Two- and 3-year outcomes in convalescent individuals with COVID-19: A prospective cohort study.

As the long-term consequences of coronavirus disease 2019 (COVID-19) have not been defined, it is necessary to explore persistent symptoms, long-term respiratory impairment, and impact on quality of life over time in COVID-19 survivors. In this prospective cohort study, convalescent individuals diagnosed with COVID-19 were followed-up 2 and 3 years after discharge from hospital. Participants completed an in-person interview to assess persistent symptoms and underwent blood tests, pulmonary function tests, chest high-resolution computed tomography, and the 6-min walking test. There were 762 patients at the 2-year follow-up and 613 patients at the 3-year follow-up. The mean age was 60 years and 415 (54.5%) were men. At 3 years, 39.80% of the participants had at least one symptom; most frequently, fatigue, difficulty sleeping, joint pain, shortness of breath, muscle aches, and cough. The participants experienced different degrees of pulmonary function impairment, with decreased carbon monoxide diffusion capacity being the main feature; results remained relatively stable over the 2-3 years. Multiple logistic regression analysis demonstrated that female sex and smoking were independently associated with impaired diffusion capacity. A subgroup analysis based on disease severity was performed, indicating that there was no difference in other parameters of lung function except forced vital capacity at 3-year follow-up. Persistent radiographic abnormalities, most commonly fibrotic-like changes, were observed at both timepoints. At 3 years, patients had a significantly improved Mental Component Score compared with that at 2 years, with a lower percentage with anxiety. Our study indicated that symptoms and pulmonary abnormalities persisted in COVID-19 survivors at 3 years. Further studies are warranted to explore the long-term effects of COVID-19 and develop appropriate rehabilitation strategies.

Epstein-Barr virus infection with non-tumor-associated Anti-N-Methyl-D-Aspartate receptor encephalitis: a case report and review of literature.

To study a case of a middle-aged male with a non-tumor-associated Epstein-Barr virus (EBV) infection associated with Anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), to explore the role of EBV in the pathogenesis of anti-NMDARE. The patient was diagnosed with "Anti-NMDARE, EBV infection" by using Cerebrospinal fluid (CSF) autoimmune encephalitis profile, and Metagenomics Next-Generation Sequencing (mNGS) pathogenic microbial assays, we discuss the relationship between EBV and NMDARE by reviewed literature. EBV infection may trigger and enhance anti-NMDARE, and the higher the titer of NMDAR antibody, the more severe the clinical presentation.

A common variant SNP rs1937810 in the MPP7 gene contributes to the susceptibility of breast cancer in the Chinese Han population.

BACKGROUND: Breast cancer (BC) is common cancer caused by environmental factors and genetic ones. Previous evidence has linked gene MAGUK P55 Scaffold Protein 7 (MPP7) to BC, despite that there has been no research evaluating the relationship between MPP7 genetic polymorphisms and BC susceptibility. We aimed to investigate the potential association of the MPP7 gene with the susceptibility to BC in Han Chinese individuals. METHODS: In total, 1390 patients with BC and 2480 controls were enrolled. For genotyping, 20 tag SNPs were chosen. The serum levels of protein MPP7 were measured in all subjects using an enzyme-linked immunosorbent assay. Genetic association analysis was performed in both genotypic and allelic modes, and the relationship between BC patients' clinical features and genotypes of relevant SNPs was examined. The functional implications of significant markers were also evaluated. RESULTS: After adjusting for Bonferroni correction, SNP rs1937810 was found to be significantly associated with the risk of BC (p = 1.19 × 10-4 ). The odds ratio of CC genotypes in BC patients was 49% higher than in controls (1.49 [1.23-1.81]). Serum MPP7 protein levels were significantly higher in BC patients than in controls (p < 0.001). The protein level of the CC genotype was the highest, and that of the CT and TT genotypes decreased in turn (both p < 0.001). CONCLUSIONS: Our results linked SNP rs1937810 to the susceptibility of BC and the clinical features of BC patients. This SNP is also proved to be significantly related to the serum level of protein MPP7 in both BC patients and controls.

Incidence and Predictive Model of Medical Adhesive-Related Skin Injury in Cancer Patients Managed With Central Venous Access Devices: A Retrospective Study.

PURPOSE: The purpose of this study was to determine the prevalence of medical adhesive-related skin injury (MARSI) at the site of central venous access device (CVAD) implantation in patients with cancer, identify risk factors associated with MARSI in patients with cancer, and create a nomogram for predicting risk of MARSI. DESIGN: Retrospective, single-center study. SUBJECTS AND SETTING: The sample comprised 1172 consecutive patients who underwent CVAD implantation between February 2018 and February 2019; their mean age was 55.7 years (SD: 13.9). Data were collected at the First Affiliated Hospital of Xi'an Jiaotong University, located in Xi'an, China. METHODS: Demographic and pertinent clinical data were collected from patient records. Routine dressing changes were performed every 7 days for peripherally inserted central venous catheters (PICCs) or 28 days for ports except in patients with existing skin injuries. Skin injuries related to use of medical adhesives and persisting for more than for 30 minutes were classified MARSI. Data were used to develop a nomogram for predicting MARSI. The accuracy of the nomogram was verified by calculating the concordance index (C-index) and drawing a calibration curve. RESULTS: Among the 1172 patients, 330 (28.2%) had undergone PICC implantation, and 282 (24.1%) experienced 1 or more MARSIs representing an incidence rate of 1.7 events per 1000 CVAD days. Statistical analysis identified previous MARSI history, the need for total parenteral nutrition support, other catheter-related complications, a history of allergy, and PICC implantation as associated with a higher likelihood of developing for MARSI. Based on these factors, we established a nomogram for predicting the risk of developing MARSI in patients with cancer who underwent CVAD implantation. The C-index of the nomogram was 0.96, and the calibration curve of the nomogram showed that the predictive ability of the nomogram was strong. CONCLUSIONS: We evaluated patients with cancer who were undergoing CVAD and identified that previous MARSI history, patients needing total parenteral nutrition support, other catheter-related complications, allergic history, and PICC implantation (compared with ports) were associated with a higher likelihood for developing MARSI. The nomogram we developed showed a good ability for predicting the risk of developing MARSI and may assist nurses to predict MARSI in this population.

Revealing the effect of Nb5+ on the electrochemical performance of nickel-rich layered LiNi0.83Co0.11Mn0.06O2 oxide cathode for lithium-ion batteries.

The layered Nb5+-doped LiNi0.83Co0.11Mn0.06O2 (NCM) oxide cathode materials are successfully synthesized through introducing Nb2O5 into the precursor Ni0.83Co0.11Mn0.06(OH)2 during the lithiation process. The results refined by GSAS software present that the Nb5+-doped samples possess the perfect crystal structure with broader Li+ diffusion pathways. Moreover, the morphology characterized by scanning electron microscope displays the compact secondary particles packed by smaller primary particles under the effect of Nb5+. The excellent electrochemical properties are also acquired from the Nb5+-doped samples, in which the optimal rate performance and cycling stability are performed for NCM-1.0 when up to 1.0 mol % of Nb2O5 (based on the precursor) is added. Benefited from the introduction of Nb5+, the cell assembled with the NCM-1.0 electrode retains higher capacity retention of 86.6 % at 1.0 C and 25 °C, and 71.7 % at 1.0 C and 60 °C after 200cycles. Moreover, it also delivers higher discharge specific capacity of 154.6 mAh g-1 at 5.0 C. Therefore, the Nb5+-doping strategy may open an effective route for optimizing nickel-rich oxide cathode materials, which is worth popularizing for the enhancement of the electrochemical performance of nickel-rich cathodes for lithium-ion batteries.

The roles of gold and silver nanoparticles on ZnIn2S4/silver (gold)/tetra(4-carboxyphenyl)porphyrin iron(III) chloride hybrids in carbon dioxide photoreduction.

The construction of hybrid catalysts composed of inorganic semiconductors and molecular catalysts shows great potential for achieving high photocatalytic carbon dioxide (CO2) conversion efficiency. In this study, ZnIn2S4 was first synthesized via a solvothermal route. Gold (Au) and silver (Ag) nanoparticles were then deposited on ZnIn2S4 via the reduction of noble metal precursor by sulfur vacancy defects. The obtained composite was further combined with tetra(4-carboxyphenyl)porphyrin iron(III) chloride (FeTCPP) molecular catalyst for efficient photocatalytic CO2 conversion. The roles of different noble metal nanoparticles in charge separation and interfacial electron transfer have been comprehensively studied. The photocatalytic performance and photoelectrochemical characterizations demonstrate that the introduction of Ag or Au nanoparticles is beneficial for charge separation. More importantly, the presence of Ag nanoparticles plays a crucial role in promoting the interfacial charge transfer between ZnIn2S4 and FeTCPP, whereas, Au nanoparticles function as active sites for the water reduction reaction.

Single-Cell Sequencing of Immune Cell Heterogeneity in IgG4-Related Disease.

Background: The IgG4-related disease (IgG4-RD) is an immune-mediated disorder with fibrotic manifestations. However, the transcriptional profiles of immune cell subsets at single-cell level are unknown. Herein, single-cell sequencing was used to assess the specific cell subpopulations and pathways in peripheral blood mononuclear cells (PBMCs) of IgG4-RD. Methods: Single-cell sequencing was performed using the PBMCs from four patients with IgG4-RD and three healthy controls (HCs). Functional enrichment and cell analysis were performed through re-clustering of PBMCs to assess functional pathways and intercellular communication networks in IgG4-RD. Western blot and flow cytometry were used to verify sequencing and functional enrichment results. Results: Four major cell types and 21 subtypes were identified. Further subclustering demonstrated that plasma B-cell proportions increased with increasing glycolysis/gluconeogenesis activity in IgG4-RD. Re-clustering of myeloid cells showed that EGR1 and CD36 expressions were significantly increased in CD14+ monocytes of IgG4-RD, as validated by Western blot analysis. Moreover, tumor necrosis factor (TNF) production pathways were positively regulated in CD14+ monocytes of IgG4-RD. In vitro stimulation showed that CD14+ monocytes of IgG4-RD could secrete higher levels of TNF-α . Notably, the proportions of CD8 central memory T (TCM) and TIGIT+ CD8 cytotoxic T (CTL) increased in patients with IgG4-RD compared with HCs. Further interaction analysis showed that B cell activation factor (BAFF) signaling pathways were enriched from myeloid cells subsets to B cells. Conclusion: This study enhances the understanding of the cellular heterogeneity and transcriptional features involved in the pathogenesis of IgG4-RD, providing key clinical implications.

Expanded CD4+CXCR5-PD-1+ peripheral T helper like cells and clinical significance in IgG4-related disease.

To identify the phenotypic features and clinical significance of peripheral T helper (Tph) like cells in IgG4-RD, 54 untreated IgG4-RD patients and 57 healthy controls (HCs) were enrolled. Flow cytometry analysis, ELISA and correlation analysis were performed. Results indicated that percentages of CD4 + CXCR5-PD-1+ Tph like cells in the peripheral blood of IgG4-RD patients were significantly higher than those of HCs (2.27% ± 1.99% vs 1.12% ± 0.98%, P < 0.001). Expression of CD38, CD25, and TIGIT was higher, whereas that of CCR7, CD127 was lower in the Tph like cells from the IgG4-RD patients than in those from the HCs. The IgG4-RD patients with affected internal organs had higher circulating Tph like cell levels than those without (2.69% ±1.99% vs 1.23% ± 0.93%, respectively, P = 0.003). In addition, Tph like cells correlated with serum IgG and IgG4 and peripheral plasmablast levels which could be a promising biomarker for disease activity monitoring.

Phenotype, function and clinical significance of innate lymphoid cells in immunoglobulin G4-related disease.

OBJECTIVES: The innate immune system participates in immunoglobulin G4-related disease (IgG4-RD). While the role of innate lymphoid cells (ILCs) in IgG4-RD remains to be elucidated, we aimed to evaluate the phenotype, function and clinical significance of ILCs in IgG4-RD patients. METHODS: Sixty-seven untreated IgG4-RD patients and 44 age- and sex-matched healthy controls (HCs) were enrolled. Circulating and tissue infiltration of ILCs were detected by flow cytometry. Serum suppression of tumorigenicity 2 (sST2) was detected by ELISA and membrane-bound ST2 (ST2L) was detected by flow cytometry. Tissue infiltration of IL-33 was measured by immunohistochemistry staining. Real-time quantitative PCR was performed to analyse the expression pattern of ILC2-associated genes between HCs and IgG4-RD patients. In addition, correlation analysis was performed in order to evaluate the clinical significance of ILCs in IgG4-RD. RESULTS: The frequency of circulating pan ILCs in IgG4-RD patients was lower than in HCs. ILC2s were higher in IgG4-RD compared with HCs, whereas ILC1s were lower in IgG4-RD. sST2 and ST2L were higher in IgG4-RD than in HCs. Infiltration of ILC1s in the submandibular glands of IgG4-RD patients was more prominent than ILC2s. Intracellular secretion of IL-9 was increased in ILC2s of IgG4-RD patients than in HCs. Circulating ILC2s correlated positively with Treg cells and the surface expression of CD154, PD-1 and CXCR5 in ILC2s correlated positively with CD19+ B cells, serum IgG4 levels and serum IgE, respectively. CONCLUSION: ILCs and their subsets were significantly altered in IgG4-RD. We demonstrated the dysfunction of ILC2s in IgG4-RD by phenotype, correlation analysis and function investigation, revealing ILC2s participated in the pathogenesis of IgG4-RD.

Ophthalmic involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 573 patients.

PURPOSE: To investigate the clinical manifestations of orbital involvement in a large cohort of Chinese patients with IgG4-related disease (IgG4-RD). METHODS: A total of 573 patients with IgG4-related disease were included. We described and compared the demographic, clinical, laboratory and histopathologic findings from 314 patients with IgG4-related ophthalmic disease (IgG4-ROD) and 259 with extra-ophthalmic IgG4-RD. RESULTS: Male predominance was found significant in extra-ophthalmic IgG4-RD only. Patients with IgG4-ROD showed younger age at diagnosis and longer duration from onset till diagnosis. In patients with extra-ophthalmic IgG4-RD, the most commonly involved extra-ophthalmic organ was pancreas; while in IgG4-ROD patients, salivary gland was most frequently affected. Multivariate analysis exhibited IgG4-ROD was associated with allergy history, higher serum IgG4/IgG ratio, multiple organs involvement and sialoadenitis. Orbital images were reviewed in 173 (55.1%) IgG4-ROD patients. Fifty-one (29.5%) patients had multiple lesions. Lacrimal gland involvement was detected in 151 (87.3%) patients, followed by extraocular muscles (40, 23.1%), other orbital soft tissue (40, 23.1%) and trigeminal nerve (8, 4.6%). Biopsy was performed from various organs in 390 cases. A dense lymphoplasmacytic infiltration and fibrosis were the main feature in orbital specimens. Storiform fibrosis and obliterative phlebitis were absent in lacrimal gland. CONCLUSIONS: Lacrimal gland involvement was the most common orbital manifestation of IgG4-ROD. Patients with IgG4-ROD showed different characteristic in demographic, clinical, laboratory findings compared to patients with extra-ophthalmic IgG4-RD. These features might indicate potential differences in the pathogenesis of these two subgroups of IgG4-RD.

Peripheral B-Cell Immunophenotyping Identifies Heterogeneity in IgG4-Related Disease.

Objectives: To elucidate heterogeneity of IgG4-related disease (IgG4-RD) based on B cell immunophenotyping. Methods: Immunophenotyping of 4 B-cell subsets in peripheral blood from patients with active IgG4-RD (aIgG4-RD, n=105) was performed using flow cytometry to get preliminary B-cell heterogeneity spectrum. Then 10 B-cell subsets were characterized in aIgG4-RD (n = 49), remissive IgG4-RD (rIgG4-RD, n = 49), and healthy controls (HCs, n = 47), followed by principal components analysis (PCA) and cluster analysis to distinguish B-cell immunophenotypes and classify IgG4-RD patients into subgroups. Results: Cluster analysis identified two endotypes in 105 aIgG4-RD patients based on 4 B-cell subsets: Group1 with higher Breg and naive B cells (n = 48), and Group2 with higher plasmablasts and memory B cells (MBCs) (n = 57). PCA indicated that aIgG4-RD consisted of plasmablast-naive B cell and MBCs-Breg axes abnormalities. There was a negative relationship between naive B cells and disease activity. Both plasmablasts and MBCs were positively associated with serological biomarkers. Cluster analysis stratified aIgG4-RD patients into 3 subgroups based on 10 B-cell subsets: subgroup1 with low MBCs and normal Breg, subgroup2 with high MBCs and low Breg, and subgroup3 with high plasmablasts and low naive B cells. Patients in subroup2 and subgroup3 were more likely to be resistant to treatment. Conclusion: Patients with aIgG4-RD can be divided into 3 subgroups based on B cell heterogeneity. The B cell immunophenotyping could help elucidate the pathogenesis of IgG4-RD, identify patients with potential refractory IgG4-RD, and provide important information for the development of new therapies.

Tuberculosis infection screening in children with close contact: a hospital-based study.

BACKGROUND: Identifying and prioritizing at-risk populations is critical for pediatric tuberculosis control. We aimed to identify a latent tuberculosis infection (LTBI) screening strategy that is appropriate for the Chinese context among children with different TB exposure levels and to explore its clinical importance. METHODS: During 2013-2015, we enrolled hospitalized children with suspected respiratory infectious disease (RID) for LTBI screening using the tuberculin skin test (TST) and interferon-γ release assay (IGRA) T-SPOT.TB as part of a work up for their RID. Participants with confirmed diagnosis were classified into three subgroups according to level of exposure to TB: no reported contact risk, with household contact risk, and with non-household contact risk. RESULTS: A total 6202 children (median age: 4.76 years; interquartile range: 1.0-8.0 years) were enrolled. Children with no reported contact risk had the lowest proportions of positive results for the IGRA (0.7%) and TST (3.3%). The proportion of positive results for each test was higher for household contacts than non-household contacts. The TST positive proportion was much higher than that for the IGRA in all three groups. Children with IGRA+/TST+ results had larger indurations than those with IGRA- /TST+ results (15 mm vs. 13 mm, P = 0.02). For IGRA, older age (> 5 years) and non-household or household contact risk were associated with a positive result. CONCLUSIONS: Positive IGRA results in children with a contact risk can serve as a critical reference for LTBI management. IGRA can be used, in preference to TST, for Chinese children with a TB exposure risk.

Transcriptome analysis reveals possible antitumor mechanism of Chlorella exopolysaccharide.

Microalgae, one of the most important classes of biomass producers, can produce exopolysaccharides similar to bacteria. The exopolysaccharide from Chlorella (CEPS) displays remarkable anticancer activity the mechanism of which remains to be elucidated. In this study, we analyzed the inhibitory effect of CEPS on the growth of HeLa cells. The results showed that CEPS inhibited the proliferation, decreased the viability, and changed the morphology of HeLa cells. Transcriptome analysis showed that 1894 genes were differentially expressed in the CEPS-treated group compared with the control group, including 1076 genes that were upregulated and 818 genes that were downregulated. The results of gene function enrichment analysis showed that the differentially expressed genes (DEGs) were significantly enriched in apoptosis and tumor-related biological processes and participated in several cancer and apoptosisrelated signaling pathways, including the MAPK signaling pathway, TNF signaling pathway, and the PI3K-Akt signaling pathway. The protein-protein interaction network identified 13 DEGs including PTPN11, RSAD2, ISG15, IFIT1, MX2, IFIT2, OASL, OAS1, JUN, OAS2, XAF1, ISG20, and IRF9 as hub genes. Our results suggest that CEPS is a promising therapeutic drug for the follow-up interventional therapy of cancer.

Differences in clinical characteristics of IgG4-related disease across age groups: a prospective study of 737 patients.

OBJECTIVE: The aim of this study was to compare the clinical characteristics of IgG4-related disease (IgG4-RD) among different age groups. METHODS: We conducted a prospective study of 737 patients who were newly diagnosed with IgG4-RD and compared detailed demographic features, organ involvements, laboratory tests, treatments and outcomes across age groups. The patients were divided into five groups according to their age at diagnosis: ≤39, 40-49, 50-59, 60-69 and ≥70 years. The clinical characteristics of paediatric patients were also described. RESULTS: Sex ratio, disease duration, allergy history and clinical symptoms were significantly different across age groups. Besides, the proportions of superficial organ involvement (lacrimal gland and sinus) decreased with age, while the proportions of internal organ involvement (pancreas, biliary tract, retroperitoneal tissue, lung and prostate) increased with age, which was more prominent in male patients. Mikulicz's disease was the most common manifestation (70%) in paediatric IgG4-RD patients. Multiple Cox analysis identified that age ≤56 years at diagnosis was an independent risk factor of relapse. CONCLUSION: We revealed the impact of age on clinical characteristics of IgG4-RD, which indicated that different management might be required among different age groups.

Evidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials.

BACKGROUND: Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention. METHODS: Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised. RESULTS: A total of 44 676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B). INTERPRETATION: Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.

ZKSCAN3 drives tumor metastasis via integrin ß4/FAK/AKT mediated epithelial-mesenchymal transition in hepatocellular carcinoma.

BACKGROUND: ZKSCAN3, a zinc-finger transcription factor containing KRAB and SCAN domains, has been reported to be regulated in several human cancers. However, its expression and function in hepatocellular carcinoma (HCC) remains unknown. METHODS: Expression of ZKSCAN3 in HCC was analyzed by western blotting, immunohistochemistry, and real time PCR. Its correlation with the clinicopathological characteristics and prognosis of HCC patients was analyzed. The effects of ZKSCAN3 on the migration and invasion were determined by Transwell assays. The potential downstream targets of ZKSCAN3 and related molecular mechanisms were clarified by Western blot and dual luciferase reporter assay. RESULTS: In this study, we demonstrated for the first time that ZKSCAN3 mRNA and protein was up-regulated in HCC tissues and cell lines. High ZKSCAN3 expression was significantly associated with poor prognostic features, including advanced TNM stage and vascular invasion. For 5-year survival, ZKSCAN3 served as a potential prognostic marker of HCC patients. Functionally, ZKSCAN3 promoted migration, invasion and EMT progress via directly binding to integrin ß4 (ITGB4) promoter and enhanced its expression. Further investigation proved that ITGB4 triggers the focal adhesion kinase (FAK) to activate the AKT signaling pathway. Inactivation of FAK and AKT by their specific inhibitors respectively reversed the effects of ZKSCAN3 on HCC cells. In addition, we demonstrated that ZKSCAN3 expression was regulated by miR-124. In HCC tissues. MiR-124 has an inverse correlation with ZKSCAN3 expression. CONCLUSION: We demonstrate for the first time that ZKSCAN3 is overexpressed in HCC tissues and promotes migration, invasion and EMT process through ITGB4-dependent FAK/AKT activation, which was regulated by miR-124, suggesting the potential therapeutic value for HCC.

Longitudinal trajectories of Alzheimer's ATN biomarkers in elderly persons without dementia.

BACKGROUND: Models of Alzheimer's disease (AD) pathophysiology posit that amyloidosis [A] precedes and accelerates tau pathology [T] that leads to neurodegeneration [N]. Besides this A-T-N sequence, other biomarker sequences are possible. This current work investigates and compares the longitudinal trajectories of Alzheimer's ATN biomarker profiles in non-demented elderly adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. METHODS: Based on the ATN classification system, 262 individuals were identified before dementia diagnosis and accompanied by baseline and follow-up data of ATN biomarkers (CSF Aß42, p-tau, and FDG-PET). We recorded the conversion processes in ATN biomarkers during follow-up, then analyzed the possible longitudinal trajectories and estimated the conversion rate and temporal evolution of biomarker changes. To evaluate how biomarkers changed over time, we used linear mixed-effects models. RESULTS: During a 6-120-month follow-up period, there were four patterns of longitudinal changes in Alzheimer's ATN biomarker profiles, from all negative to positive through the course of the disease. The most common pattern is that A pathology biomarker first emerges. As well as the classical A-T-N sequence, other "A-first," "T-first," and "N-first" biomarker pathways were found. The N-A-T sequence had the fastest rate of pathological progression (mean 65.00 months), followed by A-T-N (mean 67.07 months), T-A-N (mean 68.85 months), and A-N-T sequences (mean 98.14 months). CONCLUSIONS: Our current work presents a comprehensive analysis of longitudinal trajectories of Alzheimer's ATN biomarkers in non-demented elderly adults. Stratifying disease into subtypes depending on the temporal evolution of biomarkers will benefit the early recognition and treatment.

Long noncoding RNA LINC00173 is downregulated in cervical cancer and inhibits cell proliferation and invasion by modulating the miR-182-5p/FBXW7 axis.

Accumulating evidence has supported the concept that long noncoding RNAs (lncRNAs) participate in the initiation and progression of human cervical cancer (CC). The long intergenic nonprotein-coding RNA 173 (LINC00173) is a recently identified cancer-associated factor. However, the expression and biological role of LINC00173 in CC are poorly understood. Here, for the first time, we found that the expression of LINC00173 was decreased in CC tissues compared with that in nontumor tissues. Data from The Cancer Genome Atlas (TCGA) further revealed that the downregulated expression of LINC00173 in CC tissues was correlated with poor survival. Functionally, LINC00173 overexpression suppressed HeLa cell proliferation via induction of G0/G1 phase arrest. Ectopic expression of LINC00173 also repressed the invasiveness of HeLa cells. Conversely, LINC00173 depletion resulted in the enhanced proliferation and invasiveness of C33A cells. Mechanistically, LINC00173 functioned as a molecular sponge for miR-182-5p and inversely regulated the miR-182-5p level in CC cells. F-box and WD repeat domain-containing 7 (FBXW7) was identified as the target of miR-182-5p. LINC00173 overexpression enhanced the FBXW7 level via regulation of miR-182-5p in HeLa Cells. More importantly, the inhibitory effects of LINC00173 on HeLa cell proliferation and invasiveness were reversed by FBXW7 silencing. Taken together, the results indicate that the LINC00173/miR-182-5p/FBXW7 axis is critical for CC progression, which might offer new insights into effective therapy for CC.