Investigation of Altered Spontaneous Brain Activity Patterns in Herpes Zoster Keratitis Using the Percent Amplitude of Fluctuation Method: A Resting-State Functional Magnetic Resonance Imaging Study.

Purpose: The purpose of this study was to use the percent amplitude of fluctuation (PerAF) to study the changes in brain activity and nerve function of herpes zoster keratitis (HZK) patients. Methods: We recruited 20 HZK patients and 20 healthy controls (HCs). Each of these groups included ten males and ten females and were matched in weight and age. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). The percent amplitude of fluctuation (PerAF) method was used for analysis and detected differences between the two groups in the neurological function of brain areas. We also applied the receiver operating characteristic (ROC) curve to analyze the two groups and did a correlation analysis between the PerAF value, anxiety and depression score, and visual acuity. Results: The PerAF signal at the right putamen and right precentral gyrus was significantly higher in patients than in HCs. However, the PerAF value of the left inferior temporal was lower in patients than in HCs. In addition, the HZK patients' anxiety and depression score (HADS) and visual acuity (V.A.) Log MAR negatively correlated with the PerAF value at the left inferior temporal gyrus. Conclusion: HZK patients had some changes in brain regions, and the changes were also related to their mood and visual acuity. These findings might contribute to other studies on the potential pathological mechanism, disease development, prognosis, and brain function in HZK patients.

A Chinese scoring system for predicting successful retrograde collateral traverse in patients with chronic total coronary occlusion.

BACKGROUND: Retrograde approach technique has been challenging in percutaneous coronary interventional treatment of chronic total occlusion (CTO) coronary disease. The present study endeavors to determine a novel Chinese scoring system for predicting successful collateral channels traverse via retrograde approach. METHODS: The demographic characteristics and angiographic characteristics of 309 CTO patient were analyzed by univariable and multivariable analysis for selecting potential predictors. And the nomogram was used to establish the scoring system. Then it was evaluated by the internal and external validation. RESULTS: The predictors of Age, Connections between collateral channels and recipient vessels, and Channel Tortuosity (ACT) were identified with univariable and multivariable analysis and employed to the ACT score system. With acceptable calibrations, the area under curve of the scoring system and the external validation were 0.826 and 0.816 respectively. Based on score, the predictors were divided into three risk categories and it showed a consistent prediction power in the validation cohort. CONCLUSIONS: The novel Chinese ACT score is a reliable tool for predicting successful retrograde collateral traverse.

Allergic bronchopulmonary aspergillosis with marked peripheral blood eosinophilia and pulmonary eosinophilia: A case report.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an immune-related pulmonary disease caused by sensitization of airway by Aspergillus fumigatus. The disease manifests as bronchial asthma and recurring pulmonary shadows, which may be associated with bronchiectasis. The diagnosis of ABPA mainly depends on serological, immunological, and imaging findings. Pathological examination is not necessary but may be required in atypical cases to exclude pulmonary tuberculosis, tumor, and other diseases through lung biopsy. CASE SUMMARY: An 18-year-old man presented with recurrent wheezing, cough, and peripheral blood eosinophilia. Chest computed tomography showed pulmonary infiltration. There was a significant increase in eosinophils in bronchoalveolar lavage fluid. There was no history of residing in a parasite-endemic area or any evidence of parasitic infection. Pathologic examination of bronchoalveolar lavage fluid excluded fungal and mycobacterial infections. The patient was receiving medication for comorbid diseases, but there was no temporal correlation between medication use and clinical manifestations, which excluded drug-induced etiology. Histopathological examination of lung biopsy specimen showed no signs of eosinophilic granulomatosis with polyangiitis, IgG4-related diseases, or tumors. The diagnosis of ABPA was considered based on the history of asthma and the significant increase in serum Aspergillus fumigatus-specific immunoglobulin (Ig)E. Eosinophil-related diseases were excluded through pathological biopsy, which showed typical pathological manifestations of ABPA. CONCLUSION: The possibility of ABPA should be considered in patients with poorly controlled asthma, especially those with eosinophilia, lung infiltration shadows, or bronchiectasis. Screening for serum IgE, Aspergillus fumigatus-specific IgE and IgG, and alveolar lavage can help avoid misdiagnosis.

Severe/critical COVID-19 early warning system based on machine learning algorithms using novel imaging scores.

BACKGROUND: Early identification of severe/critical coronavirus disease 2019 (COVID-19) is crucial for timely treatment and intervention. Chest computed tomography (CT) score has been shown to be a significant factor in the diagnosis and treatment of pneumonia, however, there is currently a lack of effective early warning systems for severe/critical COVID-19 based on dynamic CT evolution. AIM: To develop a severe/critical COVID-19 prediction model using a combination of imaging scores, clinical features, and biomarker levels. METHODS: This study used an improved scoring system to extract and describe the chest CT characteristics of COVID-19 patients. The study also took into consideration the general clinical indicators such as dyspnea, oxygen saturation, alternative lengthening of telomeres (ALT), and androgen suppression treatment (AST), which are commonly associated with severe/critical COVID-19 cases. The study employed lasso regression to evaluate and rank the significance of different disease characteristics. RESULTS: The results showed that blood oxygen saturation, ALT, IL-6/IL-10, combined score, ground glass opacity score, age, crazy paving mode score, qsofa, AST, and overall lung involvement score were key factors in predicting severe/critical COVID-19 cases. The study established a COVID-19 severe/critical early warning system using various machine learning algorithms, including XGBClassifier, Logistic Regression, MLPClassifier, RandomForestClassifier, and AdaBoost Classifier. The study concluded that the prediction model based on the improved CT score and machine learning algorithms is a feasible method for early detection of severe/critical COVID-19 evolution. CONCLUSION: The findings of this study suggest that a prediction model based on improved CT scores and machine learning algorithms is effective in detecting the early warning signals of severe/critical COVID-19.

Association of C-reactive protein and complement factor H gene polymorphisms with risk of lupus nephritis in Chinese population.

BACKGROUND: Complement overactivation is a major driver of lupus nephritis (LN). Impaired interactions of C-reactive protein (CRP) with complement factor H (CFH) have been shown as a pathogenic mechanism that contributes to the overactivation of complement in LN. However, genetic variations of neither CRP nor CFH show consistent influences on the risk of LN. AIM: To examine whether genetic variations of CRP and CFH in combination can improve the risk stratification in Chinese population. METHODS: We genotyped six CRP single nucleotide polymorphisms (SNPs) (rs1205, rs3093062, rs2794521, rs1800947, rs3093077, and rs1130864) and three CFH SNPs (rs482934, rs1061170, and rs1061147) in 270 LN patients and 303 healthy subjects. RESULTS: No linkage was found among CRP and CFH SNPs, indicating lack of genetic interactions between the two genes. Moreover, CRP and CFH SNPs, neither individually nor in combination, are associated with the risk or clinical manifestations of LN. Given the unambiguous pathogenic roles of the two genes. CONCLUSION: These findings suggest that the biological effects of most genetic variations of CRP and CFH on their expressions or activities are not sufficient to influence the disease course of LN.

A high triglyceride-glucose index associated with adverse cardiovascular events in patients with type 2 diabetes mellitus and chronic total occlusion after percutaneous coronary intervention.

Triglyceride-glucose index (TyG index) is a reliable surrogate marker of insulin resistance, associated with morbidity and prognosis of cardiovascular disease. However, its predictive value for cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and chronic total occlusion (CTO) after percutaneous coronary intervention (PCI) has not been studied. Here, we retrospectively enrolled 681 patients with T2DM and CTO after PCI. Patients were divided into two groups based on a median TyG index of 9.02. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The primary observational end point was the composite of overall death, nonfatal myocardial infarction, and unplanned revascularization. The Multivariate Cox hazards regression analysis showed that the TyG index was significantly correlated with the primary end point (hazard ratio = 1.699, 95% confidence interval 1.254-2.303, p = 0.001). The addition of TyG to a baseline risk model had an incremental effect on the predictive value for the primary end point (area under the curve: TyG index vs baseline model, 0.693 vs 0.663, comparison p = 0.040; integrated discrimination improvement = 0.049, p = 0.020). The TyG index might be a predictor of adverse cardiovascular events. Moreover, adding the TyG index into a baseline risk model had a cumulative effect on the predictive potential for the primary end point.

Roxadustat: Do we know all the answers?

Anemia is a common complication of chronic kidney disease (CKD), and its prevalence rises as the disease progresses. Intravenous or subcutaneous erythropoiesis-stimulating agents (ESAs) are advised to treat CKD-associated anemia, since shortage of erythropoietin (EPO) and iron are the main cause of anemia. However, ESA resistance and safety have spurred a lot of interest in the development of alternate anemia therapies. Roxadustat, an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that increases erythropoiesis and may modulate iron metabolism, was recently licensed in China, Chile, South Korea, Japan and the European Union for the treatment of CKD-related anemia. Despite this, clinical trials have shown a number of adverse effects, including cardiovascular disease, hyperkalemia, and infections. In addition, of concern is roxadustat's possible effects on other organs and systems. In this review, based on clinical evidence, we discuss the potentially detrimental effects of roxadustat to the known biology on systems other than kidney, and the need for long-term follow-up in order for roxadustat to be approved in more countries in the future.

[Nutrient uptake strategy selection by first-order roots of Juglans mandshurica under shading and phosphorus limitation]. / 遮阴和磷限制下胡桃楸1çº§æ ¹å »åˆ†å¸æ”¶ç­–ç•¥é€‰æ‹©.

We investigated root growth of 1-year-old Juglans mandshurica seedlings under different light environments and varying doses of phosphorus fertilizer, to understand the relationship between root resource acquisition strategies and the variations of light and phosphorus availability. There were four shading intensities (full light, 65% full light, 35% full light, and 20% full light) along with three doses of phosphate fertilizer (0 (CK), 200% soil background available phosphorus, and 500% soil background available phosphorus). We measured in root morphology characteristics, architectural characteristics, and mycorrhizal colonization rates of first-order roots. The results showed that average diameter, average root length, and mycorrhizal colonization rates of first-order roots gradually decreased, and the specific root length, specific surface area, branching ratio and branching intensity showed a trend of first increasing and then decreasing with the increases of shading degree. As the phosphorus content decreased, the first-order root diameter gradually became thinner, and the mycorrhizal infection rate gradually increased. Root morphology and architecture of J. mandshurica would undergo adaptive changes under shade, adapting to the shading environment by expanding specific root length, specific surface area, branching ratio and branching intensity. Under phosphorus limitation, root system of J. mandshurica would increase phosphorus absorption through symbiosis with mycorrhizal fungi. When J. mandshurica was artificially regenerate in forest land with a light transmittance of 35%, root morphology and architecture would adapt to the shading environment. The symbiosis between J. mandshurica and mycorrhizal fungi would be enhanced under phosphorus limitation, which could improve phosphorus absorption of roots.

[Research Progress in the Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Drugs Targeting Spike Protein].

The coronavirus disease 2019(COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is spreading around the world,while the specific drugs targeting SARS-CoV-2 are still under development.On the basis of the biological characteristics of SARS-CoV-2 and the key protein(spike protein) for viral replication,this paper introduces the research progress in the action sites of related drugs,providing information for clinical application and ideas for development of anti-SARS-CoV-2 drugs.

Serum glycated albumin is associated with in-stent restenosis in patients with acute coronary syndrome after percutaneous coronary intervention with drug-eluting stents: An observational study.

Background: Previous studies have confirmed the predicted value of serum glycated albumin (GA) in atherosclerotic cardiovascular disease. However, the relationship between GA and the development of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation has not been verified in patients with acute coronary syndrome (ACS). Materials and methods: In this study, 797 patients diagnosed with ACS who underwent re-coronary angiography more than 6 months after the first successful DES-based percutaneous coronary intervention (PCI) were eventually included. Patients were categorized into two groups based on the median GA levels of 14.94%. Moreover, multivariate logistic regression analysis models and the net reclassification improvement and integrated differentiation improvement risk models were constructed to assess the relationship between the GA and DES-ISR in patients with ACS. Results: The GA was significantly associated with an increased risk of DES-ISR, upon adjusting for confounding factors (as nominal variate: OR 1.868, 95% CI 1.191-2.932, P = 0.007; as continuous variate: OR 1.109, 95% CI 1.040-1.183, P = 0.002). The addition of GA to a baseline risk model had an incremental effect on the predictive value for DES-ISR (AUC: GA vs. baseline model, 0.714 vs. 0.692, comparison P = 0.017; category-free net reclassification improvement (NRI) 0.080, P = 0.035; integrated discrimination improvement (IDI) 0.023, P < 0.001). Conclusion: GA level was significantly associated with a high risk of DES-ISR in patients with ACS treated with PCI. Moreover, the addition of the GA to a baseline risk model has an incremental effect on the predictive potential for DES-ISR.

Altered regional homogeneity of spontaneous brain activity in patients with toothache: A resting-state functional magnetic resonance imaging study.

Toothache (TA) is a common and severe pain, but its effects on the brain are somewhat unclear. In this study, functional magnetic resonance imaging (fMRI) was used to compare regional homogeneity (ReHo) between TA patients and a normal control group and to explore the brain activity changes during TA, establishing the theoretical basis for the mechanism of neuropathic pain. In total, 20 TA patients and 20 healthy controls (HCs) were recruited and underwent assessment of pain, and then resting-state fMRI (rs-fMRI). The ReHo method was used to analyze the original whole-brain images. Pearson's correlation analysis was used to assess the relationship between mean ReHo values in each brain region and clinical symptoms, and the receiver operating characteristic (ROC) curve was used to conduct correlation analysis on the brain regions studied. The ReHo values of the right lingual gyrus (RLG), right superior occipital gyrus (RSOG), left middle occipital gyrus (LMOG) and right postcentral gyrus (RPG) in the TA group were significantly higher than in HCs. The mean ReHo values in the RLG were positively correlated with the anxiety score (AS) (r = 0.723, p < 0.001), depression score (DS) (r = 0.850, p < 0.001) and visual analogue score (VAS) (r = 0.837, p < 0.001). The mean ReHo values of RSOG were also positively correlated with AS (r = 0.687, p = 0.001), DS (r = 0.661, p = 0.002) and VAS (r = 0.712, p < 0.001). The areas under the ROC curve of specific brain area ReHo values were as follows: RLG, 0.975; RSOG, 0.959; LMOG, 0.975; RPG, 1.000. Various degrees of brain activity changes reflected by ReHo values in different areas of the brain indicate the impact of TA on brain function. These findings may reveal related neural mechanisms underlying TA.

Corrigendum: The cholesterol-binding sequence in monomeric C-reactive protein binds to the SARS-CoV-2 spike receptor-binding domain and blocks interaction with Angiotensin-converting enzyme 2.

[This corrects the article DOI: 10.3389/fimmu.2022.918731.].

Ethical review of off-label drugs during the COVID-19 pandemic.

High-quality scientific research is very important in attempting to effectively control the coronavirus disease 2019 (COVID-19) pandemic and ensure people's health and safety. Chloroquine (CQ) and hydroxychloroquine (HCQ) have received much attention. This article comprehensively investigates the ethical review of off-label CQ and HCQ research during the COVID-19 pandemic with regard to strictly abiding by review standards, improving review efficiency, ensuring the rights and interests of subjects and that ethics committees conduct independent reviews, and achieving full ethics supervision of research conducted during an emergency. Research must be both rigorous and prudent to ensure the best outcome, with the maximization of benefits as the core principle. Standardization of the application, implementation and ethical review processes are needed to prevent unnecessary risk.

Corrigendum: Characteristics of the Fractional Amplitude of Low-Frequency Fluctuation in Ocular Hypertension Patients: A Resting-State fMRI Study.

[This corrects the article DOI: 10.3389/fmed.2021.687420.].

The Cholesterol-Binding Sequence in Monomeric C-Reactive Protein Binds to the SARS-CoV-2 Spike Receptor-Binding Domain and Blocks Interaction With Angiotensin-Converting Enzyme 2.

The receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the human angiotensin-converting enzyme 2 (ACE2) receptor, which is a prerequisite for the virus to enter the cell. C-reactive protein (CRP) is an important marker of inflammation and is a putative soluble pattern recognition receptor. Clinical elevation of CRP levels in patients with COVID-19 is one of the characteristics of the disease; however, whether CRP is involved in COVID-19 pathogenesis is unknown. Here, we report that monomeric CRP (mCRP) can bind to the SARS-CoV-2 spike RBD and competitively inhibit its binding to ACE2. Furthermore, truncated mutant peptide competition assays and surface plasmon resonance binding experiments showed that the cholesterol-binding sequence (CBS, amino acids 35-47) in mCRP was critical for mediating the binding of mCRP to spike RBD. In a cell model of spike RBD and ACE2 interaction, the CBS motif effectively reduced the binding of spike RBD to ACE2 overexpressed on the cell surface. Thus, this study highlights the pattern recognition function of mCRP in innate immunity and provides a preliminary theoretical basis for the development of the CBS motif in mCRP into a functional peptide with both diagnostic significance and potential therapeutic capabilities.

Abnormal Fractional Amplitude of Low Frequency Fluctuation Changes in Patients With Dry Eye Disease: A Functional Magnetic Resonance Imaging Study.

Purpose: To investigate spontaneous brain activity in patients with dry eye (DE) and healthy control (HC) using the fractional amplitude of low frequency fluctuation (fALFF) technique with the aim of elucidating the relationship between the clinical symptoms of DE and changes in brain function. Material and Methods: A total of 28 patients with DE and 28 matched healthy volunteers (10 males and 18 females in each group) were enrolled. Resting-state functional magnetic resonance imaging scans were performed in both groups. Then all subjects were required to complete a comprehensive Hospital Anxiety and Depression Scale (HADS). Receiver operating characteristic (ROC) curve analysis was used to evaluate the differences in fALFF values between the two groups and their diagnostic value. Linear correlations between HADS and fALFF values in different brain regions of DE patients were analyzed using the Pearson correlation coefficient. Results: Patients with DE had significantly higher fALFF values in the left calcarine sulcus (CS) than the HC group, while fALFF values in the bilateral middle frontal gyrus (MFG) and right MFG/right inferior frontal gyrus (IFG) were significantly lower in DE patients than in HC group. fALFF values had a high diagnostic value for differentiating patients with DE from the HC group (P < 0.001). Right MFG and right MFG/IFG were significantly correlated with HADS values. Conclusion: Our study found that DE mainly involved functional disorders in the brain areas of the left CS, bilateral MFG and right MFG/right IFG, which helped us to find possible clinical features of DE disease and reflected the potential pathological mechanism of DE.

Brain Activity in Different Brain Areas of Patients With Dry Eye During the Female Climacteric Period According to Voxel-Based Morphometry.

We aim to investigate potential morphological alterations of the brain in female climacteric patients with dry eye (DE) and their relationship to behavioral performances. Twenty-five female patients with DE disease during the female climacteric period and 25 age and education-matched healthy controls (HCs) underwent magnetic resonance imaging. Imaging data were analyzed using voxel-based morphometry (VBM) to identify group differences in DE patients and HCs. Compared with HCs, patients with DE during the female climacteric period had significantly decreased VBM in the Putamen_L, Thalamus_R, Precuneus_L, Frontal_Sup_R, Cingulum_Mid_L, and Frontal_Mid_L. There was increased VBM in the Temporal_Pole_Sup_R, Precentral_R and Insula_L. Receiver operating characteristic curve analysis indicated that the VBM method has clear potential for diagnosis of DE patients during the climacteric period. Correlation analysis found a negative correlation between the VBM values of the Putamen_L and the anxiety score (AS) and depression score (DS), a positive correlation was found between VBM values of the Temporal_Pole_Sup_R and AS. Moreover, VBM values in the Cingulum_Mid_L were positively correlated with AS and DS. These results revealed abnormal spontaneous activity in the brain regions of patients with DE during the climacteric period, which may indicate underlying pathological mechanisms. These results may help to advance clinical treatments.

Nardosinone regulates the slc38a2 gene to alleviate Parkinson's symptoms in rats through the GABAergic synaptic and cAMP pathways.

In a rotenone-induced Parkinson's disease (PD) rat model, behavioral investigation, pathological examination, inflammatory factor analysis, and mitochondrial structure and function investigation verified the anti-PD efficacy of nardosinone. A combined transcriptome and proteome analysis proposed that the anti-PD target of nardosinone is the slc38a2 gene and may involve the GABAergic synaptic pathway and cAMP-signaling pathway. Analysis of targeted slc38a2 knockout cells and expression of key enzyme-encoding genes in both pathways verified the target and pathways proposed by the 'omics analysis. This further confirms that nardosinone can regulate the slc38a2 gene, a potential new target for the treatment of Parkinson's disease, and plays an anti-PD role through the GABAergic synaptic and cAMP pathways.

Altered Brain Activity in Strabismic Amblyopic Children as Determined by Regional Homogeneity: A Resting-State Functional Magnetic Resonance Imaging Study.

Objective: Earlier research has determined that amblyopia or strabismus may cause remarkable brain anatomical and functional variations. Nonetheless, thus far, the spontaneous changes in brain activity in children with strabismus amblyopia (SA) remain unclear. The purpose of this study was to determine the association between abnormal brain activity in children with SA and its behavioral manifestations. Patients and Methods: ?A total of 24 children with SA (10 male and 14 female children) as well as 24 healthy controls (HCs), including 10 male and 14 female children were closely matched in sex and age, and examined using resting-state functional magnetic resonance imaging (fMRI). The regional homogeneity (ReHo) technique was applied to evaluate spontaneous cerebral activity variations in children with SA and HCs. Moreover, associations between altered ReHo values in distinct cerebral areas and the degree of strabismus were assessed using Pearson correlation analysis. Results: Remarkably increased ReHo values were observed in the right lingual, right superior frontal medial, bilateral superior parietal, and right inferior parietal gyri of children with SA compared with HCs. In contrast, mean ReHo values in children with SA were lower in the right cerebellum, left superior frontal gyrus, and left putamen nucleus. Furthermore, esotropia showed a positive correlation with ReHo values of the left putamen. Conclusion: The anomalous spontaneous activity changes in several brain areas that are caused by SA may indicate neuropathologic mechanisms of visual deficits and oculomotor disorders in children with SA.

Neuron-Specific Enolase and Hemoglobin as Risk Factors of Intraocular Metastasis in Patients with Renal Cell Carcinoma.

Renal cell carcinoma (RCC) appears to be a high risk of spread. This research investigated the correlation between a different range of clinical features and intraocular metastasis (IOM) in RCC patients and attempted to determine potential risk factors of RCC patients with IOM. In the study, there are a total of 351 patients with RCC that were recruited between May 1994 and May 2016. The differences between RCC patients with IOM and RCC patients with non-IOM (NIOM) were evaluated by the chi-squared test and Student t test. Binary logistic regression analysis was applied to determine risk factors. Finally, the value of diagnosis for RCC patients with IOM was assessed by receiver operating characteristic (ROC) curve analysis. Eighteen individuals were identified with IOM. There were no significant differences that were detected in alkaline phosphatase (AFP), carcinoembryonic antigen (CEA), alkaline phosphatase (ALP), cancer antigen 125 (CA-125), cancer antigen 153 (CA-153), cancer antigen 199 (CA-199), calcium, age, primary tumor site, and histopathological subtypes between the two groups. But there was a difference in terms of gender (P < 0.05). The IOM group exhibited significantly higher neuron-specific enolase (NSE) and lower hemoglobin (Hb) values compared to the NIOM group (P < 0.05, respectively). Binary logistic regression identified NSE and Hb as significant risk factors of IOM for RCC patient (P < 0.05 and P < 0.001, respectively). The ROC curve analysis indicated that the area under the curve (AUC) values of NSE and Hb were 0.694 and 0.749, while cut-off values were 49.5 ng/mL and 102.5 g/L, respectively. The sensitivity and specificity of NSE were 72.2% and 66.4%, respectively, while those of Hb were 72.2% and 74.2%, respectively. The result reveals that NSE and Hb represent promising significant risk factors of IOM for RCC patients. Notably, Hb is more reliable than NSE in distinguishing case of IOM from NIOM in patients with RCC.