/therapeutic use , Anti-Bacterial Agents , Immunoglobulin M
15.
Int J Biol Macromol ; 242(Pt 3): 125041, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37236561

ABSTRACT

The introduction of active groups from biomass is currently the most promising alternative method for increasing the adsorption effect of dyes. In this study, modified aminated lignin (MAL) rich in phenolic hydroxyl and amine groups was prepared by amination and catalytic grafting. The factors influencing the modification conditions of the content of amine and phenolic hydroxyl groups were explored. Chemical structural analysis results confirmed that MAL was successfully prepared using a two-step method. The content of phenolic hydroxyl groups in MAL significantly increased to 1.46 mmol/g. MAL/sodium carboxymethylcellulose (NaCMC) gel microspheres (MCGM) with enhanced methylene blue (MB) adsorption capacity owing to the formation of a composite with MAL were synthesized by a sol-gel process followed by freeze-drying and using multivalent cations Al3+ as cross-linking agents. In addition, the effects of the MAL to NaCMC mass ratio, time, concentration, and pH on the adsorption of MB were explored. Benefiting from a sufficient number of active sites, MCGM exhibited an ultrahigh adsorption capacity for MB removal, and the maximum adsorption capacity was 118.30 mg/g. These results demonstrated the potential of MCGM for wastewater treatment applications.


Subject(s)
Methylene Blue , Water Pollutants, Chemical , Methylene Blue/chemistry , Lignin/chemistry , Carboxymethylcellulose Sodium/chemistry , Microspheres , Water Pollutants, Chemical/chemistry , Adsorption , Coloring Agents/chemistry , Amines , Kinetics , Hydrogen-Ion Concentration
16.
Materials (Basel) ; 16(7)2023 Mar 29.
Article in English | MEDLINE | ID: mdl-37049009

ABSTRACT

To study the penetration and cratering effect of reactive material composite jets, a series of experiments are carried out for the shaped charge (SC) with different composite liners damaging steel targets. The inner layer of composite liners is metal and the outer one is a polytetrafluoroethylene/aluminum (PTFE/Al) reactive material. Copper (Cu), titanium (Ti) and Al inner liners are used in this paper. The reactive material liner is composed of 73.5 wt.% PTFE and 26.5 wt.% Al powder through mass-matched ratios. Reactive material composite liners are prepared through machining, cold pressing and a sintering process. The SC mainly consists of a case, a composite liner, high-energy explosive and an initiator. The steel target is steel 45#, with a thickness of 66 mm. A standoff of 1.0 CD (charge diameter) is selected to conduct the penetration experiments. The experimental results show that when the inner layer of the composite liner is composed of Ti and Al, the hole diameters on the steel target formed by the reactive material composite jet are significantly larger than that of the inner Cu liner. By introducing the initiation delay time (τ) and detonation-like reaction model of PTFE/Al reactive materials, an integrated numerical simulation algorithm of the penetration and detonation-like effects of reactive material composite jets is realized. Numerical simulations demonstrate that the initial penetration holes on the steel targets are enlarged under the detonation-like effects of PTFE/Al reactive materials, and the simulated perforation sizes are in good agreement with the experimental results.

17.
IEEE J Biomed Health Inform ; 27(7): 3513-3524, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37058372

ABSTRACT

To accurately diagnose pneumonia patients on a limited annotated chest X-ray image dataset, a prior knowledge-based active attention network (PKA2-Net1) was constructed. The PKA2-Net uses improved ResNet as the backbone network and consists of residual blocks, novel subject enhancement and background suppression (SEBS) blocks and candidate template generators, where template generators are designed to generate candidate templates for characterizing the importance of different spatial locations in feature maps. The core of PKA2-Net is SEBS block, which is proposed based on the prior knowledge that highlighting distinctive features and suppressing irrelevant features can improve the recognition effect. The purpose of SEBS block is to generate active attention features without any high-level features and enhance the ability of the model to localize lung lesions. In SEBS block, first, a series of candidate templates T with different spatial energy distributions are generated and the controllability of the energy distribution in T enables active attention features to maintain the continuity and integrity of the feature space distributions. Second, Top-n templates are selected from T according to certain learning rules, which are then operated by a convolution layer for generating supervision information that can guide the inputs of SEBS block to form active attention features. We evaluated the PKA2-Net on the binary classification problem of identifying pneumonia and healthy controls on a dataset containing 5856 chest X-ray images (ChestXRay2017), the results showed that our method can achieve 97.63% accuracy and 0.9872 sensitivity.


Subject(s)
Pneumonia , Thorax , Humans , X-Rays , Knowledge , Knowledge Bases , Pneumonia/diagnostic imaging
18.
Chem Commun (Camb) ; 59(35): 5221-5224, 2023 Apr 27.
Article in English | MEDLINE | ID: mdl-37017275

ABSTRACT

We report a fascinating solid-phase synthesis of ultra-small CuMo solid solution alloy nanoclusters (2.1 nm) anchored on electrospun carbon nanofibers (CuMo/CNFs). By tuning the weight ratio of Cu and Mo, the optimized Cu2Mo1/CNFs achieves excellent CO2RR performance with a high faradaic efficiency (FE) of 84.5% for C2+ products and an FEethanol of 75.7%. In situ characterization demonstrates that the Cu2Mo1 alloy can strengthen the adsorption of the crucial intermediate and promote C-C coupling, leading to high selectivity and efficiency for C2+ products.

19.
Bioorg Chem ; 134: 106424, 2023 05.
Article in English | MEDLINE | ID: mdl-36868126

ABSTRACT

Cell-penetrating peptides (CPPs) are prominent scaffolds for drug developments and related research, particularly the endocytic delivery of biomacromolecules. Effective cargo release from endosomes prior to lysosomal degradation is a crucial step, where the rational design and selection of CPPs remains a challenge and calls for deeper mechanistic understandings. Here, we have investigated a strategy of designing CPPs that selectively disrupt endosomal membranes based on bacterial membrane targeting sequences (MTSs). Six synthesized MTS peptides all exhibit cell-penetrating abilities, among which two d-peptides (d-EcMTS and d-TpMTS) are able to escape from endosomes and localize at ER after entering the cell. The utility of this strategy has been demonstrated by the intracellular delivery of green fluorescent protein (GFP). Together, these results suggest that the large pool of bacterial MTSs may be a rich source for the development of novel CPPs.


Subject(s)
Cell-Penetrating Peptides , Cell-Penetrating Peptides/chemistry , Endosomes/chemistry , Endosomes/metabolism
20.
Br J Haematol ; 202(3): 623-635, 2023 08.
Article in English | MEDLINE | ID: mdl-36951360

ABSTRACT

Hereditary factor VII (FVII) deficiency is a rare recessive bleeding disorder with an estimated prevalence of 1/500 000. We had investigated 50 unrelated Chinese patients with FVII deficiency and identified, in total, 25 mutations, including 18 missense mutations and 5 splicing mutations, on the F7 gene. The nucleotide transition c.1224T>G (p.His408Gln) in exon 9 constitutes a hotspot of mutation, with 19 patients harbouring this genetic variance. Few patients were homozygous or compound heterozygous for deleterious mutations, such as non-sense mutations, large insertion or deletions, indicating that complete deficiency of FVII may not be compatible with life. The eight novel mutations identified in the study, including one small deletion (p.Glu49GlyfsTer101), three type I missense mutations, p.Cys238Phe, p.Gly420Asp, p.Ala252Val and four type II missense mutations, p.Val336Met, p.Ser342Gly, p.Gly432Ser and p.Ile213Asn, were further analysed by in vitro expression and functional studies. The laboratory phenotype and structural analysis confirmed the functional consequence of p.Ile213Asn mutation involving cleavage and activation site. The molecular dynamic simulations and binding energy calculations along with functional probing of p.Gly432Ser mutation revealed the critical role of residue Gly432 in the binding between activated factor VII (factor VIIa) and tissue factor.


Subject(s)
East Asian People , Factor VII Deficiency , Factor VII , Humans , East Asian People/genetics , Factor VII/genetics , Factor VII Deficiency/ethnology , Factor VII Deficiency/genetics , Factor VIIa , Genotype , Mutation
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