Prognostic value and molecular mechanisms of OAS1 in lung adenocarcinoma.

BACKGROUND: The expression of 2'-5'-oligoadenylate synthetase 1 (OAS1) in lung cancer has been validated in numerous studies. However, the prognostic value of OAS1 expression in lung adenocarcinoma (LUAD) still remains unclear. This study aimed to reveal the prognostic value and associated molecular mechanisms of OAS1 expression in LUAD. METHODS: Gene expression data of LUAD were extracted from online databases. Gene and protein expression levels of OAS1 in LUAD and normal samples were revealed, followed by prognostic analysis of OAS1. Next, we conducted a thorough bioinformatics analysis to examine the enrichment of key functional and biological signaling pathways and their correlation with the abundance of immune cells. The independent prognoses, drug responses, and PPI networks associated with OAS1 were analyzed. OAS1 expression was evaluated in LUAD tissues and cell lines. OAS1 was knocked down by siRNA transfection, followed by CCK8, colony formation, and wound-healing assays. RESULTS: Gene and protein expression levels of OAS1 in LUAD samples were significantly higher than those in normal samples (all P < 0.05). OAS1 stimulation were correlated with poor prognosis, lymph node metastasis, advanced tumor stage, immune cells, and immunomodulators. The prognostic value of OAS1 in LUAD was determined via univariate regression analysis. In total, 10 OAS1-associated genes were revealed via PPI analysis of OAS1, which were primarily enriched in functions, such as the negative regulation of viral genome replication. Transcriptional analysis revealed several OAS1-related interactions, including STAT3-miR-21-OAS1. STAT3 was overexpressed and miR-21 was expressed in LUAD cells. Upregulation of OAS1 protein was determined in LUAD tissues and cell lines. OAS1 knockdown significantly reduced proliferation and migration of LUAD cells. CONCLUSIONS: OAS1 overexpression influenced survival and immune cell infiltration in patients with LUAD, which might be a potential prognostic gene for LUAD. Moreover, OAS1 contributed to LUAD progression by participating in STAT3-miR-21-OAS1 axis.

Quma Tongluo Prescription in the Treatment of Chronic Oxaliplatin Related Peripheral Neuropathy: A Single-Center, Open, Randomized Controlled Study.

Objective: To observe the effect of oral Quma Tongluo decoction on oxaliplatin-related chronic peripheral neuropathy. Methods: A total of 64 patients who met the inclusion criteria were randomly divided into an experimental group and a control group, with 32 cases in each group. The experimental group took Quma Tongluo decoction granules orally (2 times a day, 1 package each time, morning and evening after meals), and the control group took mecobalamin tablets orally (1 tablet each time, 3 times a day, after meals). After 4 weeks of treatment, the quantitative score of chronic peripheral neuropathy severity, a quantitative score of numbness, a quantitative score of pain, a chemotherapeutic peripheral neurotoxicity score, comprehensive neuropathy score, peripheral neurotoxicity grade, KPS score, and neuropathy area range score were compared between the two groups before and after treatment. Results: Before treatment, there were no significant differences between the two groups in the quantitative score of chronic peripheral neuropathy severity, quantitative score of numbness, chemotherapeutic peripheral neurotoxicity score, total neuropathy score, peripheral neurotoxicity grade, and chronic OIPN symptom range score (P > .05). After 4 weeks of treatment, there were significant differences in the quantitative score of chronic peripheral neuropathy severity, quantitative score of numbness, chemotherapeutic peripheral neurotoxicity score, total neuropathy score, peripheral neurotoxicity grade, and chronic OIPN symptom range score between the two groups (P < .05). There was no significant difference in pain quantification score and KPS score between the two groups before and after treatment (P > .05). The total effective rate of Quma Tongluo decoction in the treatment of oxaliplatin-related chronic peripheral neuropathy was higher than that of mecobalamin (87.1% > 20.6%), and no obvious adverse reactions such as Gastrointestinal reactions and allergic reactions were observed.One patient in the experimental group had diarrhea, the incidence of adverse reactions was about 3.2%, and the control group had no adverse reactions. Conclusions: Quma Tongluo decoction can effectively treat oxaliplatin-related chronic peripheral neuropathy, reduce the symptoms while reducing the scope of symptoms, and has no obvious adverse reactions in clinical practice, with good safety.

A meta-analysis on the efficacy of vacuum sealing drainage combined with autologous platelet-rich plasma in the treatment of Grade 2 and Grade 3 diabetic foot ulcers.

This meta-analysis aims to systemically evaluate the efficacy of vacuum sealing drainage (VSD) combined with autologous platelet-rich plasma (PRP) in the treatment of diabetic foot ulcers (DFU). The China HowNet, China Biomedical Literature, VIP periodical resource integration service platform, Wanfang, Embase, Cochrane Central, and PubMed databases were retrieved using the computer. The retrieval period was up to July 2021. Randomised controlled trials on VSD combined with PRP in the treatment of DFU were collected. Those trials that met the inclusion criteria were included for meta-analysis using RevMan 5.3 software. A total of 13 articles were included. In the trial group, 477 patients with DFU were treated with VSD combined with PRP, while in the control group, 482 patients with DFU were treated with conventional dressings and/or VSD. The meta-analysis showed that, compared with the control group, VSD combined with PRP has significant advantages in shortening healing time (standardised mean difference [SMD] = -0.87, 95% confidence interval [CI]: -1.07 to -0.67, P < .00001), improving ulcer healing rates (odds ratio = 4.01, 95% CI: 2.95 ~ 5.46, P < .00001), and reducing hospital stays (mean difference = -15.29, 95% CI: -16.05 to -14.54, P < .00001), but the differences in dressing change times (SMD = -1.27, 95% CI: -2.71 to 0.17, P = .08) and hospitalisation expenses (SMD = -0.16, 95% CI: -13.40 to 13.07, P = .98) were not statistically significant. VSD combined with autologous PRP has good curative efficacy in the treatment of DFU and is a better treatment option. However, this treatment is limited in patients with platelet dysfunction, thrombocytopenia, leukaemia, and poor general condition.

Gene expression profiles between cystic and solid vestibular schwannoma indicate susceptible molecules and pathways in the cystic formation of vestibular schwannoma.

Previous research has shown that although NF2 gene mutation is the major cause of vestibular schwannoma (VS), it may not directly participate in cystic VS (CVS). To elucidate the underlying potential genetic mechanisms in the cystic formation of VS, we compared differences in gene expression between solid VS (SVS) and CVS via a bioinformatics analysis. The cDNA microarray method and miRNA sequencing were performed on 29 representative VSs (17 CVSs and 12 SVSs). A differential expression analysis was used to identify differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs). Then, miRNA-mRNA regulatory networks were constructed. Gene ontology (GO), a KEGG pathway enrichment analysis, and the protein-protein interaction (PPI) were used to analyze the co-differentially expressed DEmRNAs at the functional level. From the differential expression analyses, 1304 DEmRNAs, 55 DEmiRNAs, and hub genes including PTEN, FOXO1, FOXO3, VEGFA, and SIRT1 were identified. Histological evidence is presented to confirm the makeup of the hubs, which corresponded with the cDNA microarray. Our analysis revealed that the maps of apoptosis, cellular response to hypoxia, and the PI3K-Akt, AMPK, FOXO, and chemokine signaling pathways were significantly enriched. In addition, the TUNEL assay, immunoblotting analysis, and transmission electron microscope revealed increased degenerative changes in CVS. These findings could be the foundation for understanding the potential role of differential genes in the cystic formation of VS and be helpful in exploring the potential biomarkers for the differential diagnosis, prognosis, and development of drug targets for CVS.

Tumor suppressor HIC1 is synergistically compromised by cancer-associated fibroblasts and tumor cells through the IL-6/pSTAT3 axis in breast cancer.

BACKGROUND: Interleukin-6 (IL-6) is commonly highly secreted in the breast cancer (BrCA) microenvironment and implicated in disease development. In this study, we aimed to determine the role of the IL-6/pSTAT3/HIC1 axis in the breast cancer microenvironment, including in cancer-associated fibroblasts (CAFs) and breast cancer cells. METHODS: Stromal fibroblasts from the breast cancer tissue were isolated, and the supernatants of the fibroblasts were analyzed. Recombinant human IL-6 (rhIL-6) was applied to simulate the effect of CAF-derived IL-6 to study the mechanism of HIC1 (tumor suppressor hypermethylated in cancer 1) downregulation. IL-6 was knocked down in the high IL-6-expressing BrCA cell line MDA-MB-231, which enabled the investigation of the IL-6/pSTAT3/HIC1 axis in the autocrine pathway. RESULTS: Increased IL-6 was found in the supernatant of isolated CAFs, which suppressed HIC1 expression in cancer cells and promoted BrCA cell proliferation. After stimulating the BrCA cell line SK-BR-3 (where IL-6R is highly expressed) with rhIL-6, signal transducers and activators of transcription 3 (STAT3) was found to be phosphorylated and HIC1 decreased, and a STAT3 inhibitor completely rescued HIC1 expression. Moreover, HIC1 was restored upon knocking down IL-6 expression in MDA-MB-231 cells, accompanied by a decrease in STAT3 activity. CONCLUSIONS: These findings indicate that IL-6 downregulates the tumor suppressor HIC1 and promotes BrCA development in the tumor microenvironment through paracrine or autocrine signaling.

Complement depletion and Coombs positivity in pneumococcal hemolytic uremic syndrome (pnHUS). Case series and plea to revisit an old pathogenetic concept.

Hemolytic uremic syndrome is a rare complication of invasive pneumococcal infection (pnHUS). Its pathogenesis is poorly understood, and treatment remains controversial. The emerging role of complement in various forms of HUS warrants a new look at this "old" disease. We performed a retrospective analysis of clinical and laboratory features of three sequential cases of pnHUS since 2008 associated with pneumonia/pleural empyema, two due to Streptococcus pneumoniae serotype 19 A. Profound depletion of complement C3 (and less of C4) was observed in two patients. One patient was Coombs test positive. Her red blood cells (RBCs) strongly agglutinated with blood group compatible donor serum at 0 °C, but not at 37 °C. All three patients were treated with hemodialysis, concentrated RBCs, and platelets. Patient 2 received frozen plasma for hepatic failure with coagulation factor depletion. Intravenous immunoglobulin infusion, intended to neutralize pneumococcal neuraminidase in patient 3, was associated with rapid normalization of platelets and cessation of hemolysis. Two patients recovered without sequelae or disease recurrence. Patient 2 died within 2½ days of admission due to complicating Pseudomonas aeruginosa sepsis and multiorgan failure. Our observations suggest that pnHUS can be associated with dramatic, transient complement consumption early in the course of the disease, probably via the alternative pathway. A critical review of the literature and the reported cases argue against the postulated pathological role of preformed antibodies against the neuraminidase-exposed Thomsen-Friedenreich neoantigen (T antigen) in pnHUS. The improved understanding of complement regulation and bacterial strategies of complement evasion allows to propose a testable, new pathogenetic model of pnHUS. This model shifts emphasis from the action of natural anti-T antibodies toward impaired Complement Factor H (CFH) binding and function on desialylated membranes. Removal of neuraminic acid residues converts (protected) self to non-self surfaces that supports membrane attack complex (MAC) assembly. Complement activation is potentially exacerbated by decreased CFH availability following tight CFH binding to pneumococcal evasion proteins and/or by the presence of genetic variants of complement regulator proteins. Detailed clinical and experimental investigations are warranted to better understand the role of unregulated complement activation in pnHUS. Instead of avoidance of plasma, a new, integrated model is evolving, which may include short-term therapeutic complement blockade, particularly where genetic or functional APC dysregulation is suspected, in addition to bacterial elimination and, potentially, neuraminidase neutralization.

Construction and application of a lung cancer stem cell model: antitumor drug screening and molecular mechanism of the inhibitory effects of sanguinarine.

Lung cancer is a neoplasm with a 5-year survival rate of less than 15 % and a leading cause of death worldwide, despite recent progress in treatment and diagnostic methods. Lung cancer stem-like cells (CSCs) are pivotal in lung cancer metastasis and drug resistance. This study aimed to develop lung CSCs that stably express stem cell properties through transfection to further screen traditional Chinese herbal compounds. Lung adenocarcinoma stem cells, which include various phenotypic subgroups, are normally characterized by high expression levels of pluripotent stem cell genes, particularly Nanog and OCT4. Plasmids containing Nanog and OCT4 were constructed and transfected into cells, and lung CSCs were identified not only in vitro using RT-PCR, Western blotting, plate cloning, sphere formation, drug resistance, and transwell migration but also in vivo using a nude mouse tumorigenicity assay. Subsequently, sanguinarine, which is derived from the whole leaves of the traditional Chinese medicine celandine, was identified through the high-throughput screening of a small-molecule compound library. Investigation of the molecular mechanisms of the effects of sanguinarine revealed that it significantly inhibited lung CSC proliferation, invasion, and apoptosis, possibly via downregulation of the Wnt/ß-catenin signaling pathway. Our results indicate that lung CSCs established by gene transfection may provide a stable and effective method of constructing CSCs to effectively screen potential antitumor drugs. Furthermore, these results suggest that sanguinarine may be a natural antitumor compound that targets lung CSCs, laying a foundation for further clinical study.

Spatial distribution of rare earth elements and their impact factors in an area with a high abundance of regolith-hosted deposits.

Despite the widespread occurrence of regolith-hosted rare earth elements (REEs) across South China, their spatial distribution characteristics in soils and their impact factors remain largely uncertain. This knowledge gap impedes the exploration of regolith-hosted REE deposits and the assessment of the environmental risks associated with REEs. To address this issue, 180 soil samples were collected from Meizhou City, Guangdong Province, a region known for its high abundance of regolith-hosted REEs. Subsequently, the correlations between REE enrichment/fractionation and various factors, i.e., topography, climate conditions, land use, and landform were analysed using the geo-detector method. The results revealed a highly uneven spatial distribution of REEs and their fractionation features with some regions displaying distinct spatial patterns. Elevation was the dominant factor influencing this distribution, and showed strong correlations with the concentrations of REEs, light REEs (LREEs) and heavy REEs (HREEs); the LREE/HREE ratio; and the positive Ce anomaly (δCe). The negative Eu anomaly (δEu) showed a good correlation with rock type. The enrichment and fractionation of REEs indicated a coupling among the abovementioned factors. For REE enrichment, areas with elevations of 138-148 m, precipitation levels of 1553-1574 mm, annual average land surface temperatures of 30.4-30.5 °C, leaf area index values of 22-29 and surface cutting degree of 21.5-29.9 m showed the highest average abundance within each type (scope) of the predominant factors. These findings highlight the key factors affecting REE distribution, thereby aiding the efficient utilization of regolith-hosted REE resources and the evaluation of their environmental risks.

Insights into the formulation of lipid nanoparticles for the optimization of mRNA therapeutics.

mRNA-based therapeutics increasingly demonstrate significant potential in treating various diseases, including infectious diseases, cancers, and genetic disorders. Effective delivery systems are crucial for advancing mRNA therapeutics. Lipid nanoparticles (LNPs) serve as an excellent carrier, widely validated for their safety and tolerability in commercially available mRNA vaccines. Standard LNPs typically consist of four components: ionizable lipids (ILs), helper lipids, cholesterol, and polyethylene glycol-lipids (PEG-lipids), with the structural design of ILs gradually becoming a focal point of research interest. The chemical structures and formulations of the other components also significantly affect the delivery efficiency, targeting specificity, and stability of LNPs. The complex formulations of LNPs may hinder the clinical transformation of mRNA therapeutics and have raised widespread concerns about their safety. This review aims to summarize the progress of LNPs-based mRNA therapeutics in clinical trials, focusing on adverse effects that occurred during these trials. It also discusses representative innovations in LNP components, highlighting challenges and potential ways in this research field. We firmly believe this review will promote further improvements and designs of LNP compositions to optimize mRNA therapeutics. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures.

Transcranial Doppler analysis based on computer and artificial intelligence for acute cerebrovascular disease.

Cerebrovascular disease refers to damage to brain tissue caused by impaired intracranial blood circulation. It usually presents clinically as an acute nonfatal event and is characterized by high morbidity, disability, and mortality. Transcranial Doppler (TCD) ultrasonography is a non-invasive method for the diagnosis of cerebrovascular disease that uses the Doppler effect to detect the hemodynamic and physiological parameters of the major intracranial basilar arteries. It can provide important hemodynamic information that cannot be measured by other diagnostic imaging techniques for cerebrovascular disease. And the result parameters of TCD ultrasonography such as blood flow velocity and beat index can reflect the type of cerebrovascular disease and serve as a basis to assist physicians in the treatment of cerebrovascular diseases. Artificial intelligence (AI) is a branch of computer science which is used in a wide range of applications in agriculture, communications, medicine, finance, and other fields. In recent years, there are much research devoted to the application of AI to TCD. The review and summary of related technologies is an important work to promote the development of this field, which can provide an intuitive technical summary for future researchers. In this paper, we first review the development, principles, and applications of TCD ultrasonography and other related knowledge, and briefly introduce the development of AI in the field of medicine and emergency medicine. Finally, we summarize in detail the applications and advantages of AI technology in TCD ultrasonography including the establishment of an examination system combining brain computer interface (BCI) and TCD ultrasonography, the classification and noise cancellation of TCD ultrasonography signals using AI algorithms, and the use of intelligent robots to assist physicians in TCD ultrasonography and discuss the prospects for the development of AI in TCD ultrasonography.

Impact of lockdown on the growth of children in China aged 3-6 years during the COVID-19 pandemic.

Background: Lockdowns in COVID-19 pandemic led to less physical activity and more intake of unhealthy food in children. The aim of this study was to investigate the negative impact of major lockdowns on the growth of children aged 3-6 years during COVID-19 pandemic period. Methods: Physical examination results in 2019 to 2022 from 5834 eligible children (2972 males and 2862 females) from Southwestern China who were 3 years old in 2019 were retrospectively collected. Height and weight data points were extracted from the results, and percentiles of height (height%), weight (weight%), and BMI (BMI%), and rates of overweight and obesity were calculated and compared between different years during the pandemic. Results: After analyzing the 15404 growth data points from 5834 children, a slowly increasing trend of height% from 2019 to 2022 was observed. Weight%, BMI%, overweight rate, obesity rate, and combined overweight and obesity rate had two peaks in 2020 and 2022 when major lockdowns were adopted and a drop in between (year 2021), except for obesity rate which did not drop in 2021. Similar results were shown after stratification by gender. Conclusion: The lockdowns in COVID-19 pandemic promoted obesity of kindergarten children, but did not show any negative impact on their height growth possibly due to over-nutrition of children during lockdowns. More efforts need to be made to limit the increase of obesity rate in kindergarten children during possible future lockdowns.

Wogonin Ameliorated Obesity-Induced Lipid Metabolism Disorders and Cardiac Injury via Suppressing Pyroptosis and Deactivating IL-17 Signaling Pathway.

Obesity leads to structural and functional changes in the heart and has become a global burden of disease. Wogonin is a natural flavonoid which possesses cardioprotective, neuroprotective, and anti-cancer properties. However, the effects of wogonin on obesity-induced cardiac injury remain unclear. In this study, the high-fat diet (HFD)-induced obese mice model was successfully established. Moreover, HFD induced a fat mass and cardiac injury in mice. More importantly, wogonin treatment reduced fat mass and improved cardiac function of HFD mice. Consistently, wogonin ameliorated myocardial lipid metabolism in HFD-induced obese mice by reducing triglyceride (TC), total cholesterol (TG), and non-esterified fatty acid (NEFA) levels in serum, as well as the TG and free fatty acids (FFA) levels in heart tissues. Interestingly, wogonin treatment alleviated myocardial pyroptosis in HFD-induced obese mice. Through bioinformatic analysis, the IL-17 signaling pathway was predicted to be modulated by wogonin. Results showed that wogonin deactivated the IL-17 signaling pathway in HFD mice. These findings suggested that wogonin ameliorated obesity-induced disorders of lipid metabolism and cardiac injury via suppressing pyroptosis and deactivating the IL-17 signaling pathway, which provided a novel therapeutic strategy for HFD-induced cardiac injury.

Early prelingual auditory and language development in children with simultaneous bilateral and unilateral cochlear implants.

Purpose: This current study aimed to explore early prelingual auditory development (EPLAD) and early language development in Mandarin-speaking children who received simultaneous bilateral cochlear implants (BICI) during the first year of cochlear implantation and compare the performance of the children who received BICI with those received unilateral cochlear implant (UCI). Methods: 39 Mandarin-speaking children who received BICIs simultaneously and 36 children with UCIs were enrolled in this study. To access the EPLAD, the Infant-Toddler Meaningful Auditory Integration Scale (IT/MAIS) was conducted, and a subtest of the simplified short-form version of the Mandarin Communicative Development Inventory (SSF-MCDI) was used to evaluate the development of expressive and receptive vocabulary for the children at indicated time points after surgery. Results: In both the simultaneous BICI and UCI groups, we observed significantly increased scores of the SSF-MCDI and IT/MAIS 1 year after the surgery. There are indications of early advantages in children with BICI in IT/MAIS scores (at 1, 3, and 6 months after activation). For early development of language, a great difference between the expressive vocabulary scores and the receptive vocabulary scores was observed in both groups. We found there were not significant differences between the two groups on expressive or receptive vocabulary scores, the use of more differentiated measures might be required in future research. We further found that the development of the receptive or expressive vocabulary is dramatically correlated with the age at implantation and the total scores of IT/MAIS for children with simultaneous BICIs. Conclusion: These results may supplement the skills development of early language and auditory in Mandarin-native children with simultaneous CIs. It is obvious that children with normal hearing have mastery of receptive vocabulary before that of expressive vocabulary, which is the same as children with unilateral and bilateral CIs in this research. IT/MAIS total scores and age at CI were important factors for early language performance in children with simultaneous BICIs.

Nerve Stimulation by Triboelectric Nanogenerator Based on Nanofibrous Membrane for Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating and common neurological disorder that is difficult to treat. The pain can sustain for many years, making the sufferer extremely painful. Nerve stimulation was first reported half a century ago as a treatment for neuropathic pain. Since then, the method of electrical stimulation through leads placed in the epidural space on the dorsal side of the spinal cord has become a valuable therapeutic tool for SCI. But nerve stimulation equipment is expensive, and the stimulator design and treatment plan are complicated, which hinders its development. In recent years, wearable and implantable triboelectric nanogenerators (TENGs) developed rapidly, and their low cost and safety have brought a new turning point for the development of nerve stimulation. Nanofibrous membrane has been proved that it is a flexible material with the advantages of ultrathin diameter, good connectivity, easy scale-up, tunable wettability, fine flexibility, tunable porosity, controllable composition and so on. In this paper, we discuss the technology of using nanofiber membrane on clothing to create TENGs to provide continuous electrical energy for nerve stimulation to treat SCI in patients by analyzing previous research.

[Diagnostic value of IT-MAIS scores by logistic regression and ROC curve in predicting the degree of hearing loss in infants and toddlers aged 0-36 months].

Objective:This study is inorder to compare the early prelingual auditory development trajectory of infants and toddlers with normal hearing and different degrees of hearing loss, and to explore the value of the Infant-Toddler Meaningful Auditory Integration Scale （IT-MAIS） scores in the diagnosis of hearing loss severity in infants and toddlers aged 0-36 months. Methods:Eight hundred and forty-two cases of infant-toddler from March 2009 to March 2021 were selected as participants, including 231 cases with normal hearing and 611 cases with hearing loss. The IT-MAIS scores of participants with different degrees of hearing loss were fitted with nonlinear regression with age. By respectively constructing three logistic regression models of IT-MAIS total scores, perception scores, discrimination scores and evaluation age, the ROC curve was drawn to evaluate the diagnostic efficacy. Results:The IT-MAIS scores of children with mild, moderate, severe, and profound hearing loss participants changes with age are similar to the development of infants with normal hearing, and they all increase with age. And the more severe the hearing loss, the slower the growth rate, and the lower the peak value that can be reached. The logistic model constructed by combining IT-MAIS total score and evaluation age is the best to distinguish mild and above, moderate and above, severe and above, and profound hearing loss, whose AUC are 0.827, 0.889, 0.948, 0.946. The diagnostic efficiency is the best for infant-toddlers with profound hearing loss, with a sensitivity of 89.6% and a specificity of 88.4%. The more severe the hearing loss, the higher the discrimination accuracy of IT-MAIS and the better the diagnostic efficiency. Conclusion:The logistic model based on the IT-MAIS scale and the ROC curve method have a good efficiency in the diagnosis of hearing loss severity in infants and toddlers aged 0-36 months. When the child cannot cooperate with behavioral audiometry, the results of behavioral audiometry are unreliable, and there is no electrophysiological condition, the IT-MAIS scale is expected to evaluate the degree of infants' hearing loss as an auxiliary tool. It can understand the children's auditory function state more and provides a basis for the subsequent formulation of rehabilitation intervention strategies with certain clinical application value.

Prevalence and Risk Factors of Osteoporosis in Patients with Type 2 Diabetes Mellitus in Nanchang (China): A Retrospective Cohort Study.

Objective: To retrospectively review the clinical data of type 2 diabetes mellitus (T2DM) patients hospitalized in Nanchang, China, summarized the prevalence of osteoporosis (OP) in T2DM patients in this area, and analyzed related influencing factors. Methods: The clinical data of hospitalized patients with T2DM were collected retrospectively. According to the results of bone mineral density test, the subjects were divided into the normal bone mass group, the osteopenia group, and the OP group. Age, gender, educational background, body mass index (BMI), waist-to-hip ratio (WHR), duration of T2DM, glycosylated hemoglobin, serum lipids, and complications of T2DM in the three groups were analyzed and compared. Results: The prevalence of OP in patients with T2DM was 35.77%. There were statistically significant differences in age, gender, BMI, WHR, duration of T2DM, educational background, the level of high-density lipoprotein cholesterol (HDL-C), the prevalence of diabetic retinopathy (DR), and diabetic peripheral neuropathy among the three groups (P < 0.05). Logistic regression analysis showed that increasing age, prolonged duration of T2DM, low BMI, high levels of HDL-C, and complicated DR were risk factors for osteopenia and OP. Conclusion: The prevalence of OP in T2DM was high. Risk factors for abnormal bone mass in T2DM might be females, advanced age, long duration of T2DM, low BMI, high levels of HDL-C, and diabetic microangiopathy.

Clinical and Renal Histology Findings and Different Responses to Induction Treatment Affecting the Long-Term Renal Outcomes of Children With ANCA-Associated Vasculitis: a Single-Center Cohort Analysis.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is relatively rare in children. This article aimed to analyze clinical and renal histology findings and different responses to induction treatment associated with the long-term renal outcomes in children with AAV in a single center. Methods: All pediatric patients with AAV admitted to Tongji Hospital from January 2002 to January 2021 were included in the study. The demographic, clinical, pathological, laboratory, and treatment data and outcomes were collected and analyzed to identify predictors associated with response to induction treatment and progression to end-stage renal disease (ESRD). Results: In total, 48 children with AAV were included in this cohort; 81.25% of them were women, and 91.7% were microscopic polyangiitis (MPA). Kidney involvement was found in 45 patients (93.75%). The most common histopathological subtype was crescentic form in this cohort according to Berden's classification. In total, 34 patients (70.8%) showed eGFR <60 ml/min/1.73 m2 at the time of diagnosis. Complete and partial remission was achieved in 8 patients (16.7%) and 19 patients (39.6%), respectively, following 6-month induction treatment. Half of the patients eventually progressed to ESRD at a mean time of (13.04 ± 15.83) months after diagnosis. The independent predictors of nonremission following induction treatment and progression to ESRD were baseline eGFR <60 ml/min/1.73 m2 and hypertension at diagnosis. Renal survival significantly decreased over time in patients with renal sclerotic subtypes or those with nonremission following induction treatment by Kaplan-Meier curve estimation. Conclusions: Our study demonstrates that women, MPA, and crescentic subtypes are predominant in pediatric AAV in China. Initial renal failure (eGFR <60 ml/min/1.73 m2), hypertension, sclerotic pathological subtype, and nonremission following induction treatment are predictive of long-term renal outcomes.

The Clinical Value of the RA-Adjusted Fracture Risk Assessment Tool in the Fracture Risk Prediction of Patients with Type 2 Diabetes Mellitus in China.

OBJECTIVE: This study aimed to explore the clinical value of the fracture risk assessment tool (FRAX) in the fracture risk prediction of Chinese patients after replacing rheumatoid arthritis (RA) with type 2 diabetes mellitus (T2DM) in the FRAX algorithm. METHODS: A total of 1,047 patients with T2DM from the Endocrinology Department of the Third Affiliated Hospital of Nanchang University were enrolled in this study. Dual-energy X-ray absorptiometry (DXA) was then used to detect their bone density. RA in the FRAX algorithm was replaced with T2DM, and the new RA-adjusted FRAX was used to assess the fracture risk of the patients. RESULTS: The sensitivity, specificity, and Youden's index of the RA-adjusted FRAX to the treatment opinions on T2DM-associated hip fractures were 0.4761, 0.9642, and 0.4403, respectively, while the sensitivity, specificity, and Youden's index of RA-adjusted FRAX to the treatment opinions on T2DM-associated major bone osteoporotic fractures were 0.0080, 1.0000, 0.0080, respectively. The DXA and RA-adjusted FRAX both showed acceptable consistency in the treatment recommendations for hip fractures in patients with T2DM (κ = 0.49) but had poor consistency in treatment recommendations for major bone osteoporotic fractures (κ = 0.010). The body mass index (BMI) scores, femoral neck-bone mineral densities, and number of males in the same treatment opinion group were significantly higher than in the different treatment opinions group (P < 0.001). CONCLUSION: RA-adjusted FRAX is a useful clinical tool for evaluation of hip fracture risk for Chinese patients with T2DM, and the accuracy of fracture risk prediction for male patients with T2DM and patients with T2DM with high BMI scores or high femoral neck-bone mineral density is higher.

VASN promotes proliferation of laryngeal cancer cells via YAP/TAZ.

PURPOSE: To explore whether vasorin protein (VASN) can affect the proliferation of laryngeal cancer cells through the regulation of yes-associated protein (YAP)/TAZ (transcriptional co-activator with PDZ binding motif), and then promote the development of laryngeal cancer. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of VASN in laryngeal carcinoma tissues and different T-stage tumor patients, and the correlation between VASN expression and clinicopathological features was analyzed. The diagnostic value of VASN for laryngeal cancer was assessed by receiver operating characteristic (ROC) analysis. Kaplan-Meier method was used to plot the survival curves of patients with different VASN expression levels. After knocking down VASN in Hep-2 cells or in overexpressing VASN in TU212 cells, cell viability, proliferation ability and protein expression level of YAP/TAZ were detected by cell counting kit-8 (CCK-8), plate cloning assay and Western blot. Furthermore, YAP was overexpressed or knocked down simultaneously to evaluate its effect on the viability and proliferation ability of cells. RESULTS: The expression of VASN in laryngeal carcinoma was significantly higher than that in the normal control group, while, at the same time, the expression of VASN in the t3+t4 tumor patients was significantly higher than that in the t1+t2 tumors. We also found that the expression level of VASN was closely related to N stage, T stage, and lymph node metastasis, suggesting that VASN had a certain diagnostic value for laryngeal cancer. After knocking down VASN in cells, the cell viability, proliferative capacity and YAP/TAZ protein expression level decreased significantly. Besides, overexpressing YAP could reverse the inhibition of cell viability and proliferation ability caused by VASN knockdown. CONCLUSIONS: VASN can promote the development of laryngeal cancer by affecting the expression of YAP/TAZ.

Ramelteon Ameliorates LPS-Induced Hyperpermeability of the Blood-Brain Barrier (BBB) by Activating Nrf2.

The blood-brain barrier (BBB) is important for protecting the brain tissue by selectively exchanging substances between the blood and brain. The integrity of the BBB can be damaged by multiple factors, including oxidative stress and inflammation. Ramelteon is an oral hypnotic drug, and in the present study, we investigated its protective effect on BBB damage, as well as the underlying mechanism. LPS was used to induce BBB damage on mice and stimulate injury on endothelial cells. Evans blue staining assay was used to measure the brain permeability. The expressions of ZO-1 and Occludin were evaluated using immunostaining and Western blot in the brain tissue and endothelial cells, respectively. qRT-PCR and ELISA were used to detect the production of IL-1ß and MCP-1 in the brain vessels. TBA assay was utilized to examine the concentration of MDA in the brain tissue and endothelial cells. The expression of Nrf2 in the nucleus and NQO1 were determined using Western blot assay. The endothelial permeability of the monolayer was examined using the FITC-dextran permeation assay. Firstly, the increased brain permeability and downregulated expression of tight junction proteins in the brain tissue induced by LPS were significantly reversed by treatment with Ramelteon, accompanied by the decrease in the production of IL-1ß and MCP-1 in the vessels in mice. Also, the Nrf2 signaling was activated and oxidative stress in the brain vessels was alleviated by treatment with Ramelteon. Secondly, LPS-induced increase in endothelial monolayer permeability and decrease in tight junction protein expression in bEnd.3 brain endothelial cells were significantly reversed by Ramelteon, accompanied by activated Nrf2 signaling and alleviated oxidative stress. Lastly, the protective effects of Ramelteon against LPS-induced reduction of ZO-1 and Occludin, and the increase in endothelial monolayer permeability were dramatically abolished by silencing Nrf2. Ramelteon might ameliorate LPS-induced hyperpermeability of the BBB by activating the Nrf2 signaling pathway.