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1.
Sci Rep ; 14(1): 10776, 2024 05 11.
Article En | MEDLINE | ID: mdl-38734750

The age, creatinine, and ejection fraction (ACEF) score has been accepted as a predictor of poor outcome in elective operations. This study aimed to investigate the predictive value of ACEF score in acute type A aortic dissection (AAAD) patients after total arch replacement. A total of 227 AAAD patients from July 2021 and June 2022 were enrolled and divided into Tertiles 1 (ACEF ≤ 0.73), Tertiles 2 (0.73 < ACEF ≤ 0.95), and Tertiles 3 (ACEF > 0.95). Using inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Cox logistic regression was used to further evaluate the survival prediction ability of ACEF score. The in-hospital mortality was 9.8%. After IPTW, in the baseline characteristics reached an equilibrium, a higher ACEF score before operation still associated with higher in-hospital mortality. After 1 year follow-up, 184 patients (90.6%) survival. Multivariable analysis revealed that ACEF score (adjusted hazard ratio 1.68; 95% confidence interval 1.34-4.91; p = 0.036) and binary ACEF score (adjusted HR 2.26; 95% CI 1.82-6.20; p < 0.001) was independently associated with 1-year survival. In addition, net reclassification improvement (NRI) and integrated differentiation improvement (IDI) verified that the ACEF score and binary ACEF score is an accurate predictive tool in clinical settings. In conclusions, ACEF score could be considered as a useful tool to risk stratification in patients with AAAD before operation in daily clinical work.


Aortic Dissection , Creatinine , Hospital Mortality , Humans , Female , Male , Aortic Dissection/surgery , Aortic Dissection/mortality , Middle Aged , Creatinine/blood , Aged , Stroke Volume , Age Factors , Prognosis , Predictive Value of Tests , Aorta, Thoracic/surgery , Retrospective Studies , Aortic Aneurysm, Thoracic/surgery , Aortic Aneurysm, Thoracic/mortality
2.
Int J Gen Med ; 17: 1937-1948, 2024.
Article En | MEDLINE | ID: mdl-38736673

Purpose: This study was aimed at exploring the use of the acute gastrointestinal injury (AGI) grade and sensitive biomarkers to investigate gastrointestinal (GI) injury in early stage of acute pancreatitis (AP). Patients and Methods: The AGI grade was used to evaluate intestinal function. Any GI injury above grade I (grades II-IV) was considered as severe. An AP rat model was created by retrograde injection of 4% sodium taurocholate. The pancreatic and intestinal histopathology scores were calculated by hematoxylin-eosin staining. Human and rat sera were assessed using ELISA. Tight junction (TJ) proteins were detected by Western blotting. Results: In clinical study, the GI injury rate in mild acute pancreatitis (MAP), moderate severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP) groups was 26.8%, 78.4%, and 94.8%, respectively (P < 0.05). Diamine oxidase (DAO), histidine decarboxylase (HDC), and matrix metalloproteinase 8 (MMP8) serum levels were higher in AP patients than in healthy people (P < 0.05). Patients with GI injury had higher serum levels of DAO, HDC, and MMP8 than those without GI injury (P < 0.05). In animal experiments, the serum levels of DAO, HDC, and MMP8 were higher in the AP group than in normal and sham-operated (SO) groups (P < 0.05). The expressions of tricellulin, claudin-1, ZO-1, and occludin were significantly lower in the AP group than in normal and SO groups (P < 0.05). Conclusion: The serum levels of DAO, HDC, and MMP8 are novel biomarkers of GI injury in the early stage of AP; their elevation indicates the development of GI injury in AP. The intestinal TJ disruption may be a primary mechanism of GI injury and requires more in-depth research.

3.
BMC Genomics ; 25(1): 460, 2024 May 11.
Article En | MEDLINE | ID: mdl-38730330

BACKGROUND: Zingiber officinale Roscoe, colloquially known as ginger, is a crop of significant medicinal and culinary value that frequently encounters adversity stemming from inhospitable environmental conditions. The MYB transcription factors have garnered recognition for their pivotal role in orchestrating a multitude of plant biological pathways. Nevertheless, the enumeration and characterization of the MYBs within Z. officinale Roscoe remains unknown. This study embarks on a genome-wide scrutiny of the MYB gene lineage in ginger, with the aim of cataloging all ZoMYB genes implicated in the biosynthesis of gingerols and curcuminoids, and elucidating their potential regulatory mechanisms in counteracting abiotic stress, thereby influencing ginger growth and development. RESULTS: In this study, we identified an MYB gene family comprising 231 members in ginger genome. This ensemble comprises 74 singular-repeat MYBs (1R-MYB), 156 double-repeat MYBs (R2R3-MYB), and a solitary triple-repeat MYB (R1R2R3-MYB). Moreover, a comprehensive analysis encompassing the sequence features, conserved protein motifs, phylogenetic relationships, chromosome location, and gene duplication events of the ZoMYBs was conducted. We classified ZoMYBs into 37 groups, congruent with the number of conserved domains and gene structure analysis. Additionally, the expression profiles of ZoMYBs during development and under various stresses, including ABA, cold, drought, heat, and salt, were investigated in ginger utilizing both RNA-seq data and qRT-PCR analysis. CONCLUSION: This work provides a comprehensive understanding of the MYB family in ginger and lays the foundation for the future investigation of the potential functions of ZoMYB genes in ginger growth, development and abiotic stress tolerance of ginger.


Multigene Family , Phylogeny , Plant Proteins , Stress, Physiological , Transcription Factors , Zingiber officinale , Zingiber officinale/genetics , Stress, Physiological/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant
4.
Cell Rep ; 43(5): 114237, 2024 May 15.
Article En | MEDLINE | ID: mdl-38753484

Cardiac dysfunction, an early complication of endotoxemia, is the major cause of death in intensive care units. No specific therapy is available at present for this cardiac dysfunction. Here, we show that the N-terminal gasdermin D (GSDMD-N) initiates mitochondrial apoptotic pore and cardiac dysfunction by directly interacting with cardiolipin oxidized by complex II-generated reactive oxygen species (ROS) during endotoxemia. Caspase-4/11 initiates GSDMD-N pores that are subsequently amplified by the upregulation and activation of NLRP3 inflammation through further generation of ROS. GSDMD-N pores form prior to BAX and VDAC1 apoptotic pores and further incorporate into BAX and VDAC1 oligomers within mitochondria membranes to exacerbate the apoptotic process. Our findings identify oxidized cardiolipin as the definitive target of GSDMD-N in mitochondria of cardiomyocytes during endotoxin-induced myocardial dysfunction (EIMD), and modulation of cardiolipin oxidation could be a therapeutic target early in the disease process to prevent EIMD.

5.
Trials ; 25(1): 328, 2024 May 18.
Article En | MEDLINE | ID: mdl-38760804

BACKGROUND: The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses. METHODS: We will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The trial is named "SCARLET" (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the SpO2:FiO2 ratio on study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined. DISCUSSION: Citicoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients. TRIAL REGISTRATION: The trial was registered at www. CLINICALTRIALS: gov on 5/31/2023 (NCT05881135). TRIAL STATUS: Currently enrolling.


COVID-19 , Cytidine Diphosphate Choline , Randomized Controlled Trials as Topic , SARS-CoV-2 , Humans , Cytidine Diphosphate Choline/therapeutic use , Double-Blind Method , SARS-CoV-2/drug effects , COVID-19/complications , COVID-19 Drug Treatment , Clinical Trials, Phase II as Topic , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Pneumonia, Viral/complications , Treatment Outcome , Hypoxia/drug therapy , Male , Pandemics , Coronavirus Infections/drug therapy , Coronavirus Infections/complications , Hospitalization , Female , Betacoronavirus , Clinical Trials, Phase I as Topic , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Administration, Intravenous , Adult
6.
Osteoporos Int ; 2024 May 07.
Article En | MEDLINE | ID: mdl-38713246

The novel metaPGS, integrating multiple fracture-related genetic traits, surpasses traditional polygenic scores in predicting fracture risk. Demonstrating a robust association with incident fractures, this metaPGS offers significant potential for enhancing clinical fracture risk assessment and tailoring prevention strategies. INTRODUCTION: Current polygenic scores (PGS) have limited predictive power for fracture risk. To improve genetic prediction, we developed and evaluated a novel metaPGS combining genetic information from multiple fracture-related traits. METHODS: We derived individual PGS from genome-wide association studies of 16 fracture-related traits and employed an elastic-net logistic regression model to examine the association between the 16 PGSs and fractures. An optimal metaPGS was constructed by combining 11 significant individual PGSs selected by the elastic regularized regression model. We evaluated the predictive power of the metaPGS alone and in combination with clinical risk factors recommended by guidelines. The discrimination ability of metaPGS was assessed using the concordance index. Reclassification was assessed using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The metaPGS had a significant association with incident fractures (HR 1.21, 95% CI 1.18-1.25 per standard deviation of metaPGS), which was stronger than previously developed bone mineral density (BMD)-related individual PGSs. Models with PGS_FNBMD, PGS_TBBMD, and metaPGS had slightly higher but statistically non-significant c-index than the base model (0.640, 0.644, 0.644 vs. 0.638). However, the reclassification analysis showed that compared to the base model, the model with metaPGS improves the reclassification of fracture. CONCLUSIONS: The metaPGS is a promising approach for stratifying fracture risk in the European population, improving fracture risk prediction by combining genetic information from multiple fracture-related traits.

7.
Cell Host Microbe ; 2024 May 13.
Article En | MEDLINE | ID: mdl-38754418

The gut microbiota is closely linked to atherosclerosis. However, the role of intestinal fungi, essential members of the complex microbial community, in atherosclerosis is poorly understood. Herein, we show that gut fungi dysbiosis is implicated in patients with dyslipidemia, characterized by higher levels of Candida albicans (C. albicans), which are positively correlated with plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels. Furthermore, C. albicans colonization aggravates atherosclerosis progression in a mouse model of the disease. Through gain- and loss-of-function studies, we show that an intestinal hypoxia-inducible factor 2α (HIF-2α)-ceramide pathway mediates the effect of C. albicans. Mechanistically, formyl-methionine, a metabolite of C. albicans, activates intestinal HIF-2α signaling, which drives increased ceramide synthesis to accelerate atherosclerosis. Administration of the HIF-2α selective antagonist PT2385 alleviates atherosclerosis in mice by reducing ceramide levels. Our findings identify a role for intestinal fungi in atherosclerosis progression and highlight the intestinal HIF-2α-ceramide pathway as a target for atherosclerosis treatment.

8.
Int J Cardiol ; : 132182, 2024 May 14.
Article En | MEDLINE | ID: mdl-38754583

BACKGROUND: This study aimed to assess the early- and mid-term outcomes of aortic root repair and replacement, and to provide evidence to improve root management in acute type A aortic dissection (AAAD). METHODS: This study enrolled 455 patients who underwent AAAD root repair (n = 307) or replacement (n = 148) between January 2016 and December 2017. Inverse probability of treatment weighting (IPTW) method was used to control for treatment selection bias. The primary outcomes were in-hospital mortality, mid-term survival, and proximal aortic reintervention. RESULTS: The success rate of root repair was 99.7%. The in-hospital mortality in the conservative root repair (CRR) and aggressive root replacement (ARR) were 8.1% and 10.8%. The median follow-up time was 67.76 months (IQR, 67-72 months). After adjusting for baseline factors, there was no significant differences in mid-term survival (p = .750) or the proximal aortic reintervention rate (p = .550) between the two groups. According to Cox analysis, age, hypertension, severe aortic regurgitation, CPB time, and concomitant CABG were all factors associated with mid-term mortality. Regarding reintervention, multivariate analysis identified renal insufficiency, bicuspid aortic valve, root diameter ≥ 45 mm, and severe aortic regurgitation as risk factors, while CRR did not increase the risk of reintervention. The subgroup analysis revealed heterogeneity in the effects of surgical treatment across diverse populations based on a variety of risk factors. CONCLUSIONS: For patients with AAAD, both CRR and ARR are appropriate operations with promising early and mid-term outcomes. The effects of treatment show heterogeneity across diverse populations based on various risk factors.

9.
J Econ Entomol ; 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38603566

Whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is a destructive insect pest of many crops. Rickettsia infection in different cryptic species of B. tabaci has been observed worldwide. Understanding the interactions between these 2 organisms is critical to developing Rickettsia-based strategies to control B. tabaci and thereby reduce the transmission of related vector-borne viruses. In this study, we investigated the effects of Rickettsia infection on the biological characteristics of the Middle East Asia Minor 1 (MEAM1) strain of B. tabaci through biological analysis of infected and uninfected individuals. The results of this study suggest that Rickettsia may confer fitness benefits. These benefits include increased fertility, improved survival rates, accelerated development, and resulted in female bias. We also investigated the transcriptomics impact of Rickettsia infection on B. tabaci by performing a comparative RNA-seq analysis of nymphs and adult females, both with and without the infection. Our analysis revealed 218 significant differentially expressed genes (DEGs) in infected nymphs compared to uninfected ones and 748 significant DEGs in infected female adults compared to their uninfected whiteflies. Pathway analysis further revealed that Rickettsia can affect many important metabolic pathways in whiteflies. The results suggest that Rickettsia plays an essential role in energy metabolism, and nutrient synthesis in the B. tabaci MEAM1, and depends on metabolites obtained from the host to ensure its survival. Overall, our findings suggest that Rickettsia has beneficial effects on B. tabaci and offered insights into the potential molecular mechanisms governing the interactions between Rickettsia and B. tabaci MEAM1.

10.
Am J Cancer Res ; 14(3): 1204-1216, 2024.
Article En | MEDLINE | ID: mdl-38590401

Changes in protein ubiquitination have been linked to cancer. Deubiquitinating enzymes (DUBs) counteract E3 ligase activities and have emerged as promising targets for cancer treatment. Ubiquitin-specific peptidase 5 (USP5) is a member of the DUBs family and has been implicated in promoting tumorigenesis in numerous cancers. However, the clinical significance and biological function of USP5 in osteosarcoma (OS) remains unclear. Here, we found elevated USP5 expression in OS tissues compared with normal bone tissues. Furthermore, we observed significant associations of elevated USP5 levels with increased mortality and more malignant phenotypes in OS patients. Moreover, our results revealed that USP5 could facilitate metastasis and cell progression in OS by activating the hedgehog (Hh) signaling pathway using cultured cells and animal tumor models. Mechanistically, USP5 appeared to stabilize and deubiquitinate Gli1, a key mediator of the Hh signaling pathway. Additionally, the oncogenic effect of USP5 in OS was dependent on Gli1 stability. Our findings support the model where USP5 contributes to OS pathogenesis by activating the Hh/Gli1 signaling pathway, making USP5 a potential diagnostic and therapeutic target for OS.

11.
Enzyme Microb Technol ; 178: 110447, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38626534

Clostridium butyricum (C. butyricum) represents a new generation of probiotics, which is beneficial because of its good tolerance and ability to produce beneficial metabolites, such as short-chain fatty acids and enzymes; however, its low enzyme activity limits its probiotic efficacy. In this study, a mutant strain, C. butyricum FZM 240 was obtained using carbon ion beam irradiation, which exhibited greatly improved enzyme production and tolerance. The highest filter paper, endoglucanase, and amylase activities produced by C. butyricum FZM 240 were 125.69 U/mL, 225.82 U/ mL, and 252.28 U/mL, which were 2.58, 1.95, and 2.21-fold higher, respectively, than those of the original strain. The survival rate of the strain increased by 11.40 % and 5.60 % after incubation at 90 °C for 5 min and with simulated gastric fluid at pH 2.5 for 2 h, respectively, compared with that of the original strain. Whole-genome resequencing and quantitative real-time PCR(qRT-PCR) analysis showed that the expression of genes related to enzyme synthesis (GE000348, GE001963 and GE003123) and tolerance (GE001114) was significantly up-regulated, while that of genes related to acid metabolism (GE003450) was significantly down-regulated. On this basis, homology modeling and functional prediction of the proteins encoded by the mutated genes were performed. According to the results, the properties related to the efficacy of C. butyricum as a probiotic were significantly enhanced by carbon ion beam irradiation, which is a novel strategy for the application of Clostridium spp. as feed additives.

12.
Diagn Pathol ; 19(1): 58, 2024 Apr 14.
Article En | MEDLINE | ID: mdl-38616252

BACKGROUND: Crizotinib, an oral first-generation tyrosine kinase inhibitor (TKI), is superior to systemic chemotherapy for the treatment of non-small cell lung cancer (NSCLC) with positive rearrangement of anaplastic lymphoma kinase (ALK). However, an increased incidence of renal and hepatic cysts has been reported in the patients on crizotinib treatment. CASE PRESENTATION: Here, we describe a case of a 71-year-old Chinese women developed multiple cystic lesions in kidney and liver during crizotinib treatment for the primary and metastatic NSCLC. The renal and hepatic cysts were noted by CT scan 3 months after crizotinib treatment, which were spontaneously and significantly regressed after stopping crizotinib. CONCLUSIONS: Based on literature review and our experience in this case report, we concluded that crizotinib-associated renal cyst (CARCs) has features of malignancy and abscess in radiographic imaging, and thus, pathological confirmation is necessary to avoid inappropriate treatment decision. In addition, to benefit the patients with progress-free survival (PFS), switching from crizotinib to alectinib is recommended for the treatment of NSCLC patients who developed CARCs.


Carcinoma, Non-Small-Cell Lung , Cysts , Kidney Diseases, Cystic , Lung Neoplasms , Humans , Female , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Crizotinib/adverse effects , Anaplastic Lymphoma Kinase/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Kidney Diseases, Cystic/chemically induced , Kidney Diseases, Cystic/diagnosis , Kidney Diseases, Cystic/genetics , Cysts/chemically induced
13.
Diabetes Obes Metab ; 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38646838

AIM: To investigate the metabolism and disposition characteristics of HSK7653 in healthy male Chinese participants. METHODS: A single oral dose of 80 µCi (25 mg) [14C]HSK7653 capsules was administered to six healthy participants, and blood, plasma, urine and faeces were collected. Quantitative and qualitative analysis was conducted to investigate the pharmacokinetics, blood-to-plasma ratio, mass balance and metabolism of HSK7653. RESULTS: The drug was well absorbed and reached a maximum concentration at 1.25 h. The drug-related components (HSK7653 and its metabolites) were eliminated slowly, with a half-life (t1/2) of 111 h. Unchanged HSK7653 contributed to more than 97% of the total radioactivity in all plasma samples. The blood-to-plasma ratio (0.573-0.845) indicated that HSK7653 did not tend to distribute into blood cells. At 504 h postdose, up to 95.9% of the dose was excreted, including 79.8% in urine and 16.1% in faeces. Most of the radioactivity (75.5% dose) in excreta was unchanged HSK7653. In addition, nine metabolites were detected in urine and faeces. The most abundant metabolite was M6-2, a dioxidation product of HSK7653, which accounted for 4.73% and 2.63% of the dose in urine and faeces, respectively. The main metabolic pathways of HSK7653 in vivo included oxidation, pyrrole ring opening and sulphonamide hydrolysation. CONCLUSION: HSK7653 was well absorbed, slightly metabolized and slowly excreted in humans. The high plasma exposure and long t1/2 of HSK7653 may contribute to its long-lasting efficacy as a long-acting dipeptidyl peptidase-4 inhibitor.

14.
Front Pharmacol ; 15: 1309178, 2024.
Article En | MEDLINE | ID: mdl-38650631

Isorhamnetin (ISO) is a phenolic compound belonging to flavonoid family, showcasing important in vitro pharmacological activities such as antitumor, anti-inflammation, and organ protection. ISO is predominantly extracted from Hippophae rhamnoides L. This plant is well-known in China and abroad because of its "medicinal and food homologous" characteristics. As a noteworthy natural drug candidate, ISO has received considerable attention in recent years owing to its low cost, wide availability, high efficacy, low toxicity, and minimal side effects. To comprehensively elucidate the multiple biological functions of ISO, particularly its antitumor activities and other pharmacological potentials, a literature search was conducted using electronic databases including Web of Science, PubMed, Google Scholar, and Scopus. This review primarily focuses on ISO's ethnopharmacology. By synthesizing the advancements made in existing research, it is found that the general effects of ISO involve a series of in vitro potentials, such as antitumor, protection of cardiovascular and cerebrovascular, anti-inflammation, antioxidant, and more. This review illustrates ISO's antitumor and other pharmacological potentials, providing a theoretical basis for further research and new drug development of ISO.

15.
Med Image Anal ; 95: 103173, 2024 Apr 09.
Article En | MEDLINE | ID: mdl-38657424

Quantitative susceptibility mapping (QSM) is an MRI-based technique that estimates the underlying tissue magnetic susceptibility based on phase signal. Deep learning (DL)-based methods have shown promise in handling the challenging ill-posed inverse problem for QSM reconstruction. However, they require extensive paired training data that are typically unavailable and suffer from generalization problems. Recent model-incorporated DL approaches also overlook the non-local effect of the tissue phase in applying the source-to-field forward model due to patch-based training constraint, resulting in a discrepancy between the prediction and measurement and subsequently suboptimal QSM reconstruction. This study proposes an unsupervised and subject-specific DL method for QSM reconstruction based on implicit neural representation (INR), referred to as INR-QSM. INR has emerged as a powerful framework for learning a high-quality continuous representation of the signal (image) by exploiting its internal information without training labels. In INR-QSM, the desired susceptibility map is represented as a continuous function of the spatial coordinates, parameterized by a fully-connected neural network. The weights are learned by minimizing a loss function that includes a data fidelity term incorporated by the physical model and regularization terms. Additionally, a novel phase compensation strategy is proposed for the first time to account for the non-local effect of tissue phase in data consistency calculation to make the physical model more accurate. Our experiments show that INR-QSM outperforms traditional established QSM reconstruction methods and the compared unsupervised DL method both qualitatively and quantitatively, and is competitive against supervised DL methods under data perturbations.

17.
World J Diabetes ; 15(4): 645-653, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38680689

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have large fluctuations in blood glucose (BG), abnormal metabolic function and low immunity to varying degrees, which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy. Controlling hyperglycemia may have important therapeutic implications for cancer patients. AIM: To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma (LC). METHODS: The clinical data of 60 T2DM + LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed. All patients underwent chemotherapy and were grouped as a control group (CG; normal BG fluctuation with a mean fluctuation < 3.9 mmol/L) and an observation group (OG; high BG fluctuation with a mean fluctuation ≥ 3.9 mmol/L) based on their BG fluctuations, with 30 cases each. BG-related indices, tumor markers, serum inflammatory cytokines and adverse reactions were comparatively analyzed. Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers. RESULTS: The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG, together with markedly higher mean amplitude of glycemic excursions (MAGE), mean of daily differences, largest amplitude of glycemic excursions and standard deviation of blood glucose (P < 0.05). In addition, the OG exhibited evidently higher levels of carbohydrate antigen 19-9, carbohydrate antigen 125, carcinoembryonic antigen, neuron-specific enolase, cytokeratin 19, tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein than the CG (P < 0.05). Pearson analysis revealed a positive association of MAGE with serum tumor markers. The incidence of adverse reactions was significantly higher in the OG than in the CG (P < 0.05). CONCLUSION: The greater the BG fluctuation in LC patients after chemotherapy, the more unfavorable the therapeutic effect of chemotherapy; the higher the level of tumor markers and inflammatory cytokines, the more adverse reactions the patient experiences.

18.
Front Biosci (Landmark Ed) ; 29(4): 156, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38682211

BACKGROUND: Environmental conditions, such as photoperiod, affect the developmental response of plants; thus, plants have evolved molecular mechanisms to adapt to changes in photoperiod. In Bougainvillea spp., the mechanism of flower formation underlying flowering control techniques remains poorly understood, and the physiological changes that occur during flower bud formation and the expression of related genes are not yet fully understood. METHODS: In this study, we induced flowering of potted Bougainvillea glabra 'Sao Paulo' plants under light-control treatments and analyzed their effects on flowering time, number of flower buds, flowering quality, as well as quality of flower formation, which was analyzed using transcriptome sequencing. RESULTS: Light-control treatment effectively induced the rapid formation of flower buds and early flowering in B. glabra 'Sao Paulo', with the time of flower bud formation being 119 days earlier and the flowering period extended six days longer than those of the control plants. The light-control treatment caused the bracts to become smaller and lighter in color, while the number of flowers increased, and the neatness of flowering improved. Transcriptome sequencing of the apical buds identified 1235 differentially expressed genes (DEGs) related to the pathways of environmental adaptation, biosynthesis of other secondary metabolites, glycan biosynthesis and metabolism, and energy metabolism. DEGs related to gibberellin metabolism were analyzed, wherein five DEGs were identified between the control and treatment groups. Transcriptomic analysis revealed that the gibberellin regulatory pathway is linked to flowering. Specifically, GA and GID1 levels increased during this process, enhancing DELLA protein degradation. However, decreasing this protein's binding to CO did not halt FT upregulation, thereby advancing the flowering of B. glabra 'Sao Paulo'. CONCLUSIONS: The findings of our study have implications for future research on photoperiod and its role in controlling flowering timing of Bougainvillea spp.


Flowers , Gene Expression Regulation, Plant , Photoperiod , Flowers/genetics , Flowers/growth & development , Flowers/metabolism , Nyctaginaceae/genetics , Nyctaginaceae/growth & development , Nyctaginaceae/metabolism , Transcriptome , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Profiling
19.
PLoS One ; 19(4): e0300535, 2024.
Article En | MEDLINE | ID: mdl-38683846

Recent studies suggest a shared genetic architecture between muscle and bone, yet the underlying molecular mechanisms remain elusive. This study aims to identify the functionally annotated genes with shared genetic architecture between muscle and bone using the most up-to-date genome-wide association study (GWAS) summary statistics from bone mineral density (BMD) and fracture-related genetic variants. We employed an advanced statistical functional mapping method to investigate shared genetic architecture between muscle and bone, focusing on genes highly expressed in muscle tissue. Our analysis identified three genes, EPDR1, PKDCC, and SPTBN1, which are highly expressed in muscle tissue and previously unlinked to bone metabolism. About 90% and 85% of filtered Single-Nucleotide Polymorphisms were in the intronic and intergenic regions for the threshold at P≤5×10-8 and P≤5×10-100, respectively. EPDR1 was highly expressed in multiple tissues, including muscles, adrenal glands, blood vessels, and the thyroid. SPTBN1 was highly expressed in all 30 tissue types except blood, while PKDCC was highly expressed in all 30 tissue types except the brain, pancreas, and skin. Our study provides a framework for using GWAS findings to highlight functional evidence of crosstalk between multiple tissues based on shared genetic architecture between muscle and bone. Further research should focus on functional validation, multi-omics data integration, gene-environment interactions, and clinical relevance in musculoskeletal disorders.


Bone Density , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Spectrin , Humans , Bone and Bones/metabolism , Bone Density/genetics , Spectrin/genetics , Spectrin/metabolism
20.
Medicine (Baltimore) ; 103(12): e37117, 2024 Mar 22.
Article En | MEDLINE | ID: mdl-38518022

Helicobacter pylori (H pylori) infection was common worldwide and previous researches on the correlation between H pylori infection and metabolic abnormality provided inconsistent conclusions. We assessed acute H pylori infection prevalence and the relationship with metabolic abnormality in general Chinese population. Participants attending for the physical examination underwent a carbon-13 urea breath test. For individual, the following data were collected: age, gender, body mass index (BMI), systolic blood pressure, diastolic blood pressure, total protein, albumin, globulin (GLB), total bilirubin, direct bilirubin (DBIL), indirect bilirubin, alanine transaminase, glutamyl transpeptidase, alkaline phosphatase, cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, urea nitrogen, creatinine, uric acid, fasting plasma glucose (FPG), and homocysteine. A total of 29,154 participants were enrolled. The prevalence of acute H pylori infection was 29.79% (8684/29,154). Spearson correlation analysis showed that gender, BMI, ALB, GLB, total bilirubin, DBIL, indirect bilirubin, and FPG were closely related to H pylori infection. Multinomial logistic regressions analysis with stepwise subset selection further identified gender, BMI, ALB, GLB, DBIL, and FPG as independent risk factors for acute H pylori infection. Our results indicated that acute H pylori infection might has a significant impact on metabolic abnormalities, which should be further confirmed.


Helicobacter Infections , Helicobacter pylori , Humans , Retrospective Studies , Helicobacter Infections/complications , Prevalence , Risk Factors , Cholesterol, HDL , Urea , Bilirubin , China/epidemiology
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