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1.
Neurol Sci ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39090356

ABSTRACT

BACKGROUND: It is debatable whether the area of substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is related to Parkinson's disease (PD) severity. Iron deposition, which is associated with the formation of SN+, may have different effects on dopamine nerve function as PD progresses. However, little research has explored the association between the SN + area and disease severity of PD in stages. METHODS: 612 PD patients with sufficient bone window were retrospectively included from a PD database, and disease severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) scores. Based on the Hoehn and Yahr (H-Y) scale, we classified the patients into seven groups (H-Y stage 1, 1.5, 2, 2.5, 3, 4, and 5) and then analyzed the correlations between the SN + area and the UPDRS scores separately. RESULTS: Our results indicated a U-shaped relationship between the initial-SN + area and disease severity in PD: In the H-Y stage 1 group, the initial-SN + area was negatively correlated with the UPDRS total score (r = - 0.456, p < 0.001) and UPDRS-III score (r = - 0.497, p < 0.001). No correlation was observed in the groups of H-Y stages 1.5, 2, and 2.5. In the groups of H-Y stage ≥ 3, the initial-SN + area was positively correlated with the UPDRS total score and UPDRS-III score, with strongest correlation in the H-Y stage 5 group (all p values < 0.05). Moreover, the larger SN + area and average SN + area showed a similar evolutionary trend of correlation with UPDRS total score and UPDRS-III score. CONCLUSIONS: Our study indicated a U-shaped correlation between the SN + area with the UPDRS total score and UPDRS-III score as H-Y stage progressed. The evolution of the correlation may reflect the evolution of underlying pathological mechanisms related to iron deposition in the substantia nigra.

2.
Heliyon ; 10(13): e34220, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39091930

ABSTRACT

Background: Colorectal signet-ring cell carcinoma (SRCC) is a rare subtype of malignant adenocarcinoma, accounting for approximately 1 % of colorectal cancer (CRC) cases. Its biomarkers and molecular characteristics remain controversial, and there are no specific therapeutic targets or strategies for its clinical treatment. Methods: A retrospective study was conducted between January 2010 and December 2021. 1058 colorectal cancer cases from the Sun Yat-sen University Cancer Center and 489 cases from the Tumor Genome Atlas Project were included in the analysis, of which 64 were SRCC. Data extraction included patient demographics, blood types and risk factors, including clinical variables and genomics (either a 19-gene panel NGS or 1021-gene panel NGS). Univariate analyses were performed to identify factors significantly associated with overall survival. Results: The blood groups of 27 (42.2 %), 18 (28.1 %), 12 (18.8 %), and seven (10.9 %) patients were classified as O, A, B, and AB, respectively. We found that O was a unique blood group characterized by a low frequency of KRAS mutations, a high frequency of heterozygosity at each HLA class I locus, and a high tumor mutational burden (TMB). Patients in blood group A with high-frequency KRAS mutations and those in blood group B with anemia and metabolic abnormalities required targeted treatment. Furthermore, genetic alterations in SRCC differed from those in adenocarcinoma and mucinous adenocarcinoma. Conclusions: Our study revealed genomic changes in SRCC patients across different blood groups, which could advance the understanding and precise treatment of colorectal SRCC.

3.
Medicine (Baltimore) ; 103(31): e39193, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39093789

ABSTRACT

RATIONALE: At present, there is still insufficient understanding of the progression from persistent allergic reactions to severe reactions. Adrenaline remains the preferred medication for severe allergic reactions, and intramuscular injection of adrenaline can also be considered for patients with grade I reactions that are difficult to alleviate gastrointestinal symptoms. It is worth further discussing whether it is possible to break the conventional intramuscular injection recommended by the guidelines when the effect of intramuscular injection is not ideal for persistent grade I severe allergic reactions. PATIENT CONCERNS: A young male, 20 years of age, was admitted to emergency department because of repeated rash for 3 days and abdominal pain for 6 hours after taking traditional Chinese medicine. After hormone therapy, the rash continued to recur and secondary gastrointestinal symptoms occurred on the 3th day. Adrenaline intramuscular injection was given to temporarily relieve the rash and abdominal pain, but symptoms still persisted. DIAGNOSIS: The patient was diagnosed with persistent severe allergic reaction (grade I). INTERVENTIONS: Continuous intravenous infusion of low-dose adrenaline under electrocardiographic monitoring, real-time monitoring of heart rate and blood pressure, and routine treatment with methylprednisolone, diphenhydramine, calcium gluconate, and cetirizine. During this period, adrenaline intramuscular injection is temporarily added when abdominal pain symptoms are obvious. The entire treatment process used a total of 6.8 mg of adrenaline. OUTCOMES: During the entire period of adrenaline intervention, the patient did not experience any new discomfort, and there were no abnormal fluctuations in heart rate, rhythm, or blood pressure. The symptoms of rash and abdominal pain gradually improved. LESSONS: For patients with persistent grade I severe allergic reactions, intravenous administration of low-dose adrenaline under close vital sign monitoring is safe, feasible, and highly effective in preventing biphasic, persistent, or worsening allergic reactions.


Subject(s)
Epinephrine , Humans , Male , Epinephrine/administration & dosage , Young Adult , Injections, Intramuscular , Infusions, Intravenous , Abdominal Pain/drug therapy , Abdominal Pain/etiology , Drug Hypersensitivity/etiology , Drug Hypersensitivity/drug therapy , Drug Hypersensitivity/diagnosis , Severity of Illness Index
4.
Medicine (Baltimore) ; 103(31): e39194, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39093790

ABSTRACT

RATIONALE: Splenic abscess is relatively rare in clinical practice as an invasive disease. However, during the continuous prevalence of coronavirus disease 2019 (COVID-19), the incidence rate of splenic abscess showed an upward trend. However, because the etiology of splenic abscess is not specific, it is easy to be covered by the respiratory symptoms of COVID-19, resulting in omission or delay in diagnosis. If splenic abscesses cannot be treated in a timely manner, the mortality rate can reach 100%. Therefore, it is important to fully understand the correlation between COVID-19 and the development of splenic abscesses. PATIENT CONCERNS: A female patient, 71 years of age, was admitted to our hospital because of cough and sputum for 1 week and fever for 2 days. According to the positive results of novel coronavirus nucleic acid and chest computed tomography, novel coronavirus pneumonia was diagnosed. On the 4th day after treatment, abdominal distension and vomiting were observed. Abdominal ultrasound indicated splenomegaly and mixed echo masses in the spleen and abdominal computed tomography indicated 2 new round low-density lesions were found in the spleen. DIAGNOSES: The patient was diagnosed with secondary splenic abscess after COVID-19 infection. INTERVENTIONS: The patient and her family members refused to undergo ultrasound-guided splenic puncture drainage and splenectomy. In terms of treatment, she was given meropenem combined with vancomycin to continue anti-infection treatment. OUTCOMES: The patient's body temperature and infection indicators gradually increased, and the scope of splenic abscess continued to expand. The infection worsened and progressed to septic shock. The patient abandoned rescue drugs and invasive treatment, and died on the 9th day after admission. LESSONS: This case introduces the clinical characteristics of secondary splenic abscess caused by COVID-19 from the aspects of etiology, disease course, clinical manifestations, auxiliary examinations, and treatment methods. The focus is on improving the understanding of clinical doctors about secondary splenic abscesses caused by COVID-19, providing reference for early diagnosis and timely treatment.


Subject(s)
COVID-19 , SARS-CoV-2 , Splenic Diseases , Humans , COVID-19/complications , COVID-19/diagnosis , Female , Splenic Diseases/etiology , Aged , Abscess/etiology , Meropenem/therapeutic use , Tomography, X-Ray Computed
5.
Nat Commun ; 15(1): 6528, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095351

ABSTRACT

Cutting edge advances in electrical visual cortical prosthetics have evoked perception of shapes, motion, and letters in the blind. Here, we present an alternative optical approach using pulsed infrared neural stimulation. To interface with dense arrays of cortical columns with submillimeter spatial precision, both linear array and 100-fiber bundle array optical fiber interfaces were devised. We deliver infrared stimulation through these arrays in anesthetized cat visual cortex and monitor effects by optical imaging in contralateral visual cortex. Infrared neural stimulation modulation of response to ongoing visual oriented gratings produce enhanced responses in orientation-matched domains and suppressed responses in non-matched domains, consistent with a known higher order integration mediated by callosal inputs. Controls include dynamically applied speeds, directions and patterns of multipoint stimulation. This provides groundwork for a distinct type of prosthetic targeted to maps of visual cortical columns.


Subject(s)
Infrared Rays , Visual Cortex , Animals , Cats , Visual Cortex/physiology , Photic Stimulation/methods , Optical Fibers , Visual Prosthesis
6.
Int J Hyperthermia ; 41(1): 2386098, 2024.
Article in English | MEDLINE | ID: mdl-39097988

ABSTRACT

OBJECTIVE: To develop a novel scoring system based on magnetic resonance imaging (MRI) for predicting the difficulty of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids. MATERIALS AND METHODS: A total of 637 patients with uterine fibroids were enrolled. Sonication time, non-perfused volume ratio (NPVR), and ultrasound energy delivered for ablating 1 mm3 of fibroid tissue volume (E/V) were each classified as three levels and assigned scores from 0 to 2, respectively. Treatment difficulty level was then assessed by adding up the scores of sonication time, NPVR and E/V for each patient. The patients with score lower than 3 were categorized into low difficulty group, with score equal to or greater than 3 were categorized into high difficulty group. The potential predictors for treatment difficulty were compared between the two groups. Multifactorial logistic regression analysis model was created by analyzing the variables. The difficulty score system was developed using the beta coefficients of the logistic model. RESULTS: Signal intensity on T2WI, fibroid location index, largest diameter of fibroids, abdominal wall thickness, homogeneity of the signal of fibroids, and uterine position were independent influencing factors for the difficulty of USgHIFU for uterine fibroids. A prediction equation was obtained: difficulty score = 17 × uterine position (anteverted =0, retroverted =1)+71 × signal intensity (hypointense = 0, isointense/hyperintense = 1) +8 × enhancement (homogenous = 0, heterogeneous = 1)+25×(largest diameter of fibroids-20) +35 × (fibroid location index -0.2) +1×(abdominal wall thickness -5). CONCLUSIONS: This scoring system established based on MRI findings can be used to reliably predict the difficulty level of USgHIFU treatment of uterine fibroids.


Subject(s)
High-Intensity Focused Ultrasound Ablation , Leiomyoma , Magnetic Resonance Imaging , Humans , Female , Leiomyoma/diagnostic imaging , Leiomyoma/surgery , Leiomyoma/therapy , Leiomyoma/pathology , High-Intensity Focused Ultrasound Ablation/methods , Magnetic Resonance Imaging/methods , Adult , Middle Aged , Uterine Neoplasms/diagnostic imaging , Uterine Neoplasms/surgery , Uterine Neoplasms/therapy , Uterine Neoplasms/pathology
7.
Nat Commun ; 15(1): 7024, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39147746

ABSTRACT

To achieve high power conversion efficiency in perovskite/silicon tandem solar cells, it is necessary to develop a promising wide-bandgap perovskite absorber and processing techniques in relevance. To date, the performance of devices based on wide-bandgap perovskite is still limited mainly by carrier recombination at their electron extraction interface. Here, we demonstrate assembling a binary two-dimensional perovskite by both alternating-cation-interlayer phase and Ruddlesden-Popper phase to passivate perovskite/C60 interface. The binary two-dimensional strategy takes effects not only at the interface but also in the bulk, which enables efficient charge transport in a wide-bandgap perovskite solar cell with a stabilized efficiency of 20.79% (1 cm2). Based on this absorber, a monolithic perovskite/silicon tandem solar cell is fabricated with a steady-state efficiency of 30.65% assessed by a third party. Moreover, the tandem devices retain 96% of their initial efficiency after 527 h of operation under full spectral continuous illumination, and 98% after 1000 h of damp-heat testing (85 °C with 85% relative humidity).

8.
J Pharm Biomed Anal ; 250: 116405, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39151298

ABSTRACT

Therapeutic drug monitoring (TDM) of imatinib (IM) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. There was a significant correlation between unbound concentration and clinical response and toxicity, compared with total plasma concentrations, and the quantification of unbound IM and its metabolite, N-desmethyl imatinib (NDI) are of interest for TDM. However, traditional unbound drug separation methods have shortcomings, especially are susceptible to non-specific binding (NSB) of drugs to the polymer-constructed components of filter membranes, which are difficult to avoid at present. Hence it is necessary to developed a reliable separation method for the analysis of the unbound fraction of IM and NDI in TDM. We developed and validated an hollow fiber solid phase microextraction (HF-SPME) method coupled with high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) that to measure unbound IM and NDI concentration in human plasma. It used the NSB phenomenon and solve the NSB problem. The preparation procedure only involves a common vortex and ultrasonication without dilution of samples and modification of membrane. A total of 50 chronic myeloid leukemia (CML) patients were enrolled in our study. The relationship between the unbound and total concentrations for IM and NDI, as well as the concentration ratios of NDI to IM in 50 clinical plasma samples were investigated. The extraction recovery is high to 95.5-106 % with validation parameters for the methodological results were all excellent. There were both a poor linear relationship between the unbound and total concentrations for IM (r2=0.504) and NDI (r2=0.201) in 50 clinical plasma samples. The unbound concentration ratios of NDI to IM varied widely in CML patients. The determination of unbound IM and NDI concentration is meaningful and necessary. The developed HF-SPME method is simple, accurate and precise that could be used to measure unbound IM and NDI concentration in clinical TDM.

9.
Anal Chem ; 96(33): 13438-13446, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39129352

ABSTRACT

Pyroptosis of programmed cell death has been recognized as a more effective way to inhibit the occurrence and development of tumors than the better-studied apoptosis. However, it is still challenging to quickly and effectively trigger pyroptosis of cancer cells for high-efficacy cancer treatment. Here, we report on the first use of mild constant-potential electrostimulation (cp-ES) to quickly trigger cancer cell pyroptosis with a probability up to ∼91.4% and significantly shortened time (within 1 h), ∼3-6 times faster than typical drug stimulation to induce pyroptosis. We find that the ES-induced cancer cell pyroptosis is through the activated caspase-3 (pathway) cleavage of gasdermin E (GSDME) to form an N-terminal fragment (GSDME-N) and observe nuclear shrinkage and reduction of the number of nucleoli as well as down-/up-regulated expression of two important nucleoproteins of nucleolin and nucleophosmin (NPM1). The study enriches the basic understanding of pyroptosis and provides a new avenue for potential effective treatment of cancer.


Subject(s)
Caspase 3 , Nucleophosmin , Pyroptosis , Humans , Caspase 3/metabolism , Nucleolin , Cell Line, Tumor , Cell Nucleus/metabolism , Nuclear Proteins/metabolism , Phosphate-Binding Proteins/metabolism , RNA-Binding Proteins/metabolism , Gasdermins
10.
Rev Med Virol ; 34(5): e2575, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39160646

ABSTRACT

Neurotropic viral infections pose a significant challenge due to their ability to target the central nervous system and cause severe neurological complications. Traditional antiviral therapies face limitations in effectively treating these infections, primarily due to the blood-brain barrier, which restricts the delivery of therapeutic agents to the central nervous system. Nanoparticle-based therapies have emerged as a promising approach to overcome these challenges. Nanoparticles offer unique properties that facilitate drug delivery across biological barriers, such as the blood-brain barrier, and can be engineered to possess antiviral activities.


Subject(s)
Antiviral Agents , Blood-Brain Barrier , Central Nervous System Viral Diseases , Nanoparticles , Humans , Nanoparticles/chemistry , Antiviral Agents/therapeutic use , Antiviral Agents/pharmacology , Animals , Blood-Brain Barrier/drug effects , Central Nervous System Viral Diseases/drug therapy , Central Nervous System Viral Diseases/virology , Drug Delivery Systems , Virus Diseases/drug therapy , Virus Diseases/virology
11.
Microbiol Spectr ; : e0089624, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39162533

ABSTRACT

With the widespread misuse of disinfectants, the clinical susceptibility of Klebsiella pneumoniae (K. pneumoniae) to chlorhexidine (CHX) has gradually diminished, posing significant challenges to clinical disinfection and infection control. K. pneumoniae employs overexpression of efflux pumps and the formation of thick biofilms to evade the lethal effects of CHX. Plumbagin (PLU) is a natural plant extract that enhances membrane permeability and reduces proton motive force. In this study, we elucidated the synergistic antimicrobial activity of PLU in combination with CHX, effectively reducing the MIC of CHX against K. pneumoniae to 1 µg/mL and below. Crucially, through crystal violet staining and confocal laser scanning microscopy live/dead staining, we discovered that PLU significantly enhances the anti-biofilm capability of CHX. Mechanistically, experiments involving membrane permeability, alkaline phosphatase leakage, reactive oxygen species, and RT-qPCR suggest that the combination of PLU and CHX improves the permeability of bacterial inner and outer membranes, promotes bacterial oxidative stress, and inhibits oqxA/B efflux pump expression. Furthermore, we conducted surface disinfection experiments on medical instruments to simulate clinical environments, demonstrating that the combination effectively reduces bacterial loads by more than 3 log10 CFU/mL. Additionally, results from resistance mutation frequency experiments indicate that combined treatment reduces the generation of resistant mutants within the bacterial population. In summary, PLU can serve as an adjuvant, enhancing the anti-biofilm capability of CHX and reducing the occurrence of resistance mutations, thereby extending the lifespan of CHX.IMPORTANCEAs disinfectants are extensively and excessively utilized worldwide, clinical pathogens are progressively acquiring resistance against these substances. However, high concentrations of disinfectants can lead to cross-resistance to antibiotics, and concurrent use of different disinfectants can promote bacterial resistance mutations and facilitate the horizontal transfer of resistance genes, which poses significant challenges for clinical treatment. Compared with the lengthy process of developing new disinfectants, enhancing the effectiveness of existing disinfectants with natural plant extracts is important and meaningful. CHX is particularly common and widely used compared with other disinfectants. Meanwhile, Klebsiella pneumoniae, as a clinically significant pathogen, exhibits high rates of resistance and pathogenicity. Previous studies and our data indicate a significant decrease in the sensitivity of clinical K. pneumoniae to CHX, highlighting the urgent need for novel strategies to address this issue. In light of this, our research is meaningful.

12.
Clin Ther ; 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39155175

ABSTRACT

PURPOSE: This study aimed to evaluate the cost-effectiveness of Azvudine for the treatment of mild-to-moderate coronavirus disease 2019 in high-risk outpatients using real-world data and relevant references. METHODS: In the decision-tree model, 2 cohorts were organized in a single center to compare the cost-effectiveness between the Azvudine plus symptomatic treatment group and the symptomatic treatment group. We calculated the cost and mortality rate for both groups. The incremental cost-effectiveness ratio was used to illustrate the cost-effectiveness. To assess the uncertainty of the model parameters, we conducted 1-way and probabilistic sensitivity analyses. FINDINGS: In total, there were 804 outpatients included in the model. Among these, 317 patients received Azvudine plus symptomatic treatment, whereas the remaining 487 participants were treated with symptomatic treatment alone. The costs in the Azvudine and control groups were 1055.48 yuan and 2466.97 yuan and the survival rates were 100.00% and 98.70%, respectively. After calculation, the incremental cost-effectiveness ratio was determined to be -108,817.48 yuan per person. In the section of 1-way and probabilistic sensitivity analyses, Azvudine was still proven to be cost-effective. IMPLICATIONS: Our results support the usage of Azvudine for the treatment of high-risk outpatients with mild-to-moderate coronavirus disease 2019 from economic perspective.

13.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(4): 361-366, 2024 Jul 30.
Article in Chinese | MEDLINE | ID: mdl-39155246

ABSTRACT

This study aims at developing a dataset for determining the presence of carotid artery plaques in ultrasound images, composed of 1761 ultrasound images from 1165 participants. A deep learning architecture that combines bilinear convolutional neural networks with residual neural networks, known as the single-input BCNN-ResNet model, was utilized to aid clinical doctors in diagnosing plaques using carotid ultrasound images. Following training, internal validation, and external validation, the model yielded an ROC AUC of 0.99 (95% confidence interval: 0.91 to 0.84) in internal validation and 0.95 (95% confidence interval: 0.96 to 0.94) in external validation, surpassing the ResNet-34 network model, which achieved an AUC of 0.98 (95% confidence interval: 0.99 to 0.95) in internal validation and 0.94 (95% confidence interval: 0.95 to 0.92) in external validation. Consequently, the single-input BCNN-ResNet network model has shown remarkable diagnostic capabilities and offers an innovative solution for the automatic detection of carotid artery plaques.


Subject(s)
Artificial Intelligence , Carotid Arteries , Deep Learning , Neural Networks, Computer , Humans , Carotid Arteries/diagnostic imaging , Ultrasonography , Plaque, Atherosclerotic/diagnostic imaging , Carotid Stenosis/diagnostic imaging , Image Processing, Computer-Assisted/methods , Carotid Artery Diseases/diagnostic imaging
14.
Eur J Pharm Sci ; 201: 106876, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39128815

ABSTRACT

BACKGROUND: Valproic acid (VPA) is a commonly used broad-spectrum antiepileptic drug. For elderly epileptic patients, VPA plasma concentrations have a considerable variation. We aim to establish a prediction model via a combination of machine learning and population pharmacokinetics (PPK) for VPA plasma concentration. METHODS: A retrospective study was performed incorporating 43 variables, including PPK parameters. Recursive Feature Elimination with Cross-Validation was used for feature selection. Multiple algorithms were employed for ensemble model, and the model was interpreted by Shapley Additive exPlanations. RESULTS: The inclusion of PPK parameters significantly enhances the performance of individual algorithm model. The composition of categorical boosting, light gradient boosting machine, and random forest (7:2:1) with the highest R2 (0.74) was determined as the ensemble model. The model included 11 variables after feature selection, of which the predictive performance was comparable to the model that incorporated all variables. CONCLUSIONS: Our model was specifically tailored for elderly epileptic patients, providing an efficient and cost-effective approach to predict VPA plasma concentration. The model combined classical PPK with machine learning, and underwent optimization through feature selection and algorithm integration. Our model can serve as a fundamental tool for clinicians in determining VPA plasma concentration and individualized dosing regimens accordingly.

15.
Clin Appl Thromb Hemost ; 30: 10760296241268421, 2024.
Article in English | MEDLINE | ID: mdl-39149981

ABSTRACT

INTRODUCTION AND OBJECTIVES: The present study aimed to investigate different peripheral lymphocyte subsets in patients with severe hemophilia A (HA) and factor VIII (FVIII) inhibitor production. For this, age-matched cases of 19 FVIII inhibitor-positive (IP), 21 FVIII inhibitor-negative (IN) and 45 healthy controls were selected for study. METHODS: Flow cytometry was used to analyze the peripheral lymphocyte subsets, including T, B, natural killer (NK) and NKT cells. The T cell subsets included CD3 + CD4-CD8- [double negative T (DNT)], CD3 + CD4 + CD8+ [double-positive T (DPT)], CD3 + CD4 + CD8- and CD3 + CD4-CD8+ T cells. Pairwise comparisons of absolute lymphocyte subset values were conducted among the three groups. The cut-off value for absolute lymphocyte counts was determined using receiver operating characteristic curve analysis. RESULTS: The results demonstrated that the absolute values of DPT cells in the IN and IP groups were significantly lower than those in the healthy control group (P = 0.007). The DNT values were also lower in severe HA patients with or without inhibitor than those in healthy subjects, but these differences were not statistically significant (P = 0.053). In addition, the absolute value of CD4+ Th cells in the IP group was lower than that in the healthy controls (P = 0.013). Although not statistically significant (P = 0.064), the absolute values of NKT cells were higher in the IN group compared with the IP group, and higher in the IP group compared with the healthy control group. There were no statistically significant differences in total T, B, CD8 + and NK cells among the IN, IP and healthy control groups. The cut-off value for absolute CD4+ Th cells in the IN group was < 598/µl. CONCLUSION: The decrease in absolute values of CD4+ Th cells in severe HA patients may contribute to the establishment of infused FVIII immune tolerance. If the CD4+ Th value remains > 598/µl, clinicians should be vigilant for possible FVIII inhibitor production, especially on days prior to FVIII exposure.


Subject(s)
Factor VIII , Hemophilia A , Lymphocyte Subsets , Humans , Hemophilia A/blood , Hemophilia A/immunology , Case-Control Studies , Factor VIII/immunology , Male , Adult , Adolescent , Young Adult , Female , Child
18.
Front Mol Biosci ; 11: 1421597, 2024.
Article in English | MEDLINE | ID: mdl-39119475

ABSTRACT

Background: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a syn-drome with a high short-term mortality rate, and its prognosis is critical in clinical management. This study aimed to investigate the clinical significance of glutathione peroxidase 4 (GPX4) in the occurrence and development of HBV-ACLF and its prognostic value for 90-day mortality. Methods: The expression levels of GPX4, oxidative stress-related molecules and inflammatory cytokines in serum or peripheral blood mononuclear cells (PBMCs) of 289 participants were determined by RT-qPCR or ELISA, and the methylation level of GPX4 promoter in PBMCs was determined by MethyLight. Results: The expression levels of GPX4 in the PBMCs and serum of HBV-ACLF patients were lower than those in non-HBV-associated acute-on-chronic liver failure (non-HBV ACLF) patients, patients with chronic hepatitis B (CHB) and healthy control (HC) individuals, while the methylation level of the GPX4 promoter was greater. In HBV-ACLF patients, the methylation level of the GPX4 promoter is correlated with oxidative stress, inflammation-related molecules, and some clinicopathological indicators. The methylation level of the GPX4 promoter was identified as an independent risk factor for 90-day mortality in HBV-ACLF patients and yielded a larger area under the receiver operating characteristic curve (AUROC) than the model for end-stage liver disease (MELD) score in predicting 90-day mortality. Conclusion: The GPX4 promoter methylation level has promising potential as a predictor of 90-day mortality in patients with HBV-ACLF.

19.
J Plant Res ; 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39112806

ABSTRACT

The vascular bundle in the ear-internode of maize is a key conduit for transporting photosynthetic materials between "source" and "sink", making it critically important to examine its micro-phenotypes and genetic architecture to identify advantageous characteristics and cultivate high-yielding and high-quality varieties. Unfortunately, the limited observation methods and scope of study precludes any comprehensive and systematic investigations into the microscopic phenotypes and genetic mechanisms of vascular bundle in maize ear-internode. In this study, 47 phenotypic traits were extracted in 495 maize inbred lines using micro computed tomography (Micro-CT) scanning technology and a deep learning-based phenotype acquisition method for stem vascular bundle, which included stem slice-related, epidermis zone-related, periphery zone-related, inner zone-related and vascular bundles-related traits. Phenotypic analysis indicated that there was extensive phenotypic variation of vascular bundle traits in ear-internode, especially that in the inner zone. Of these, 30 phenotypic traits with heritability greater than 0.70 were conducted for GWAS, and a total of 4,225 significant SNPs and 416 candidate genes with detailed functional annotations were identified. Furthermore, 20 genes were highly expressed in stem-related tissues, especially in maize internodes. Functional analysis of candidate genes indicated that the pathways obtained for candidate genes of different trait groups were distinct, mainly involved in vitamin synthesis and metabolism, transport of substances, carbohydrate derivative catabolic process, protein transport and localization, and anatomical structure development. The results of this study will help to further understand the phenotypic traits of stem vascular bundles and provide a reference for revealing the genetic mechanism of maize ear-internode vascular bundles.

20.
Sci Rep ; 14(1): 18782, 2024 08 13.
Article in English | MEDLINE | ID: mdl-39138327

ABSTRACT

Infections caused by pathogenic Escherichia coli are a serious threat to human health, while conventional antibiotic susceptibility tests (AST) have a long turn-around time, and rapid antibiotic susceptibility methods are urgently needed to save lives in the clinic, reduce antibiotic misuse and prevent emergence of antibiotic-resistant bacteria. We optimized and validated the feasibility of a novel rapid AST based on SYBR Green I and Propidium Iodide (SGPI-AST) for E. coli drug susceptibility test. A total of 112 clinical isolates of E. coli were collected and four antibiotics (ceftriaxone, cefoxitin, imipenem, meropenem) were selected for testing. Bacterial survival rate of E. coli was remarkably linearly correlated with S value at different OD600 values. After optimizing the antibiotic concentrations, the sensitivity and specificity of SGPI-AST reached 100%/100%, 97.8%/100%, 100%/100% and 98.4%/99% for ceftriaxone, cefoxitin, imipenem and meropenem, respectively, and the corresponding concordances of the SGPI-AST with conventional AST were 1.000, 0.980, 1.000 and 0.979, respectively. The SGPI-AST can rapidly and accurately determine the susceptibility of E. coli clinical isolates to multiple antibiotics in 60 min, and has the potential to be applied to guide the precise selection of antibiotics for clinical management of infections caused by pathogenic E. coli.


Subject(s)
Anti-Bacterial Agents , Benzothiazoles , Diamines , Escherichia coli , Microbial Sensitivity Tests , Organic Chemicals , Propidium , Quinolines , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Microbial Sensitivity Tests/methods , Benzothiazoles/pharmacology , Anti-Bacterial Agents/pharmacology , Humans , Quinolines/pharmacology , Organic Chemicals/pharmacology , Diamines/pharmacology , Propidium/analogs & derivatives , Propidium/pharmacology , Escherichia coli Infections/microbiology , Escherichia coli Infections/drug therapy
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