Intrauterine infusion of platelet-rich plasma improves fibrosis by transforming growth factor beta 1/Smad pathway in a rat intrauterine adhesion model.

This study aims to elucidate the effects of Platelet-rich plasma (PRP) in fibrosis development in intrauterine adhesion (IUA), and the associated underlying mechanisms are also explored, which are expected to be a potential therapeutic scheme for IUA. In this research, PRP was obtained and prepared from the peripheral venous blood of rats. A rat model was induced by mechanical injury. Further, PRP was directly injected into the uterus for treatment. The appearance and shape of the uterus were assessed based on the tissues harvested. The fibrosis biomarker levels were analyzed. The transforming growth factor beta 1 (TGF-ß1) and Mothers against decapentaplegic homolog 7 (Smad7) levels, the phosphorylation of Smad2 (p-Smad2), and the phosphorylation of Smad3 (p-Smad3) were analyzed, and the molecular mechanism was investigated by rescue experiments. It was found that PRP improved the appearance and shape of the uterus in IUA and increased endometrial thickness and gland numbers. The administration of PRP resulted in a decrease in the expressions of fibrosis markers including collagen I, α-SMA, and fibronectin. Furthermore, PRP increased Smad7 levels and decreased TGF-ß1 levels, p-Smad2, and p-Smad3. Meanwhile, administration of TGF-ß1 activator reversed the therapeutic effects of PRP in IUA. Collectively, the intrauterine infusion of PRP can promote endometrial damage recovery and improve endometrial fibrosis via the TGF-ß1/Smad pathway. Hence, PRP can be a potential therapeutic strategy for IUA.

Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD).

Nonalcoholic fatty liver disease (NAFLD) has become an increasingly common disease in Western countries and has become the major cause of liver cirrhosis or hepatocellular carcinoma (HCC) in addition to viral hepatitis in recent decades. Furthermore, studies have shown that NAFLD is inextricably linked to the development of extrahepatic diseases. However, there is currently no effective treatment to cure NAFLD. In addition, in 2020, NAFLD was renamed metabolic dysfunction fatty liver disease (MAFLD) to show that its pathogenesis is closely related to metabolic disorders. Recent studies have reported that the development of MAFLD is inextricably associated with mitochondrial dysfunction in hepatocytes and hepatic stellate cells (HSCs). Simultaneously, mitochondrial stress caused by structural and functional disorders stimulates the occurrence and accumulation of fat and lipo-toxicity in hepatocytes and HSCs. In addition, the interaction between mitochondrial dysfunction and the liver-gut axis has also become a new point during the development of MAFLD. In this review, we summarize the effects of several potential treatment strategies for MAFLD, including antioxidants, reagents, and intestinal microorganisms and metabolites.

Corrigendum: Study on the pathogenesis of MiR-6324 regulating diarrheal irritable bowel syndrome and bioinformatics analysis.

[This corrects the article DOI: 10.3389/fphar.2023.1044330.].

Psychometric testing of the Chinese National Health Service Sustainability Model as an instrument to assess innovation in Chinese nursing settings.

OBJECTIVES: To conduct psychometric testing of the Chinese version of the National Health Service Sustainability Model as an instrument to assess the sustainability of innovation in the Chinese nursing setting. BACKGROUND: Evidence-based practice is recognized worldwide as a way to improve the quality of healthcare; however, many evidence-based practice programmes decline over time and do not sustain the benefits of their improvements. A sustainability assessment tool is used internationally but its use has not been validated in China. DESIGN: A methodological study to test instrument validity and reliability. METHODS: The data collection was conducted from 15 June 2022 to 31 August 2022. The internal consistency of the Chinese version of the sustainability model was measured with Cronbach's alpha. Confirmatory factor analysis was used to test the model's structural validity. RESULTS: Four hundred eighty-three questionnaires were returned, of which 478 were valid. The short time taken to evaluate the Chinese version of the sustainability model demonstrated its efficiency and ability to adapt to a busy clinical environment. The confirmatory factor analysis showed a good fit model and supported the convergence validity of the sustainability model. The Cronbach's alpha coefficient was 0.905 for the total scale, which indicated good internal consistency. CONCLUSIONS: The results of this study suggest that the Chinese version of the sustainability model is a valid, reliable and efficient tool for measuring the sustainability of evidence-based practices in Chinese nursing settings.

Angiogenesis-An Emerging Role in Organ Fibrosis.

In recent years, the study of lymphangiogenesis and fibrotic diseases has made considerable achievements, and accumulating evidence indicates that lymphangiogenesis plays a key role in the process of fibrosis in various organs. Although the effects of lymphangiogenesis on fibrosis disease have not been conclusively determined due to different disease models and pathological stages of organ fibrosis, its importance in the development of fibrosis is unquestionable. Therefore, we expounded on the characteristics of lymphangiogenesis in fibrotic diseases from the effects of lymphangiogenesis on fibrosis, the source of lymphatic endothelial cells (LECs), the mechanism of fibrosis-related lymphangiogenesis, and the therapeutic effect of intervening lymphangiogenesis on fibrosis. We found that expansion of LECs or lymphatic networks occurs through original endothelial cell budding or macrophage differentiation into LECs, and the vascular endothelial growth factor C (VEGFC)/vascular endothelial growth factor receptor (VEGFR3) pathway is central in fibrosis-related lymphangiogenesis. Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), as a receptor of LECs, is also involved in the regulation of lymphangiogenesis. Intervention with lymphangiogenesis improves fibrosis to some extent. In the complex organ fibrosis microenvironment, a variety of functional cells, inflammatory factors and chemokines synergistically or antagonistically form the complex network involved in fibrosis-related lymphangiogenesis and regulate the progression of fibrosis disease. Further clarifying the formation of a new fibrosis-related lymphangiogenesis network may potentially provide new strategies for the treatment of fibrosis disease.

Construction of an Emotional Lexicon of Patients With Breast Cancer: Development and Sentiment Analysis.

BACKGROUND: The innovative method of sentiment analysis based on an emotional lexicon shows prominent advantages in capturing emotional information, such as individual attitudes, experiences, and needs, which provides a new perspective and method for emotion recognition and management for patients with breast cancer (BC). However, at present, sentiment analysis in the field of BC is limited, and there is no emotional lexicon for this field. Therefore, it is necessary to construct an emotional lexicon that conforms to the characteristics of patients with BC so as to provide a new tool for accurate identification and analysis of the patients' emotions and a new method for their personalized emotion management. OBJECTIVE: This study aimed to construct an emotional lexicon of patients with BC. METHODS: Emotional words were obtained by merging the words in 2 general sentiment lexicons, the Chinese Linguistic Inquiry and Word Count (C-LIWC) and HowNet, and the words in text corpora acquired from patients with BC via Weibo, semistructured interviews, and expressive writing. The lexicon was constructed using manual annotation and classification under the guidance of Russell's valence-arousal space. Ekman's basic emotional categories, Lazarus' cognitive appraisal theory of emotion, and a qualitative text analysis based on the text corpora of patients with BC were combined to determine the fine-grained emotional categories of the lexicon we constructed. Precision, recall, and the F1-score were used to evaluate the lexicon's performance. RESULTS: The text corpora collected from patients in different stages of BC included 150 written materials, 17 interviews, and 6689 original posts and comments from Weibo, with a total of 1,923,593 Chinese characters. The emotional lexicon of patients with BC contained 9357 words and covered 8 fine-grained emotional categories: joy, anger, sadness, fear, disgust, surprise, somatic symptoms, and BC terminology. Experimental results showed that precision, recall, and the F1-score of positive emotional words were 98.42%, 99.73%, and 99.07%, respectively, and those of negative emotional words were 99.73%, 98.38%, and 99.05%, respectively, which all significantly outperformed the C-LIWC and HowNet. CONCLUSIONS: The emotional lexicon with fine-grained emotional categories conforms to the characteristics of patients with BC. Its performance related to identifying and classifying domain-specific emotional words in BC is better compared to the C-LIWC and HowNet. This lexicon not only provides a new tool for sentiment analysis in the field of BC but also provides a new perspective for recognizing the specific emotional state and needs of patients with BC and formulating tailored emotional management plans.

GLP-1 receptor agonist, liraglutide, protects podocytes from apoptosis in diabetic nephropathy by promoting white fat browning.

Glucagon like peptide-1 receptor agonists (GLP-1RAs) belong to the class of incretin drugs. Incretin is a hormone secreted into blood by intestinal cells after food stimulation that induces insulin secretion. Liraglutide is a long-acting GLP-1RA that can reduce blood pressure, blood lipids, and inflammation. Previous studies showed that liraglutide can promote white fat browning and improve renal outcomes in patients with type 2 diabetes mellitus. However, no studies have linked white fat browning to kidney damage. The objective of this study was to investigate the effects of liraglutide-induced white fat browning on podocyte apoptosis in diabetic nephropathy. We also aimed to determine whether podocytes express glucagon like peptide-1 receptor (GLP-1R) and if liraglutide directly affects podocytes via GLP-1R. We assessed fat and renal function in db/db and wild-type mice and the effects of adipocyte conditioned medium on cultured podocytes. Liraglutide (400 mg/kg/d) was subcutaneously injected for 8 weeks. Liraglutide promoted white fat browning in vivo. During adipogenic differentiation of 3T3-L1 cells in vitro, liraglutide also upregulated expression of peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC1α) and uncoupling protein 1 (UCP1), which can induce white fat browning in vitro. Furthermore, we found that supernatant from 3T3-L1 cells stimulated by liraglutide reduced podocyte apoptosis. The inhibitory effect of liraglutide on apoptosis was eliminated by exogenous TNF-α. Finally, podocytes express GLP-1R. In vivo and in vitro studies showed that the apoptosis of podocytes in diabetic nephropathy may be related to the effect of liraglutide on promoting white lipid browning. Similarly, liraglutide may directly affect podocytes via GLP-1R.

Presence of Rare Variants is Associated with Poorer Survival in Chinese Patients with Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with phenotypic and genetic heterogeneity. Recent studies have suggested an oligogenic basis of ALS, in which the co-occurrence of two or more genetic variants has additive or synergistic deleterious effects. To assess the contribution of possible oligogenic inheritance, we profiled a panel of 43 relevant genes in 57 sporadic ALS (sALS) patients and eight familial ALS (fALS) patients from five pedigrees in east China. We filtered rare variants using the combination of the Exome Aggregation Consortium, the 1000 Genomes and the HuaBiao Project. We analyzed patients with multiple rare variants in 43 known ALS causative genes and the genotype-phenotype correlation. Overall, we detected 30 rare variants in 16 different genes and found that 16 of the sALS patients and all the fALS patients examined harbored at least one variant in the investigated genes, among which two sALS and four fALS patients harbored two or more variants. Of note, the sALS patients with one or more variants in ALS genes had worse survival than the patients with no variants. Typically, in one fALS pedigree with three variants, the family member with three variants (Superoxide dismutase 1 (SOD1) p.V48A,  Optineurin (OPTN) p.A433V and TANK binding kinase 1 (TBK1) p.R573H) exhibited much more severe disease phenotype than the member carrying one variant (TBK1 p.R573H). Our findings suggest that rare variants could exert a negative prognostic effect, thereby supporting the oligogenic inheritance of ALS.

Investigation of Surface Layers on Biological and Synthetic Hydroxyapatites Based on Bone Mineralization Process.

In this review, the current status of the influence of added ions (i.e., SiO44-, CO32-, etc.) and surface states (i.e., hydrated and non-apatite layers) on the biocompatibility nature of hydroxyapatite (HA, Ca10(PO4)6(OH)2) is discussed. It is well known that HA is a type of calcium phosphate with high biocompatibility that is present in biological hard tissues such as bones and enamel. This biomedical material has been extensively studied due to its osteogenic properties. The chemical composition and crystalline structure of HA change depending on the synthetic method and the addition of other ions, thereby affecting the surface properties related to biocompatibility. This review illustrates the structural and surface properties of HA substituted with ions such as silicate, carbonate, and other elemental ions. The importance of the surface characteristics of HA and its components, the hydration layers, and the non-apatite layers for the effective control of biomedical function, as well as their relationship at the interface to improve biocompatibility, has been highlighted. Since the interfacial properties will affect protein adsorption and cell adhesion, the analysis of their properties may provide ideas for effective bone formation and regeneration mechanisms.

Study on the pathogenesis of MiR-6324 regulating diarrheal irritable bowel syndrome and bioinformatics analysis.

Objective: To investigate the pathogenesis of IBS-D by bioinformatics analysis of the differential microRNAs in rat colon tissue and to analyze and predict the function of their target genes. Methods: Twenty male Wistar rats of SPF class were randomly divided into two groups, the model group was manipulated using the colorectal dilatation method + chronic restraint stress method to establish the IBS-D model; while the blank group stroked the perineum at the same frequency. Screening of differential miRNAs after High-throughput sequencing of rat colon tissue. GO and KEGG analysis of target genes using the DAVID website, further mapping using RStudio software; the STRING database and the Cytoscape software were used to obtain the protein interaction network (PPI) of the target genes as well as the core genes. Finally, qPCR was used to detect the expression of target genes in the colon tissue of two groups of rats. Results: After the screening, miR-6324 was obtained as the key of this study. The GO analysis of target genes of miR-6324 is mainly involved in protein phosphorylation, positive regulation of cell proliferation, and intracellular signal transduction; it affects a variety of cellular components such as cytoplasm, nucleus, and organelles on the intracellular surface; it is also involved in molecular functions such as protein binding, ATP binding, and DNA binding. KEGG analysis showed that the intersecting target genes were mainly enriched in cancer pathways, proteoglycans in cancer, neurotrophic signaling pathway, etc. The protein-protein interaction network screened out the core genes mainly Ube2k, Rnf41, Cblb, Nek2, Nde1, Cep131, Tgfb2, Qsox1, and Tmsb4x. The qPCR results showed that the expression of miR-6324 decreased in the model group, but the decrease was not significant. Conclusion: miR-6324 may be involved in the pathogenesis of IBS-D as a potential biological target and provide further ideas for research on the pathogenesis of the disease or treatment options.

Analytical investigation of nano-bio interfacial protein mediation for fibroblast adhesion on hydroxyapatite nanoparticles.

A quartz crystal microbalance with dissipation (QCM-D) analysis was used to investigate fetal bovine serum (FBS) protein preadsorption on a hydroxyapatite (HAp) surface and the subsequent adhesion process of fibroblasts as compared with the case of oxidized poly(styrene) (PSox). The results showed that the preadsorption of FBS proteins on HAp promoted the subsequent initial cell adhesion ability. Moreover, the measured frequency (Δf) and dissipation shift (ΔD) curves, ΔD-Δf plots and viscoelastic analysis were used to study the initial cell adhesion process in real time. It was suggested that FBS-HAp showed sensitive changes in mass and viscoelasticity as compared with FBS-PSox, which realized the in situ reflection of the cell adhesion state, and the interfacial reactions between the cells and FBS-HAp surfaces such as dehydration and binding occurred to promote the initial cell adhesion and spreading. The viscoelastic analysis of the interface layer showed that the adhered cells on FBS-HAp could secrete some viscous substances such as extracellular matrix (ECM) proteins at the interfaces to provide good adhesion behaviors, and the Voigt-based viscoelastic model could clearly reveal the cellular interfacial viscoelasticity depending on the substrate surface. In addition, the morphology of cells was observed by confocal laser scanning microscopy (CLSM) and atomic force microscopy (AFM), and it was found that the pseudopodia were more uniformly stretched on FBS-HAp than on FBS-PSox. Furthermore, the state of the interfacial protein layer was analyzed by localized Fourier-transform infrared (FT-IR) spectroscopy and fluorescence microscopy (FLM), and it was indicated that the type of substrate affects the formation state of ECM proteins, resulting in changes in cell adhesion properties and morphology. The abundant formation of connective proteins (i.e., collagen type I) on FBS-HAp promoted subsequent pseudopodia formation and cell spreading. Therefore, the initial adhesion properties of fibroblasts on the FBS-HAp surface were systematically studied, which is of great importance for understanding the interfacial interaction between biomaterials and cells, and has great application value in biomedical fields.

Terahertz wave modulation properties of graphene with different excitation laser power.

The terahertz wave modulation properties of graphene were investigated using an external 975 nm continuous wave laser with different power. Upon excitation laser, the transmission and modulation depth was measured using terahertz time-domain spectroscopy. The experimental results showed that the modulation depth of monolayer graphene and 3-layer graphene was 16% and 32% under the 1495 mW excitation power. Further, we analyzed the graphene modulation mechanism based on the Drude model and the thin-film approximation. Both theoretical analysis and calculation results showed that the terahertz wave could be modulated using graphene with different excitation laser power.

Investigation into self-assembled collagen arrays guided by the surface properties of polyimide films.

The mechanism of highly-oriented collagen (Col) fibril arrays on rubbed polyimide (PI) films was investigated in order to understand the interfacial Col-PI interactions. It was found that the orientation of the surface functional groups of the rubbed PI films was most effectively controlled and optimized by the rubbing conditions. In particular, nano-grooves with a width of 100-600 nm and a depth of 2-10 nm were formed on the rubbed PI films at a rubbing strength of 2.4 m, leading to the formation of the highest density of the Col fibril array. Moreover, highly-oriented Col fibrils were formed inside the nano-grooves by the formation of hydrogen bonds between the CO of the imide groups (@ rubbed PI films) and the N-H of the amino groups (@ ß-Sheets of Col molecules), resulting in the orientation of the Col molecules and subsequent assembly to the fibrils. Thus, the orientation and density of the fibril arrays on the rubbed PI films were successfully controlled by the interfacial interactions between the ß-Sheet component of Col and the nano-groove surfaces of the rubbed PI films. Therefore, the novel technology of this study will provide an effective method to fabricate the one-directional fibrous nanostructures and to understand how to control the orientation of biomolecules in vitro.

Effect of Multimedia Health Education on Psychological Burden, Quality of Life Ability, and Self-Efficacy of Congenital Microtia.

Aims: To investigate the effects of multimedia health education on psychological burden, quality of life, and self-efficacy of patients with congenital microtia. Materials and Methods: Eighty cases of patients with congenital microtia treated and cared for in our hospital from June 2018 to June 2022 were selected according to the numerical table method as retrospective study subjects and divided into 40 cases each in the comparison group and the observation group. The comparison group implemented conventional health education and discharge instruction, and the observation group implemented multimedia health education care to compare the effects of self-efficacy, self-care ability and psychological burden of patients in the two groups. Results: Before care, the two groups had no statistically significant difference in the quality of life scores (P > 0.05). Aftercare, the mental vitality scores, social interaction scores, emotional limitation scores, and mental status of patients in the observation group were significantly higher than those in the comparison group (P < 0.05). Before nursing care, there was no statistically significant difference in the nursing ability and anxiety-depression scores between the two groups (P > 0.05). After nursing care, the health knowledge level, self-care skills, self-care responsibility, and self-concept of the observation group were higher than the comparison group, while the depression-emotional disorder scores were significantly lower than the comparison group (P < 0.05). Conclusion: Routine health education and discharge instruction combined with multimedia health education care can effectively improve the quality of life of patients with congenital microtia, reduce adverse emotions, and improve patients' sense of self-efficacy.

Oxidative stress-mediated mitochondrial fission promotes hepatic stellate cell activation via stimulating oxidative phosphorylation.

Previous studies have demonstrated dysregulated mitochondrial dynamics in fibrotic livers and hepatocytes. Little is currently known about how mitochondrial dynamics are involved, nor is it clear how mitochondrial dynamics participate in hepatic stellate cell (HSC) activation. In the present study, we investigated the role of mitochondrial dynamics in HSC activation and the underlying mechanisms. We verified that mitochondrial fission was enhanced in human and mouse fibrotic livers and active HSCs. Moreover, increased mitochondrial fission driven by fis1 overexpression could promote HSC activation. Inhibiting mitochondrial fission using mitochondrial fission inhibitor-1 (Mdivi-1) could inhibit activation and induce apoptosis of active HSCs, indicating that increased mitochondrial fission is essential for HSC activation. Mdivi-1 treatment also induced apoptosis in active HSCs in vivo and thus ameliorated CCl4-induced liver fibrosis. We also found that oxidative phosphorylation (OxPhos) was increased in active HSCs, and OxPhos inhibitors inhibited activation and induced apoptosis in active HSCs. Moreover, increasing mitochondrial fission upregulated OxPhos, while inhibiting mitochondrial fission downregulated OxPhos, suggesting that mitochondrial fission stimulates OxPhos during HSC activation. Next, we found that inhibition of oxidative stress using mitoquinone mesylate (mitoQ) and Tempol inhibited mitochondrial fission and OxPhos and induced apoptosis in active HSCs, suggesting that oxidative stress contributes to excessive mitochondrial fission during HSC activation. In conclusion, our study revealed that oxidative stress contributes to enhanced mitochondrial fission, which triggers OxPhos during HSC activation. Importantly, inhibiting mitochondrial fission has huge prospects for alleviating liver fibrosis by eliminating active HSCs.

Rubbing-Assisted Approach for Fabricating Oriented Nanobiomaterials.

The highly-oriented structures in biological tissues play an important role in determining the functions of the tissues. In order to artificially fabricate oriented nanostructures similar to biological tissues, it is necessary to understand the oriented mechanism and invent the techniques for controlling the oriented structure of nanobiomaterials. In this review, the oriented structures in biological tissues were reviewed and the techniques for producing highly-oriented nanobiomaterials by imitating the oriented organic/inorganic nanocomposite mechanism of the biological tissues were summarized. In particular, we introduce a fabrication technology for the highly-oriented structure of nanobiomaterials on the surface of a rubbed polyimide film that has physicochemical anisotropy in order to further form the highly-oriented organic/inorganic nanocomposite structures based on interface interaction. This is an effective technology to fabricate one-directional nanobiomaterials by a biomimetic process, indicating the potential for wide application in the biomedical field.

Biomimetic Mineralization in External Layer of Decalcified Fish Scale.

The mineralization process of the osseous layer, which is highly calcified in vivo, was successfully imitated by the immersion process of the decalcified fish scales in simplified simulated body fluid (SSBF). An alkali treatment was used to modify the native collagen in the decalcified Tilapia fish scale. After the alkali treatment, the mineralization was facilitated in SSBF. The XRD patterns and SEM-EDS observation results demonstrated that the externally-mineralized layers by the immersion process were highly similar to the osseous layer containing lower-crystalline hydroxyapatite, suggesting that the simple biomimetic precipitation process was developed.

Perceptions of nurses and physicians on pay-for-performance in hospital: A systematic review of qualitative studies.

AIMS: This study aimed to systematically examine perceptions of nurses and physicians on pay-for-performance in hospital. BACKGROUND: Pay-for-performance projects have proliferated over the past two decades, most systematic reviews of which solely focused on its effectiveness in primary health care and the physicians' or nurses' attitudes. However, systematic reviews of qualitative approaches for better examining perceptions of both nurses and physicians in hospital were lacking. EVALUATION: Electronic databases were systematically searched with date from the inception to 31 December 2020. Meta-aggregation synthesis methodology and the conceptual framework of the theory of planned behaviour were used to summarize findings. KEY ISSUES: A total of nine studies were included. Three major synthesized themes were identified: (1) perceptions of the motivation effects and positive outcomes, (2) perceptions about the design defects and negative effects and (3) perceptions of the obstacles in the implementation process. CONCLUSION: To maximize the intended positive effects, nurses' and physicians' perceptions should be considered and incorporated into the project design and implementation stage. IMPLICATIONS FOR NURSING MANAGEMENT: The paper gives enlightenment to nurse managers on improving and advancing the cause of nurses when planning for or evaluating their institutions' policies on pay-for-performance in the future research.

Exogenous Wnt1 Prevents Acute Kidney Injury and Its Subsequent Progression to Chronic Kidney Disease.

Studies suggest that Wnt/ß-catenin agonists are beneficial in the treatment of acute kidney injury (AKI); however, it remains elusive about its role in the prevention of AKI and its progression to chronic kidney disease (CKD). In this study, renal Wnt/ß-catenin signaling was either activated by overexpression of exogenous Wnt1 or inhibited by administration with ICG-001, a small molecule inhibitor of ß-catenin signaling, before mice were subjected to ischemia/reperfusion injury (IRI) to induce AKI and subsequent CKD. Our results showed that in vivo expression of exogenous Wnt1 before IR protected mice against AKI, and impeded the progression of AKI to CKD in mice, as evidenced by both blood biochemical and kidney histological analyses. In contrast, pre-treatment of ICG-001 before IR had no effect on renal Wnt/ß-catenin signaling or the progression of AKI to CKD. Mechanistically, in vivo expression of exogenous Wnt1 before IR suppressed the expression of proapoptotic proteins in AKI mice, and reduced inflammatory responses in both AKI and CKD mice. Additionally, exogenous Wnt1 inhibited apoptosis of tubular cells induced by hypoxia-reoxygenation (H/R) treatment in vitro. To conclude, the present study provides evidences to support the preventive effect of Wnt/ß-catenin activation on IR-related AKI and its subsequent progression to CKD.

Role of Blood Neurofilaments in the Prognosis of Amyotrophic Lateral Sclerosis: A Meta-Analysis.

Background: Neurofilaments in cerebrospinal fluid (CSF) and in blood are considered promising biomarkers of amyotrophic lateral sclerosis (ALS) because their levels can be significantly increased in patients with ALS. However, the roles of neurofilaments, especially blood neurofilaments, in the prognosis of ALS are inconsistent. We performed a meta-analysis to explore the prognostic roles of blood neurofilaments in ALS patients. Methods: We searched all relevant studies on the relationship between blood neurofilament levels and the prognosis of ALS patients in PubMed, Embase, Scopus, and Web of Science before February 2, 2021. The quality of the included articles was assessed using the Quality in Prognosis Studies (QUIPS) scale, and R (version 4.02) was used for statistical analysis. Results: Fourteen articles were selected, covering 1,619 ALS patients. The results showed that higher blood neurofilament light chain (NfL) levels in ALS patients were associated with a higher risk of death [medium vs. low NfL level: HR = 2.43, 95% CI (1.34-4.39), p < 0.01; high vs. low NfL level: HR = 4.51, 95% CI (2.45-8.32), p < 0.01]. There was a positive correlation between blood phosphorylated neurofilament heavy chain (pNfH) levels and risk of death in ALS patients [HR = 1.87, 95% CI (1.35-2.59), p < 0.01]. The levels of NfL and pNfH in blood positively correlated with disease progression rate (DPR) of ALS patients [NfL: summary r = 0.53, 95% CI (0.45-0.60), p < 0.01; pNfH: summary r = 0.51, 95% CI (0.24-0.71), p < 0.01]. Conclusion: The blood neurofilament levels can predict the prognosis of ALS patients; specifically, higher levels of blood neurofilaments are associated with a greater risk of death.