APOA2: New Target for Molecular Hydrogen Therapy in Sepsis-Related Lung Injury Based on Proteomic and Genomic Analysis.

Target biomarkers for H2 at both the protein and genome levels are still unclear. In this study, quantitative proteomics acquired from a mouse model were first analyzed. At the same time, functional pathway analysis helped identify functional pathways at the protein level. Then, bioinformatics on mRNA sequencing data were conducted between sepsis and normal mouse models. Differential expressional genes with the closest relationship to disease status and development were identified through module correlation analysis. Then, common biomarkers in proteomics and transcriptomics were extracted as target biomarkers. Through analyzing expression quantitative trait locus (eQTL) and genome-wide association studies (GWAS), colocalization analysis on Apoa2 and sepsis phenotype was conducted by summary-data-based Mendelian randomization (SMR). Then, two-sample and drug-target, syndrome Mendelian randomization (MR) analyses were all conducted using the Twosample R package. For protein level, protein quantitative trait loci (pQTLs) of the target biomarker were also included in MR. Animal experiments helped validate these results. As a result, Apoa2 protein or mRNA was identified as a target biomarker for H2 with a protective, causal relationship with sepsis. HDL and type 2 diabetes were proven to possess causal relationships with sepsis. The agitation and inhibition of Apoa2 were indicated to influence sepsis and related syndromes. In conclusion, we first proposed Apoa2 as a target for H2 treatment.

[Heart sound classification based on improved mel frequency cepstrum coefficient and integrated decision network method].

Heart sound analysis is significant for early diagnosis of congenital heart disease. A novel method of heart sound classification was proposed in this paper, in which the traditional mel frequency cepstral coefficient (MFCC) method was improved by using the Fisher discriminant half raised-sine function (F-HRSF) and an integrated decision network was used as classifier. It does not rely on segmentation of the cardiac cycle. Firstly, the heart sound signals were framed and windowed. Then, the features of heart sounds were extracted by using improved MFCC, in which the F-HRSF was used to weight sub-band components of MFCC according to the Fisher discriminant ratio of each sub-band component and the raised half sine function. Three classification networks, convolutional neural network (CNN), long and short-term memory network (LSTM), and gated recurrent unit (GRU) were combined as integrated decision network. Finally, the two-category classification results were obtained through the majority voting algorithm. An accuracy of 92.15%, sensitivity of 91.43%, specificity of 92.83%, corrected accuracy of 92.01%, and F score of 92.13% were achieved using the novel signal processing techniques. It shows that the algorithm has great potential in early diagnosis of congenital heart disease.

Alterations of brain metrics in fetuses of women with polycystic ovary syndrome : a retrospective study based on fetal magnetic resonance imaging.

BACKGROUND: Maternal polycystic ovary syndrome (PCOS) has potential detrimental effects on the neurodevelopment of offspring. This study aimed to evaluate the brain metrics in fetuses of women with PCOS based on fetal magnetic resonance imaging (MRI). METHODS: This retrospective study included 60 pregnant women with PCOS (PCOS group) and 120 pregnant non-PCOS women (control group). Fetal MRI was performed followed an ultrasound and for numerous clinical indications including known or suspected fetal pathology, history of fetal abnormality in previous pregnancy or in a family member. Fetal brain biometry and apparent diffusion coefficient (ADC) value were analysed. RESULTS: After adjusting for potential confounders, fetuses in the PCOS group showed the following characteristics compared to fetuses in the control group: (1) smaller cerebral fronto-occipital diameter (FOD), vermian height (VH) and anteroposterior diameter of the pons (APDP) (evident before 32 weeks; P = 0.042, P = 0.002 and P = 0.016, respectively); (2) larger left and right biparietal index (evident before 32 weeks; P = 0.048 and P = 0.025, respectively); (3) smaller left lateral ventricle (LV) (evident after 32 weeks; P = 0.005); (4) larger anteroposterior diameter of the vermis (APDV) and hippocampal infolding angle (HIA) (evident after 32 weeks; P = 0.003 and P < 0.001, respectively); (5) higher ADC value in frontal white matter (FWM) and in basal ganglia (BG) (evident before and after 32 weeks; all P < 0.05). CONCLUSIONS: There exist a different pattern of brain metrics in PCOS offspring in utero.

Normobaric hyperoxia plays a protective role against renal ischemia-reperfusion injury by activating the Nrf2/HO-1 signaling pathway.

Following renal ischemia-reperfusion injury (RIRI), because of the decrease in oxygen supply to the kidney, a large amount of oxygen-free radicals is generated, and in severe cases, tissue cells will undergo apoptosis or even die. Normobaric hyperoxia (NBHO) is a very common clinical adjuvant treatment. It restores the oxygen supply after renal ischemia and combats oxidative stress in tissues, thus playing a protective role. In this study, our aim is to elucidate the protective mechanism of NBHO inhalation in a rat RIRI model. We performed a surgical excision of the left kidney of the rat and established a right kidney solitary kidney model. Later, the right renal pedicle of the rat was clamped using a non-invasive vascular clamp for 45 min. After the vascular clamp was released and reperfused for 24 h, the rat was placed in a closed oxygen chamber. It was subjected to inhalation of high-concentration oxygen (50%-55%), 2 h daily, for 7 days.RIRI induces postoperative weight loss, impaired renal function, increased oxygen free radicals, reduced antioxidant substances, increased histopathological damage, and increased levels of apoptosis. These effects were significantly improved after treatment with NBHO. At the same time, NBHO significantly increased the expression levels of Nrf2 and HO-1 in the tissues after RIRI. To verify whether HO-1 induced by Nrf2 is involved in the resistance to oxidative stress, after the rat RIRI and before inhaling NBHO, we intraperitoneally injected HO-1 specific inhibitor zinc protoporphyrin (ZnPP) (45 µmol/Kg). However, we found that ZnPP reversed the protective effect of NBHO on RIRI in rats. Combining all the results, we have demonstrated the protective effect of NBHO on RIRI, which can be at least partially attributed to the activation of the Nrf2/HO-1 antioxidative stress pathway.

Outcomes of Treatment for Elderly Patients With Trigeminal Neuralgia: Percutaneous Balloon Compression Versus Microvascular Decompression.

OBJECTIVE: The study aimed to evaluate the surgical outcomes of percutaneous balloon compression (PBC) and microvascular decompression (MVD) in the treatment of elderly patients with trigeminal neuralgia (TN). METHODS: A total of 30 patients who underwent PBC surgery (PBC group) and 30 patients who received MVD surgery (MVD group) were included. The treatment efficacy, Barrow Neurological Institute (BNI) pain intensity score, inflammatory response, the rates of complication and recurrence were analyzed respectively. RESULTS: The total efficacy was 93.33% in the PBC group and 90.00% in the MVD group (P > 0.05), respectively. The pain relief rate was 90.00% and 86.67% after PBC and MVD surgery, respectively (P > 0.05). The levels of IL-1ß, TNF-α, and IL-6 were significantly decreased at post-operative 3 days and 5 days compared with pre-operation in the 2 groups (P < 0.05). The post-operative complication rates regarding masticatory muscle weakness and facial numbness in the PBC group were higher than MVD group (P < 0.05). Nevertheless, the incidences of herpes simplex and keratohelcosis were similar between the 2 groups (P > 0.05). The recurrence rates were also similar between the 3 groups (P > 0.05). CONCLUSION: Percutaneous balloon compression and MVD are effective in the treatment for elderly TN, which can effectively improve the post-operative cure rate of pain prognosis and reduce the inflammatory response. However, PBC is a minimally invasive, safe and effective method for patients in poor general condition and refused treatment with craniotomy.

The efficacy and safety of retroperitoneoscopic renal pedicle ligation of lymphatic disconnection versus open surgery in the treatment of chyluria: A systematic review and meta-analysis
.

OBJECTIVE: The current meta-analysis was performed to evaluate the safety and efficacy of retroperitoneoscopic renal pedicle ligation of lymphatic disconnection (RRPLD) compared with open surgery (OS) in the treatment of chyluria. MATERIALS AND METHODS: Relevant studies were retrieved from MEDLINE, EMBASE, -SCOPUS, the Cochrane library and two Chinese literature database resources (Wanfang and CNKI) in March 2016. All eligible studies comparing RRPLD with OS for chyluria were included in this study. The main outcome including operative time, blood loss, postoperative (PO) intestinal recovery time, PO drainage duration, PO hospital stay, PO time of returning to work, PO bed time, and complications as well as rate of recurrence for RRPLD and OS were pooled using the Revman software. RESULTS: Twelve studies with a total of 620 patients were included in this meta-analysis. Of these patients, 365 and 255 had undergone renal pedicle lymphatic ligation via RRPLD and OS, respectively. There were significant reductions in operative time, PO intestinal recovery time, PO drainage duration, PO hospital stay, PO time of returning to work, and possible reductions in intraoperative blood loss intraoperative and PO complications for RRPLD compared to OS. However, other outcome variables, such as PO time in bed and PO recurrence, were not found to be statistically significant for either group. CONCLUSION: Compared with OS, RRPLD has several advantages such as shorter operative time, less intraoperative blood loss, and lower incidence of complications. Thus, it may be an efficacious and safe therapeutic modality for chyluria.

Annexin A10 contributes to chronic constrictive injury-induced pain through activating ERK1/2 signalling in rats.

PURPOSE: The current study aims at investigating the downstream targets of spinal Annexin A10 in modulating neuropathic pain. MATERIALS AND METHODS: Paw withdrawal latency and paw withdrawal threshold were measured to evaluate the pain-associated behaviour in rats. The expression of spinal Annexin A10, phosphorylated-extracellular regulated kinase 1/2 and extracellular regulated kinase were detected by western blotting. The level of tumour necrosis factor-α and interleukine-1ß was tested by enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Chronic constrictive injury caused pain hypersensitivity in rats, along with increased expression of spinal Annexin A10, phosphorylated-extracellular regulated kinase 1/2, tumour necrosis factor-α and interleukine-1ß in rats. Knockdown of spinal Annexin A10 suppressed the chronic constrictive injury-induced hyperalgesia, and inhibited the chronic constrictive injury-induced increased expression of phosphorylated-extracellular regulated kinase 1/2, tumour necrosis factor-α and interleukine-1ß in the spinal cord. Inhibition of spinal extracellular regulated kinase activation decreased the release of tumour necrosis factor-α and interleukine-1ß, but did not change the increased expression of Annexin A10 caused by chronic constrictive injury. CONCLUSIONS: Annexin A10 contributed to the development of neuropathic pain by activating spinal extracellular regulated kinase signalling and the subsequent release of tumour necrosis factor-α and interleukine-1ß in the spinal cord.

Phase-Transition Induced Conversion into a Photothermal Material: Quasi-Metallic WO2.9 Nanorods for Solar Water Evaporation and Anticancer Photothermal Therapy.

Phase transition from WO3 to sub-stoichiometric WO2.9 by a facile method has varied the typical semiconductor to be quasi-metallic with a narrowed band gap and a shifted Femi energy to the conduction band, while maintaining a high crystallinity. The resultant WO2.9 nanorods possess a high total absorption capacity (ca. 90.6 %) over the whole solar spectrum as well as significant photothermal conversion capability, affording a conversion efficiency as high as around 86.9 % and a water evaporation efficiency of about 81 % upon solar light irradiation. Meanwhile, the promising potential of the nanorods for anticancer photothermal therapy have been also demonstrated, with a high photothermal conversion efficiency (ca. 44.9 %) upon single wavelength near-infrared irradiation and a high tumor inhibition rate (ca. 98.5 %). This study may have opened up a feasible route to produce high-performance photothermal materials from well-developed oxides.

Effect of alpha1-blockers on stentless ureteroscopic lithotripsy.

OBJECTIVE: To evaluate the clinical efficiency of alpha1-adrenergic antagonists on stentless ureteroscopic lithotripsy treating uncomplicated lower ureteral stones. MATERIALS AND METHODS: From January 2007 to January 2013, 84 patients who have uncomplicated lower ureteral stones treated by ureteroscopic intracorporeal lithotripsy with the holmium laser were analyzed. The patients were divided into two groups, group A (44 patients received indwelled double-J stents) and group B (40 patients were treated by alpha1-adrenergic antagonists without stents). All cases of group B were treated with alpha1 blocker for 1 week. RESULTS: The mean operative time of group A was significantly longer than group B. The incidences of hematuria, flank/abdominal pain, frequency/urgency after surgery were statistically different between both groups. The stone-free rate of each group was 100%. CONCLUSIONS: The effect of alpha1-adrenergic antagonists is more significant than indwelling stent after ureteroscopic lithotripsy in treating uncomplicated lower ureteral stones.

Pten Inhibitor-bpV Ameliorates Early Postnatal Propofol Exposure-Induced Memory Deficit and Impairment of Hippocampal LTP.

Early postnatal propofol administration has potential detrimental effects on hippocampal synaptic development and memory. Therapeutic method is still lack due to unknown mechanisms. In this study, a 7-day propofol protocol was applied to model anesthesia in neonatal mice. Phosphatase and tensin homolog deleted on chromosome ten (Pten) inhibitor bisperoxovanadium (bpV) was pre-applied before propofol to study its potential protection. After propofol application, Pten level increased while phospho-AKT (p-AKT) (Ser473) decreased in dorsal hippocampus. Interestingly, i.p. injection of Pten inhibitor reversed the decrease of p-AKT. Two months after administration, basal synaptic transmission, hippocampal long-term potentiation (LTP) and long-term memory were reduced in propofol-administrated mice. By contrast, i.p. injection of Pten inhibitor at a dose of 0.2 mg/kg/day before propofol reversed the detrimental effects due to propofol application. Consistently, bpV injection also reversed propofol application-induced decrease of synaptic plasticity-related proteins, including p-CamKIIα, p-PKA and postsynaptic density protein 95. Taken together, our results demonstrate that bpV injection could reverse early propofol exposure-induced decrease of memory and hippocampal LTP. bpV might be a potential therapeutic for memory impairment after early propofol postnatal application.

A prospective comparative study of haemodynamic, electrolyte, and metabolic changes during percutaneous nephrolithotomy and minimally invasive percutaneous nephrolithotomy.

OBJECTIVES: To report the haemodynamic, electrolyte, and metabolic changes of a prospective clinical trial comparing minimally invasive percutaneous nephrolithotomy (MPCNL) with percutaneous nephrolithotomy (PCNL) for renal stones. METHODS: In all, 71 patients who had undergone MPCNL (37) or PCNL (34) were prospectively assessed. Heart rate and arterial blood pressure were monitored, and samples for electrolyte estimation and arterial blood gas analysis were drawn at the start, 30th, 60th, 90th, and 120th min of irrigation and 24 h later after both procedures. RESULTS: In the PCNL group, no significant changes occurred in heart rate, arterial blood pressure, electrolytes, and pH. In the MPCNL group, heart rate, arterial blood pressure, and serum sodium levels kept stably during and after irrigation; the decrease in potassium levels was found from the 30th to 120th min of irrigation and did not recovery until 24 h later after operation (P < 0.05), but the potassium levels was normal during the entire observation period; the increase in Cl(-) levels was noted at the 120th min of irrigation (P < 0.05); there was a decreasing trend of pH from the start to the 120th min of irrigation (P < 0.05) and 24 h later after operation this trend attenuated (P < 0.05); the changes in base excess levels were in accordance with those in pH levels. CONCLUSIONS: Although haemodynamic and electrolyte changes remains stable, a trend towards metabolic acidosis is obvious as the irrigation time goes by during MPCNL compared with PCNL. Therefore, arterial blood gases should be monitored during and after MPCNL in patients with prolonged irrigation time.

Long-term relapse-free survival enabled by integrating targeted antibacteria in antitumor treatment.

The role of tumor-resident intracellular microbiota (TRIM) in carcinogenesis has sparked enormous interest. Nevertheless, the impact of TRIM-targeted antibacteria on tumor inhibition and immune regulation in the tumor microenvironment (TME) remains unexplored. Herein, we report long-term relapse-free survival by coordinating antibacteria with antitumor treatment, addressing the aggravated immunosuppression and tumor overgrowth induced by TRIM using breast and prostate cancer models. Combining Ag+ release with a Fenton-like reaction and photothermal conversion, simultaneous bacteria killing and multimodal antitumor therapy are enabled by a single agent. Free of immune-stimulating drugs, the agent restores antitumor immune surveillance and activates immunological responses. Secondary inoculation and distal tumor analysis confirm lasting immunological memory and systemic immune responses. A relapse-free survival of >700 days is achieved. This work unravels the crucial role of TRIM-targeted antibacteria in tumor inhibition and unlocks an unconventional route for immune regulation in TME and a complete cure for cancer.

GSTT1 null genotype is associated with an increased risk of prostate cancer in caucasians: a meta-analysis.

BACKGROUND: Many studies have investigated the association between glutathione S-transferase T1 (GSTT1) null genotype and the risk of prostate cancer (PCa), but the impact of GSTT1 null genotype on PCa risk in Caucasians is still unclear owing to the inconsistency of such studies. The present study aimed to quantify the strength of association between GSTT1 null genotype and the risk of PCa in Caucasians. METHODS: We searched the PubMed, Embase and Web of Science databases for studies assessing the association between GSTT1 null genotype and the risk of PCa in Caucasians. We estimated the summary odds ratio (OR) with the corresponding 95% confidence interval (95% CI) to assess the association. RESULTS: 16 case-control studies with 11,648 subjects were included in this meta-analysis. Meta-analysis of a total of 16 studies showed GSTT1 null genotype was significantly associated with an increased risk of PCa in Caucasians (random-effects OR 1.30, 95% CI 1.10-1.53, p = 0.002). After adjustment for heterogeneity, GSTT1 null genotype was still associated with an increased risk of PCa in Caucasians (fixed-effects OR 1.33, 95% CI 1.17-1.52, p < 0.001). The cumulative meta-analyses of all 16 studies showed a trend of more obvious association as information accumulated by year. CONCLUSIONS: Meta-analysis of available data suggests the GSTT1 null genotype is significantly associated with an increased risk of PCa in Caucasians.

Unusual DNA structures formed on bare highly oriented pyrolytic graphite surfaces studied by atomic force microscopy.

It is important to know the detailed DNA structure on carbonaceous surfaces for further application of DNA-functionalized carbonaceous materials in diverse research areas. In this study, the topographic and structural characteristics of the separated single DNA molecules and their assembly on highly oriented pyrolytic graphite (HOPG) surfaces have been investigated by atomic force microscopy (AFM). AFM results indicate that both circular and linear DNA molecules tend to form hexagonal patterns along with some unusual structures that include node, protrusion, cruciform, parallel single-stranded DNA (ssDNA), and compact zigzag. Furthermore, parallel ssDNA patterns and their crossed structures have been obtained under high-temperature conditions. Our AFM results reveal that a bare HOPG surface can induce DNA molecules to form various unusual structures. This finding is helpful for understanding the adsorption behavior of DNA on other carbonaceous surfaces such as carbon nanotubes and graphene. In addition, the hexagonal DNA patterns in this study are similar to those formed on the alkylamine-modified HOPG surface, which implies that a bare HOPG, without any chemical modification, has a strong ability to align biomolecules. This study could expand our knowledge of the diversities of DNA structures and the aligning ability of carbonaceous surfaces.

Assistive diagnostic technology for congenital heart disease based on fusion features and deep learning.

Introduction: Congenital heart disease (CHD) is a cardiovascular disorder caused by structural defects in the heart. Early screening holds significant importance for the effective treatment of this condition. Heart sound analysis is commonly employed to assist in the diagnosis of CHD. However, there is currently a lack of an efficient automated model for heart sound classification, which could potentially replace the manual process of auscultation. Methods: This study introduces an innovative and efficient screening and classification model, combining a locally concatenated fusion approach with a convolutional neural network based on coordinate attention (LCACNN). In this model, Mel-frequency spectral coefficients (MFSC) and envelope features are locally fused and employed as input to the LCACNN network. This model automatically analyzes feature map energy information, eliminating the need for denoising processes. Discussion: The proposed classification model in this study demonstrates a robust capability for identifying congenital heart disease, potentially substituting manual auscultation to facilitate the detection of patients in remote areas. Results: This study introduces an innovative and efficient screening and classification model, combining a locally concatenated fusion approach with a convolutional neural network based on coordinate attention (LCACNN). In this model, Mel-frequency spectral coefficients (MFSC) and envelope features are locally fused and employed as input to the LCACNN network. This model automatically analyzes feature map energy information, eliminating the need for denoising processes. To assess the performance of the classification model, comparative ablation experiments were conducted, achieving classification accuracies of 91.78% and 94.79% on the PhysioNet and HS databases, respectively. These results significantly outperformed alternative classification models.

Advances in the relationship between ferroptosis and epithelial-mesenchymal transition in cancer.

Epithelial-mesenchymal transition (EMT) is a cellular reprogramming process that converts epithelial cells into mesenchymal-like cells with migratory and invasive capabilities. The initiation and regulation of EMT is closely linked to a range of transcription factors, cell adhesion molecules and signaling pathways, which play a key role in cancer metastasis and drug resistance. The regulation of ferroptosis is intricately linked to various cell death pathways, intracellular iron homeostasis, and the protein network governing iron supply and storage. The ability of ferroptosis to disrupt cancer cells and overcome drug resistance lies in its control of intracellular iron ion levels. EMT process can promote the accumulation of iron ions, providing conditions for ferroptosis. Conversely, ferroptosis may impact the regulatory network of EMT by modulating transcription factors, signaling pathways, and cell adhesion molecules. Thus, ferroptosis related genes and signaling pathways and oxidative homeostasis play important roles in the regulation of EMT. In this paper, we review the role of ferroptosis related genes and their signaling pathways in regulating cancer EMT to better understand the crosstalk mechanism between ferroptosis and EMT, aiming to provide better therapeutic strategies for eradicating cancer cells and overcoming drug resistance.

Preoperative prediction of sonic hedgehog and group 4 molecular subtypes of pediatric medulloblastoma based on radiomics of multiparametric MRI combined with clinical parameters.

Purpose: To construct a machine learning model based on radiomics of multiparametric magnetic resonance imaging (MRI) combined with clinical parameters for predicting Sonic Hedgehog (SHH) and Group 4 (G4) molecular subtypes of pediatric medulloblastoma (MB). Methods: The preoperative MRI images and clinical data of 95 patients with MB were retrospectively analyzed, including 47 cases of SHH subtype and 48 cases of G4 subtype. Radiomic features were extracted from T1-weighted imaging (T1), contrast-enhanced T1 weighted imaging (T1c), T2-weighted imaging (T2), T2 fluid-attenuated inversion recovery imaging (T2FLAIR), and apparent diffusion coefficient (ADC) maps, using variance thresholding, SelectKBest, and Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithms. The optimal features were filtered using LASSO regression, and a logistic regression (LR) algorithm was used to build a machine learning model. The receiver operator characteristic (ROC) curve was plotted to evaluate the prediction accuracy, and verified by its calibration, decision and nomogram. The Delong test was used to compare the differences between different models. Results: A total of 17 optimal features, with non-redundancy and high correlation, were selected from 7,045 radiomics features, and used to build an LR model. The model showed a classification accuracy with an under the curve (AUC) of 0.960 (95% CI: 0.871-1.000) in the training cohort and 0.751 (95% CI: 0.587-0.915) in the testing cohort, respectively. The location of the tumor, pathological type, and hydrocephalus status of the two subtypes of patients differed significantly (p < 0.05). When combining radiomics features and clinical parameters to construct the combined prediction model, the AUC improved to 0.965 (95% CI: 0.898-1.000) in the training cohort and 0.849 (95% CI: 0.695-1.000) in the testing cohort, respectively. There was a significant difference in the prediction accuracy, as measured by AUC, between the testing cohorts of the two prediction models, which was confirmed by Delong's test (p = 0.0144). Decision curves and nomogram further validate that the combined model can achieve net benefits in clinical work. Conclusion: The combined prediction model, constructed based on radiomics of multiparametric MRI and clinical parameters can potentially provide a non-invasive clinical approach to predict SHH and G4 molecular subtypes of MB preoperatively.

Analysis of Zinc and Stromal Immunity in Disuse Osteoporosis: Mendelian Randomization and Transcriptomic Analysis.

OBJECTIVE: Disuse osteoporosis is known to be primarily caused by a lack of exercise. However, the causal relationships between zinc and immunity and disuse osteoporosis remain unknown. This study investigated these relationships and their potential mechanisms. METHODS: This study was an integrative study combining genome-wide association studies and transcriptomics. Two-sample Mendelian randomization analysis (MR) was used to analyze the causal relationships between exposures (zinc, immunity, physical activity) and the outcome (osteoporosis) with the aid of single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Four models, MR-Egger, inverse variance weighted, weighted median and MR-Pleiotrophy RESidual Sum and Outlier (MRPRESSO), were used to calculate odds ratio values. Sensitivity and heterogeneity analyses were also performed using MRPRESSO and MR-Egger methods. The mRNA transcriptomic analysis was subsequently conducted. Zinc metabolism scores were acquired through single-sample Gene Set Enrichment Analysis algorithms. Stromal scores were obtained using the R Package "estimate" algorithms. Important Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathways were also derived through gene set variation analysis. Cytoscape software helped construct the transcription factor (TF)-mRNA-microRNA (miRNA) network. Virtual screening and molecular docking were performed. Polymerase chain reaction validation was also carried out in vivo. RESULTS: Causal relationships were demonstrated between zinc and exercise (95% confidence interval [CI] = 1.30-2.95, p = 0.001), exercise and immunity (95% CI = 0.36-0.80, p = 0.002), exercise and osteoporosis (95% CI = 0.97-0.99, p = 0.0007), and immunity disorder and osteoporosis (95% CI = 1.30-2.03, p = 0.00002). One hundred and seventy-nine mRNAs in important modules were screened. Combining the differential expressional genes (DEGs) and the Boruta selection, six DEGs were screened (AHNAK, CSF2, ADAMTS12, SRA1, RUNX2, and SLC39A14). TF HOXC10 and miRNA hsa-miR-204 were predicted. Then, the TF-mRNA-miRNA network was successfully constructed. RUNX2 and SLC39A14 were identified as hub mRNAs in the TF-mRNA-miRNA network. Eventually, the novel small drug C6O4NH5 was designed according to the pharmacophore structure of SLC39A14. The docking energy for the novel drug was -5.83 kcal/mol. SLC39A14 and RUNX2 were downregulated (of statistical significance p-value < 0.05) in our animal experiment. CONCLUSION: This study revealed that zinc had a protective causal relationship with disuse osteoporosis by promoting exercise and immunity. SLC39A14 and RUNX2 mRNA participated in this zinc-related mechanism.

The value of cardiac magnetic resonance imaging in endocardial fibroelastosis.

Introduction: Endocardial fibroelastosis (EFE), an uncommon congenital heart disorder often occurring in infants, has a poor prognosis. It is of great significance to perform early diagnosis and accurately analyze cardiac function to enable further clinical treatment and prognosis decisions. This study aimed to explore the findings of cardiac magnetic resonance (CMR) in patients with EFE, including morphological changes and cardiac function analyses. Additionally, we compared the difference in the evaluation of the cardiac function between CMR and echocardiography (Echo). Methods: Eleven patients with EFE (nine females and two males, aged between 0.3 and 1.9 years), treated in our hospital, were analyzed retrospectively. Left ventricular posterior wall thickness (LVPW), anterior wall thickness (LVAW), fractional shortening (FS), ejection fraction (EF), end-systolic diameter (ESD), end-diastolic diameter (EDD), end-systolic volume (ESV), and end-diastolic volume (EDV) were assessed using both Echo and CMR. The Original Ross classification and the New York Heart Association functional classification were used to grade the patients' cardiac function. The correlations between clinical cardiac function classification and MRI- and Echo-derived imaging data were determined. Results: All patients showed a thickened endocardium and left ventricle globular dilatation on CMR. We observed significant systolic dysfunction and whole or segmental abnormal ventricular movement. Compared with those measured by Echo, the EF, FS, and EDV values were significantly lower when measured using CMR. Compared with Echo measurements, the ESV, ESD, LVAW, and LVPW values were significantly higher when measured using CMR. CMR-measured EF and FS correlated better with the clinical cardiac functional score than those derived from Echo (EF, r = 0.646 > 0.224; FS, r = 0.627 > 0.245, respectively). Conclusion: In patients with EFE, the characteristic morphological changes of the heart could be displayed accurately using CMR. The parameters measured by CMR were more accurate than those of Echo and correlated well with clinical cardiac function scores, mainly because it does not make invalid geometrical assumptions.