Alterations of resting-state network dynamics in Alzheimer's disease based on leading eigenvector dynamics analysis.

Alzheimer's disease (AD) is a neurodegenerative disease, and mild cognitive impairment (MCI) is considered a transitional stage between healthy aging and dementia. Early detection of MCI can help slow down the progression of AD. At present, there are few studies exploring the characteristics of abnormal dynamic brain activity in AD. This article uses a method called Leading Eigenvector Dynamics Analysis (LEiDA) to study resting-state functional magnetic resonance imaging (rs-fMRI) data of AD, MCI, and cognitively normal (CN) participants. By identifying repetitive states of phase coherence, inter group differences in brain dynamic activity indicators are examined. And the neurobehavioral scales were used to assess the relationship between abnormal dynamic activities and cognitive function. The results showed that in the indicators of occurrence probability and lifetime, the globally synchronized state of the patient group decreased. The activity state of the limbic regions significantly detected the difference between AD and the other two groups. Compared to CN, AD and MCI have varying degrees of increase in default and visual regions activity states. In addition, in the analysis related to the cognitive scales, it was found that individuals with poorer cognitive abilities were less active in the globally synchronized state, and more active in limbic regions activity state and visual regions activity state. Taken together, these findings reveal abnormal dynamic activity of resting-state networks in patients with AD and MCI, provide new insights into the dynamic analysis of brain networks, and contribute to a deeper understanding of abnormal spatial dynamic patterns in AD patients.

[Clinical Characteristics and Prognosis of Patients with Acute Leukemia Complicated with Mucormycosis after Chemotherapy].

OBJECTIVE: To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia, and to strengthen understanding of the disease. METHODS: 7 cases of acute leukemia (AL) patients diagnosed with mucormycosis by metagenomic next generation sequencing (mNGS) after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected, and their clinical data, including clinical characteristics, diagnosis, treatment, and prognosis, were retrospectively analyzed. RESULTS: Among the 7 patients with AL complicated with mucormycosis, there were 3 males and 4 females, with a median age of 52(20-59) years. There were 6 cases of acute myeloid leukemia (AML) and 1 case of acute lymphocytic leukemia (ALL). Extrapulmonary involvement in 4 cases, including 1 case suspected of central nervous system involvement. The median time for the occurrence of mucor infection was 16(6-69) days after chemotherapy and 19(14-154) days after agranulocytosis. The main clinical manifestations of mucormycosis were fever (7/7), cough (3/7), chest pain (3/7) and dyspnea (1/7). The most common chest CT imaging findings were nodules, patchy or mass consolidation (6/7). All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase. 5 patients died within 8 months, and the median time from diagnosis to death was 1 month. CONCLUSION: Although prophylactic antifungal therapy is adopted, patients with acute leukemia still have a risk of mucor infection during the neutropenia phase. Fever is the main manifestation in the early stage of mucor infection. The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

[The Distribution and Significance of Activated T Cells and Lymphocyte Subsets in Myelodysplastic Syndrome].

OBJECTIVE: To investigate the distribution of bone marrow lymphocyte subsets in patients with myelodysplastic syndrome(MDS),the proportion of activated T cells with immunophenotype CD3+HLA-DR+ in the lymphocytes and its clinical significance, and to understand the effects of different types of MDS, different immunophenotypes, and different expression levels of WT1 on the proportion of lymphocyte subsets and activated T cells. METHODS: The immunophenotypes of 96 MDS patients, the subsets of bone marrow lymphocytes and activated T cells were detected by flow cytometry. The relative expression of WT1 was detected by real-time fluorescent quantitative PCR, and the first induced remission rate (CR1) was calculated, the differences of lymphocyte subsets and activated T cells in MDS patients with different immunophenotype, different WT1 expression, and different course of disease were analyzed. RESULTS: The percentage of CD4+T lymphocyte in MDS-EB-2, IPSS high-risk, CD34+ cells >10%, and patients with CD34+CD7+ cell population and WT1 gene overexpression at intial diagnosis decreased significantly (P<0.05), and the percentage of NK cells and activated T cells increased significantly (P<0.05), but there was no significant difference in the ratio of B lymphocytes. Compared with the normal control group, the percentage of NK cells and activated T cells in IPSS-intermediate-2 group was significantly higher(P<0.05), but there was no significant difference in the percentage of CD3+T, CD4+T lymphocytes. The percentage of CD4+T cells in patients with complete remission after the first chemotherapy was significantly higher than in patients with incomplete remission(P<0.05), and the percentage of NK cells and activated T cells was significantly lower than that in patients with incomplete remission (P<0.05). CONCLUSION: In MDS patients, the proportion of CD3+T and CD4+T lymphocytes decreased, and the proportion of activated T cells increased, indicating that the differentiation type of MDS is more primitive and the prognosis is worse.

[Research Progress on the Role of Tumor-Associated Macrophages in Multiple Myeloma --Review].

Bone marrow microenvironment is a highly complex environment surrounding tumor, which plays an important role in the survival, proliferation, drug resistance and migration of multiple myeloma (MM) cells. As an important cellular component in tumor microenvironment, tumor-associated macrophages(TAM) has attracted attention due to its key role in tumor progression and drug resistance. Targeting TAM has shown potential therapeutic value in cancer treatment. In order to clarify the role of macrophages in MM progression, it is necessary to understand the differentiation of TAM and its characteristics of promoting MM. This paper reviews the research progress on how TAM is programmed in MM and the mechanism of TAM promoting tumor development and drug resistance.

A multifunctional cobalt-organic framework for proton conduction and selective sensing of Fe3+ ions.

Developing multifunctional metal-organic frameworks (MOFs) is a new research trend. MOFs have shown remarkable performances in both proton conduction and fluorescence sensing, but the MOFs integrating the two performances are scarce. Herein, a Co-MOF, [Co6(oba)4(Hatz)(atz)(H2O)2(µ3-OH)2(µ2-OH)]·H2O (1, H2oba = 4,4-oxybis(benzoic acid), Hatz = 5-amino-1H tetrazole), has been assembled by Co2+ ions with H2oba and Hatz ligands, providing a unique example of multifunctional MOFs with both proton conduction and fluorescence sensing performances. The framework of 1 displays a pillar-layer structure built by the oba ligand as a pillar and a layer composed of Co-clusters and atz linkers. Because large-scale single crystals of 1 were successfully synthesized, the proton conduction ability of 1 was investigated using single crystal samples. 1 exhibits highly anisotropic conduction with conductivity values of 1.1 × 10-3 S cm-1 along the [001] direction and 9.1 × 10-6 S cm-1 along the [010] direction at 55 °C and 95% RH, respectively. Meanwhile, the fluorescence sensing of 1 towards metal ions was studied in aqueous solutions. Attractively, 1 may sensitively and selectively detect Fe3+ ions in the presence of other interfering ions by fluorescence quenching.

[Clinical Application and Research Progress of Circulating Tumor DNA in Diffuse Large B-Cell Lymphoma--Review].

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, its diagnosis and prognosis evaluation mainly depends on tissue biopsy and imaging examination. As a part of liquid biopsy, circulating tumor DNA (ctDNA) is a novel noninvasive and real-time tumor-specific biomarker, which can reliably reflect the comprehensive tumor genetic profiles, and it plays an important role in assisting early diagnosis, monitoring the curative effect, prognosis evaluation and prediction of recurrence of DLBCL. This review summarized recent research progress of ctDNA in DLBCL.

Development and validation of a novel model based on hand knob score and white matter injury on MRI to predict hand function in children with cerebral palsy.

Background: Childhood hand function is considered to be one of the strongest predictors of the ability to participate in daily activities as children with cerebral palsy (CP) reach adulthood. The manual ability classification system (MACS) is currently the most widely used for grading hand function in children with CP. However, the MACS method is subjective and may be affected by the raters' experience. Hand knob is an important control center for hand movement. Therefor this study aimed to develop and validate an objective model for hand function estimation in children with CP and visualize it as a nomogram. Methods: A total of 70 Children (2-12 years old) with CP underwent magnetic resonance imaging (MRI) scanning, MACS assessment. According to MACS, children with CP were divided into mild impairment group (grade I-III) and severe impairment group (grade IV-V). Hand function prediction models based on (I) hand knob score, (II) clinical features, and (III) the combination of clinical features and hand knob score were developed and validated separately. The models were subjected to stepwise regression according to the maximum likelihood method, and the Akaike information criterion was used to select the best model. Model discrimination was assessed using receiver operating characteristic (ROC) and calibration curves. The nomogram was finally built according to the best model. Results: The area under the curve (AUC) of the hand knob score model in the training set was 0.752, the clinical features model was 0.819, and the hand knob score and clinical features combined model was 0.880. The AUC of the hand knob score model in the validation set was 0.765, the clinical features model was 0.782, and the combined model was 0.894. The best model was the hand knob score-clinical features combined model, and the nomogram finally incorporated two assessment items: the hand knob score and white matter injury. The estimated probability of hand function injury degree of the combined model displayed good agreement with the actual occurrence probability. Conclusions: The hand knob score-clinical features combined model can be used to preliminarily assess the degree of hand impairment in children with CP, with good calibration.

Decomposition-Reassembly Synthesis of a Silverton-Type Polyoxometalate 3D Framework: Semiconducting Properties and Photocatalytic Applications.

Polyoxometalate-based all-inorganic three-dimensional (3D) frameworks have recently attracted attention as a unique class of materials due to their unique physicochemical properties and a wide field of application with excellent prospects. We herein synthesized a novel all-inorganic 3D framework material based on cobalt-substituted Silverton-type polyoxometalate, H6{Co6W10O42[Co(H2O)4]3}·2H2O (Co9W10), which was successfully constructed using Na12[WCo3II(H2O)2(CoIIW9O34)2]·46-48H2O (Co5W19) and Co(NO3)2·6H2O as starting materials in a hydrothermal reaction via a decomposition-reassembly route together with the rational adjustment of pH values. Co9W10 has been structurally characterized using single-crystal X-ray diffraction. Photocurrent response, band-gap (Eg) value, and the VB-XPS spectrum have been measured to reveal the semiconducting property of Co9W10. Furthermore, we synthesized x% PTh/Co9W10 composites (PTh = polythiophene, x = 0.5, 1, 2, 5) for photodegradation of tetracycline hydrochloride (TH) to evaluate the photocatalytic activities of title composites. Due to the optimal molar ratio of hybrids and matching energy levels, 2% PTh/Co9W10 composites show the best photocatalytic activities among these composites.

Matrine exerted an anti-tumor effect on acute myeloid leukemia via the lncRNA LINC01116/miR-592-mediated JAK/STAT pathway inactivation.

As a malignant hematological cancer, acute myeloid leukemia (AML) influences the health of many people. This study explored the anti-AML activity of matrine (a natural-derived alkaloid), as well as the internal molecular mechanism. In vitro, cell viability, apoptosis, and productions of inflammatory cytokines including IL-1ß, IL-6, and TNF-α were tested by MTT, Annexin V-FITC/PI staining, and ELISA, respectively. The expression levels of LINC01116 and miR-592 were measured by qRT-PCR. Bcl-2 and PCNA expression, and JAK/STAT3 pathway activity were evaluated by western blotting. Besides, an AML mouse xenograft model was established to further analyze the anti-AML activity of matrine. We found that matrine suppressed cell proliferation and levels of inflammatory factors, induced cell apoptosis, reduced LINC01116 expression, and raised miR-592 expression in AML cells. LINC01116 directly bound to miR-592 and downregulated its expression. Both LINC01116 overexpression and miR-592 knockdown attenuated the effects of matrine on AML cells. Moreover, miR-592 overexpression reversed the influences of LINC01116 overexpression on matrine-treated AML cells. Matrine inactivated the JAK/STAT3 pathway in AML cells via modulating LINC01116/miR-592. Additionally, matrine inhibited tumor growth via modulating LINC01116/miR-592 in vivo. To sum up, matrine exhibited the anti-AML activity through regulating the LINC01116/miR-592 axis, thereby inactivating the JAK/STAT3 pathway.

Adverse Effects Associated With Currently Commonly Used Antifungal Agents: A Network Meta-Analysis and Systematic Review.

Background: Invasive fungal infections (IFI) is an important contributing factor in morbidity and mortality of immunocompromised and critically ill patients. Although the therapeutic effects of these drugs on IFI have been well documented, the long-term use of antifungal agents has raised concerns about drug tolerability and treatment-related toxicity risks. Methods: We searched articles published before June 30, 2020 in four electronic databases: Web of Science, Cochrane Library, embase and PubMed. Results: 66 trials were determined to meet our inclusion criteria, providing data on 18,230 participants. We sorted out 23 AEs by system organ classes and six laboratory AEs, 13 of these were used to construct 13 network meta-analyses. Compared with LAmB, anidulafungin, caspofungin, micafungin, fluconazole, and posaconazole had a significantly low incidence of discontinuation of therapy due to AEs (OR = 0.24 (0.09,0.65), 0.24 (0.13,0.43), 0.32 (0.19,0.52), 0.38 (0.23,0.62) and 0.35 (0.17,0.69), respectively). Conclusion: We found that echinocandins are the most tolerated antifungal agents with high safety. The AEs of triazole drugs are mainly concentrated on the increase in liver enzymes, nervous system disorders, especially visual disorders, gastrointestinal disorders, and cardiac diseases. LAmB is the least tolerated and has the most abundant AEs.

pH-Controlled assembly of [ZnW12O40]6--based hybrids from a 0D dimer to a 2D network: synthesis, crystal structure, and photocatalytic performance in transformation of toluene into benzaldehyde.

Polyoxometalate-based organic-inorganic hybrids have attracted considerable attention due to their fascinating structures and wide application prospects. In this work, using the same building blocks, ligands and metal ions (ZnW12O406-(ZnW12), 2,2'-bipyridine (2,2'-bipy), and Cu2+), we synthesized three new POM-based hybrids by controlling the pH values of the reaction systems. These three compounds {(Zn0.6(H2)0.4W12O40)[Cu(2,2'-bipy)(H2O)][Cu(2,2'-bipy)(H2O)2][Cu(2,2'-bipy)(H2O)3]}2·6H2O (1), (Me4N)2{ZnW12O40[Cu(2,2'-bipy)(H2O)][Cu(2,2'-bipy)(H2O)3]}·5H2O (2), and {(Zn0.5(H2)0.5W12O40)[Cu(2,2'-bipy)][Cu(2,2'-bipy)(H2O)][Cu(2,2'-bipy)(H2O)2]}·5H2O (3) have been structurally characterized by single-crystal X-ray diffraction. Compound 1 appears as a dimeric cluster structure, while compounds 2 and 3 appear as a 1D chain structure and a 2D network, respectively. The semiconducting properties of compounds 1-3 are different, which was demonstrated by band gap (Eg) and photocurrent response measurements. Compound 3 can efficiently catalyze the photooxidation of toluene to benzaldehyde with high selectivity using molecular oxygen as the oxidant component. Moreover, compound 3 was recycled and reused three times without significant degradation in conversion and selectivity. In addition, the mechanism of the photocatalytic reaction was also investigated.

Systemic lupus erythematosus complicated with reversible posterior encephalopathy syndrome: a case report.

A 28-year-old female patient was hospitalized primarily because of "intermittent fever for 28 days aggravated by systemic rashes, oral ulcer, and edema in both eyelids for 5 days." During treatment, convulsions and loss of consciousness occurred. Magnetic resonance imaging (MRI) of the head revealed an abnormal signal with shadows in the bilateral frontal, parietal, temporal, and occipital lobes; cerebellar hemispheres; and basal nodes, with high signal intensity on T2 weighted imaging (T2WI), on fluid-attenuated inversion-recovery, and of the apparent diffusion coefficient and low signal intensity on T1WI and diffusion weighted imaging. Therefore, the patient was diagnosed with systemic lupus erythematosus (SLE) with reversible posterior encephalopathy syndrome (RPES). Intravenous high-dose methylprednisolone and cyclophosphamide were administered for blood pressure control, which effectively controlled the disease. Therefore, when patients with SLE and hypertension or renal insufficiency or those receiving high-dose methylprednisolone or immunosuppressants suddenly present with neurologic abnormalities, a diagnosis of RPES must be considered, and head MRI is the first choice for diagnosis of this disease. In terms of treatment, the blood pressure should be quickly controlled, and the primary disease should be aggressively treated.

Blood eosinophil count-guided corticosteroid therapy and as a prognostic biomarker of exacerbations of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and dyspnea, as well as an increase in the number of leukocytes in the airways, lungs, and pulmonary vessels. A 'One size fits all' approach to COPD patients with different clinical features may be considered outdated. The following are the two major objectives of this meta-analysis: the first is to determine if blood eosinophil counts (BEC) can serve as a prognostic biomarker of COPD outcomes, and the second is to determine which level of BEC is effective for inhaled corticosteroid (ICS) treatment. METHODS: We searched articles published before 15 May 2021 in the following four electronic databases: Web of Science, Cochrane Library, EMBASE, and PubMed. RESULTS: A total of 42 studies, comprising a sampling of 188,710 subjects, were summarized and compared in this meta-analysis. The rate ratio (RR) of exacerbations of COPD (ECOPD) between ICS and non-ICS treatment was statistically significant for the COPD patients with a baseline BEC ⩾ 2% or ⩾ 200 cells/µl, RR = 0.82 (0.73, 0.93) or 0.79 (0.70, 0.89) respectively, while the RR of ECOPD between ICS and non-ICS treatment was statistically insignificant for the COPD patients with baseline BEC < 2% or <200 cells/µl, RR = 0.97 (0.87, 1.08) or 0.97 (0.86, 1.08), suggested that ICS therapy was beneficial to the improvement of ECOPD in patients with a baseline BEC ⩾ 2% or BEC ⩾ 200 cells/µl. CONCLUSION: Our research shows that a BEC ⩾ 200 cells/µl or ⩾2% is likely to become the cutoff value of ICS treatment for ECOPD. Moreover, we believe that the baseline BEC can be used as a biomarker for predicting ECOPD. The stability of BEC requires special attention.

Discovery of novel tubulin inhibitors targeting taxanes site by virtual screening, molecular dynamic simulation, and biological evaluation.

Microtubules play crucial role in process of mitosis and cell proliferation, which have been considered as attractive drug targets for anticancer therapy. The aim of this study was to discover novel and chemically diverse tubulin inhibitors for treatment of cancer. In this investigation, the multilayer virtual screening methods, including common feature pharmacophore model, structure-based pharmacophore model and molecular docking, were developed to screen BioDiversity database with 30,000 compounds. A total of 102 compounds were obtained by the virtual screening, and further filtered by diverse chemical clusters with desired properties and PAINS analysis. Finally, 50 compounds were selected and submitted to the biological evaluation. Among these hits, hits 8 and 30 with novel scaffolds displayed stronger antiproliferative activity on four human tumor cells including Hela, A549, MCF-7, and HepG2. Moreover, the two hits were subsequently submitted to molecular dynamic simulations of 90 ns with the aim of exploring the stability of ligand-protein interactions into the binding pocket, and further probing the mechanism of the interaction between tubulin and hits. The molecular dynamic simulation results revealed there had stronger interactions between tubulin and hits in equilibrium state. Therefore, the hits 8 and 30 have been well characterized as lead compounds for developing new tubulin inhibitors with potential anticancer activity.

Positive reverse transcription-polymerase chain reaction assay results in patients recovered from COVID-19: Report of two cases.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread around the globe. On February 28, 2020, the World Health Organization adjusted the risk of spread and impact of COVID-19 to "very high" at the global level. Studies have mainly focused on the etiology, epidemiology, and treatment of COVID-19 to limit further spread and the negative impact of the disease, while less attention has been devoted to the follow-up and reexamination of patients who recovered from COVID-19 or were released from quarantine. CASE SUMMARY: This study reports two cases where patients who had negative reverse transcription-polymerase chain reaction (RT-PCR) test results and met the criteria for discharge subsequently had positive RT-PCR test results. The clinical manifestations and computed tomography (CT) findings of these patients were examined. The conversion of RT-PCR test results in these two patients may be related to false-negative and false-positive outcomes of the test. CT images helped track improvement of pulmonary lesions. CONCLUSION: The timing of discharge of COVID-19 patients should be determined by comprehensive analysis of CT images and RT-PCR test results.

Collagen type VIII alpha 2 chain (COL8A2), an important component of the basement membrane of the corneal endothelium, facilitates the malignant development of glioblastoma cells via inducing EMT.

Glioblastoma (GBM) is one of the most lethal tumor of all human cancers. Due to its poor response to chemotherapy and radiotherapy as well as its high rate of recurrence after treatment, the treatment is still undesired. The identification of potential related genes and bio-markers in the development of GBM could provide some new targets for the treatment of GBM. Our purpose in this study was to evaluate the mission of COL8A2 in GBM. Combined with TCGA, Oncomine databases, CGGA, GEPIA website and qRT-PCR analyses, we found that COL8A2 was up-regulated both in GBM tissues and cells compared to the controls. Moreover, the high COL8A2 expression was associated with the shorter overall survival of patients with GBM. The expression of COL8A2 was also positively correlated with metastasis-associated genes including vimentin, snail, slug, MMP2 and MMP7 according to GEPIA website. Knockdown of COL8A2 could suppress the cell proliferation, cell migration and invasion, whereas the overexpression of COL8A2 significantly expedited these processes. What's more, the outcome of western blot analysis manifested that COL8A2 could induced the expression of vimentin, snail, slug, MMP2 and MMP7. Taken together, COL8A2 activated cell proliferation, cell migration and invasion via raising the relative expression of EMT-related proteins in GBM. Therefore, our investigation suggests the oncogenic role of COL8A2 in GBM and provides a potential application of COL8A2 for GBM therapy.