Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysis.

BACKGROUND: Sepsis is a high mortality disease which seriously threatens human life and health, for which the pathogenetic mechanism still unclear. There is increasing evidence showed that immune and inflammation responses are key players in the development of sepsis pathology. LncRNAs, which act as ceRNAs, have critical roles in various diseases. However, the regulatory roles of ceRNA in the immunopathogenesis of sepsis have not yet been elucidated. RESULTS: In this study, we aimed to identify immune biomarkers associated with sepsis. We first generated a global immune-associated ceRNA (IMCE) network based on data describing interactions pairs of gene-miRNA and miRNA-lncRNA. Afterward, we excavated a dysregulated sepsis immune-associated ceRNA (SPIMC) network from the global IMCE network by means of a multi-step computational approach. Functional enrichment indicated that lncRNAs in SPIMC network have pivotal roles in the immune mechanism underlying sepsis. Subsequently, we identified module and hub genes (CD4 and STAT4) via construction of a sepsis immune-related PPI network. Then, we identified hub genes based on the modular structure of PPI network and generated a ceRNA subnetwork to analyze key lncRNAs associated with sepsis. Finally, 6 lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) that identified as immune biomarkers of sepsis. Moreover, the CIBERSORT algorithm and the infiltration of circulating immune cells types were performed to identify the inflammatory state of sepsis. Correlation analyses between immune cells and sepsis immune biomarkers showed that the LINC00265 was strongly positive correlated with the macrophages M2 (r = 0.77). CONCLUSION: Collectively, these results may suggest that these lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) played important roles in the immune pathogenesis of sepsis and provide potential therapeutic targets for further researches on immune therapy treatment in patients with sepsis.

Transcriptome-wide identification and characterization of genes exhibit allele-specific imprinting in maize embryo and endosperm.

BACKGROUND: Genomic imprinting refers to a subset of genes that are expressed from only one parental allele during seed development in plants. Studies on genomic imprinting have revealed that intraspecific variations in genomic imprinting expression exist in naturally genetic varieties. However, there have been few studies on the functional analysis of allele-specific imprinted genes. RESULTS: Here, we generated three reciprocal crosses among the B73, Mo17 and CAU5 inbred lines. Based on the transcriptome-wide analysis of allele-specific expression using RNA sequencing technology, 305 allele-specific imprinting genes (ASIGs) were identified in embryos, and 655 ASIGs were identified in endosperms from three maize F1 hybrids. Of these ASIGs, most did not show consistent maternal or paternal bias between the same tissue from different hybrids or different tissues from one hybrid cross. By gene ontology (GO) analysis, five and eight categories of GO exhibited significantly higher functional enrichments for ASIGs identified in embryo and endosperm, respectively. These functional categories indicated that ASIGs are involved in intercellular nutrient transport, signaling pathways, and transcriptional regulation of kernel development. Finally, the mutation and overexpression of one ASIG (Zm305) affected the length and width of the kernel. CONCLUSION: In this study, our data will be helpful in gaining further knowledge of genes exhibiting allele-specific imprinting patterns in seeds. The gain- and loss-of-function phenotypes of ASIGs associated with agronomically important seed traits provide compelling evidence for ASIGs as crucial targets to optimize seed traits in crop plants.

Comparison of endotracheal aspirate and bronchoalveolar lavage fluid metagenomic next-generation sequencing in severe pneumonia: a nested, matched case-control study.

OBJECTIVES: To compare clinical outcomes in patients with severe pneumonia according to the diagnostic strategy used. METHODS: In this retrospective, nested, case-control study, patients with severe pneumonia who had undergone endotracheal aspirate (ETA) metagenomic next-generation sequencing of (mNGS) testing (n = 53) were matched at a ratio of 1 to 2 (n = 106) by sex, age, underlying diseases, immune status, disease severity scores, and type of pneumonia with patients who had undergone bronchoalveolar lavage fluid (BALF) mNGS. The microbiological characteristics and patient's prognosis of the two groups were compared. RESULTS: An overall comparison between the two groups showed no significant differences in bacterial, fungal, viral, or mixed infections. However, subgroup analysis of 18 patients who received paired ETA and BALF mNGS showed a complete agreement rate for the two specimens of 33.3%. There were more cases for whom targeted treatment was initiated (36.79% vs. 22.64%; P = 0.043) and fewer cases who received no clinical benefit after mNGS (5.66% vs. 15.09%; P = 0.048) in the BALF group. The pneumonia improvement rate in the BALF group was significantly higher than in the ETA group (73.58% vs. 87.74%, P = 0.024). However, there were no significant differences in ICU mortality or 28-day mortality. CONCLUSIONS: We do not recommend using ETA mNGS as the first-choice method for analyzing airway pathogenic specimens from severe pneumonia patients.

A modified PLASMIC score including the lactate dehydrogenase/the upper limit of normal ratio more accurately identifies Chinese thrombotic thrombocytopenic purpura patients than the original PLASMIC score.

BACKGROUND: The PLASMIC score was recently published to aid in the early identification of thrombotic thrombocytopenic purpura (TTP) patients. This study aims to evaluate whether this score is suitable for Chinese suspected TTP patients and find the utility of patients' other characteristics in predicting severe ADAMTS13 deficiency. METHODS: We retrospectively studied a Chinese cohort of 38 consecutive hospitalized patients with suspected TTP, ADAMTS13 test results, and other clinical data from September 2016 to May 2018. The predictive power of PLASMIC score in our cohort was evaluated, and patients' other characteristics, especially the high lactate dehydrogenase/the upper limit of normal (LDH/ULN), were studied to determine their distinguishing ability for TTP patients. RESULTS: In this Chinese cohort, 17 patients were diagnosed with TTP according to ADAMTS13 activity results. When dichotomized at intermediate-high risk (scores 5-7) vs low risk (scores 0-4), the PLASMIC score predicted TTP with a sensitivity of 100%, a specificity of 9.52%, and a misdiagnosis rate of 90.48%. And the LDH/ULN alone, or plus platelet count, reticulocyte percentage and indirect bilirubin (IBIL) both had excellent predictive power (area under the curve [AUC] 0.937, 95% confidence interval [CI] 0.863-1.000, P = .000, and AUC 0.994, 95% CI 0.980-1.000, P = .000, respectively). The model including platelet count, reticulocyte percentage, IBIL, and LDH/ULN ratio had a sensitivity of 100%, a specificity of 95.2%, and a misdiagnosis rate of 4.8%. CONCLUSIONS: A modified PLASMIC score plus LDH/ULN ratio might be more suitable for identifying ADAMTS13 deficiency patients, especially for making an earlier diagnosis, guiding the immediate and reasonable plasma exchange, and also avoiding unnecessary allocation of plasma.

Trans-vaccenic acid inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cells via a mitochondrial-mediated apoptosis pathway.

BACKGROUND: Intake of trans fatty acids (TFAs) from partially hydrogenated vegetable oil is associated with a variety of adverse outcomes, but little is known about the health effects of ruminant trans fats. Trans-vaccenic acid (TVA) is a naturally occurring TFA found in the fat of ruminants and in human dairy products. The present study was conducted to investigate the anticancer activity and underlying mechanisms of TVA on human nasopharyngeal carcinoma (NPC) 5-8F and CNE-2 cells. METHODS: A CCK8 assay was used to determine the effect of TVA and the Mcl-1 inhibitor S63845 on the proliferation of NPC cells. Apoptosis was measured using flow cytometry. Western blotting was used to detect the protein expression levels of factors associated with Bcl-2-family protein signaling and Akt signaling. RESULTS: TVA significantly inhibited cell proliferation in a dose-dependent manner. Mechanistic investigation demonstrated that TVA significantly decreased p-Akt levels and Bad phosphorylation on Ser-136 and Ser-112. More importantly, we discovered that the Mcl-1 inhibitor S63845 synergistically sensitized NPC cells to apoptosis induction by TVA. CONCLUSION: TVA can inhibit NPC cell growth and induced apoptosis through the inhibition of Bad/Akt phosphorylation. The combined use of TVA and Mcl-1 inhibitors offers a potential advantage for nasopharyngeal cancer treatment.

ABT-199-mediated inhibition of Bcl-2 as a potential therapeutic strategy for nasopharyngeal carcinoma.

BACKGROUND: Aberrant overexpression of Bcl-2 protein has been detected in 80% of nasopharyngeal carcinoma (NPC), and Bcl-2 family proteins are implicated in both NPC oncogenesis and chemotherapy resistance. Previous studies have shown that while treatment of NPC cells with Bcl-2 family inhibitors alone is rarely effective, concomitant treatment with a cytotoxic reagent such as cisplatin can increase efficacy through a synergistic effect. The aim of the current work was to determine how we might increase the efficacy of Bcl-2 family inhibitors in the absence of cytotoxic reagents, which are associated with negative side effect profiles. METHODS: We assessed cell proliferation in Bcl-2 high-expressing NPC cells by CCK-8 assay after treatment with the Bcl-2 inhibitor ABT-199 and/or the Mcl-1 inhibitor S63845. Apoptotic induction by ABT-199 was evaluated by Annexin V-FITC and PI double staining. We also evaluated Bcl-2 family protein expression (Bim, Mcl-1, Bcl-xL, Noxa) after treatment with ABT-199 by western blotting. Finally, xenografted Balb/c nude mice were used to test ABT-199 efficacy in vivo, H&E and immunohistochemistry assay were used to analyze tumor samples. RESULTS: ABT-199 effectively induced NPC cell apoptosis in vitro and in the xenograft model. Following ABT-199 treatment in NPC cells, upregulation of Mcl-1 and Bcl-xL can lead to drug resistance, while concomitant Noxa overexpression partially neutralized the Mcl-1-caused resistance. Given that ABT-199 induces apoptosis in NPC cells through the Bcl-2/Noxa/Mcl-1 axis, treatment avenues further targeting this pathway should be promising. Indeed, the newly developed Mcl-1 inhibitor S63845 in combination with ABT-199 had a synergistic effect on NPC cell apoptosis. CONCLUSION: Bcl-2 inhibition in NPC cells with ABT-199 triggers apoptosis through the Bcl-2/Noxa/Mcl-1 axis, and dual inhibition of the anti-apoptotic Bcl-2 family proteins Bcl-2 and Mcl-1 provided a strong synergistic effect without the need for adjunctive cytotoxic agent treatment with cisplatin.

Structures, Phase Transformations, and Dielectric Properties of BiTaO4 Ceramics.

Low (α)- and high-temperature (ß) forms of BiTaO4 have attracted much attention due to their dielectric and photocatalytic properties. In the present work, a third form, the so-called HP-BiTaO4, was synthesized at high temperature and pressure. The phase evolution, phase transformations, and dielectric properties of α- and ß-BiTaO4 and HP-BiTaO4 ceramics are studied in detail. ß-BiTaO4 ceramics densified at 1300 °C with the microwave permittivity εr ≈ 53, the microwave quality factor Qf ≈ 12070 GHz, and the temperature coefficient of resonant frequency τf ≈ -200 ppm/°C. HP-BiTaO4 ceramics were synthesized at 5 GPa and 1300 °C followed by annealing at 600 °C. In contrast with the α phase, HP-BiTaO4 exhibited εr ≈ 195 at 1 kHz to 10 MHz, accompanied by a low dielectric loss of ∼0.004. The relation between structure and dielectric properties is discussed in the context of Shannon's additive rule and bond theory.

[Expression, Purification and Bioinformatics Analysis of ß-hexosaminidase of Dermatophagoides farinae].

The DNA fragment encoding ß-hexosaminidase was synthesized, and cloned into pET-28a vector. The constructed plasmid pMD18-T-ß-hexosaminidase was transformed into E. coli Top 10 and followed by expression of the protein induced by IPTG. SDS-PAGE result showed that the relative molecular mass of the recombinant protein was about M, 55 000. The full length of ß-hexosaminidase gene was 1 410 bp. Bioinformatics analysis revealed that ß-hexosaminidase was composed with 469 amino acid residues with a calculated molecular weight of Mr 55,000, and its secondary structure was composed of strand (14.71%), helix (30.70%), and loop (54.58%). ß-hexosaminidase was a hydrophilic protein without signal peptide, and located in the extracellular space.

Study on characteristics of wideband acoustic immittance in patients with Inner Ear Malformations.

OBJECTIVE: To compare the differences in wideband absorbance and the resonance frequency (RF) between patients with inner ear malformations and normal control, and to explore the auditory diagnostic value of wideband acoustic immittance (WAI). METHODS: A total of 38 patients (59 ears) with enlarged vestibular aqueduct (EVA), 13 patients (14 ears) with incomplete partition type I (IP-I) and 13 patients (26 ears) with incomplete partition type II (IP-II) were included. 50 normal control (100 ears). All subjects underwent WAI tests to compare the absorbance configuration and resonance frequency. RESULTS: All the group showed lower absorbance at ambient pressure than at peak pressure in certain frequencies under 2000Hz. Under 1000Hz, the absorbance of EVA was higher than that of other groups. The average absorbance and highest absorbance of IP-I were the lowest(P＜0.05). However, IP-II and normal group had similarity on some characteristics. The three IEM groups mainly different at low and high frequencies, but not at medium frequencies. The highest absorbance of all the groups were appeared around 3000Hz. The RF of all the groups from low to high were EVA＜IP-II＜normal control＜IP-I, and the lowest was EVA(P＜0.05). CONCLUSION: Inner ear malformations can affect energy absorbance and RF. WAI is sensitive and non-invasive to provide useful information about inner ear status and facilitate detection of ear pathology.

Smart Nanoplatforms Responding to the Tumor Microenvironment for Precise Drug Delivery in Cancer Therapy.

The tumor microenvironment (TME) is a complex and dynamic entity, comprising stromal cells, immune cells, blood vessels and extracellular matrix, which is intimately associated with the occurrence and development of cancers, as well as their therapy. Utilizing the shared characteristics of tumors, such as an acidic environment, enzymes and hypoxia, researchers have developed a promising cancer therapy strategy known as responsive release of nano-loaded drugs, specifically targeted at tumor tissues or cells. In this comprehensive review, we provide an in-depth overview of the current fundamentals and state-of-the-art intelligent strategies of TME-responsive nanoplatforms, which include acidic pH, high GSH levels, high-level adenosine triphosphate, overexpressed enzymes, hypoxia and reductive environment. Additionally, we showcase the latest advancements in TME-responsive nanoparticles. In conclusion, we thoroughly examine the immediate challenges and prospects of TME-responsive nanopharmaceuticals, with the expectation that the progress of these targeted nanoformulations will enable the exploitation, overcoming or modulation of the TME, ultimately leading to significantly more effective cancer therapy.

ITPR1 variant-induced autosomal dominant hereditary spastic paraplegia in a Chinese family.

Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disease prominently characterized by slowly progressive lower limb weakness and spasticity. The significant genotypic and phenotypic heterogeneity of this disease makes its accurate diagnosis challenging. In this study, we identified the NM_001168272: c.2714A > G (chr3.hg19: g.4716912A > G, N905S) variant in the ITPR1 gene in a three-generation Chinese family with multiple individuals affected by HSP, which we believed to be associated with HSP pathogenesis. To confirm, we performed whole exome sequencing, copy number variant assays, dynamic mutation analysis of the entire family, and protein structure prediction. The variant identified in this study was in the coupling domain, and this is the first corroborated report assigning ITPR1 variants to HSP. These findings expand the clinical and genetic spectrum of HSP and provide important data for its genetic analysis and diagnosis.

Prevention of urinary tract infection using a silver alloy hydrogel-coated catheter in critically ill patients: A single-center prospective randomized controlled study.

Background: A new type of silver alloy hydrogel-coated (SAH) catheter has been shown to prevent bacterial adhesion and colonization by generating a microcurrent, and to block the retrograde infection pathway. However, these have only been confirmed in ordinary patients. This study aims to evaluate the effectiveness of a SAH catheter for preventing urinary tract infections in critically ill patients. Methods: This was a prospective single-center, single-blind, randomized, controlled study. A total of 132 patients requiring indwelling catheterization in the intensive care unit (ICU) of the First Affiliated Hospital of the University of Science and Technology of China between October 2022 and February 2023 and who met the study inclusion/exclusion criteria were randomly divided into two groups. Patients in the SAH catheter group received a SAH catheter, while patients in the conventional catheter group received a conventional siliconized latex Foley catheter. The main outcome measure was the incidence of catheter-associated urinary tract infections (CAUTIs). Secondary outcome indicators included urine positivity for white blood cells and positive urine cultures on 3 days, 7 days, 10 days, and 14 days after catheterization, number of viable bacteria in the catheter biofilm on day 14, pathogenic characteristics of positive urine cultures, length of ICU stay, overall hospital stay, ICU mortality, and 28-day mortality. All the data were compared between the two groups. Results: A total of 68 patients in the conventional catheter group and 64 patients in the SAH catheter group were included in the study. On day 7 after catheter placement, the positivity rate for urinary white blood cells was significantly higher in the conventional catheter group than in the SAH catheter group (33.8% vs. 15.6%, P=0.016). On day 10, the rates of positive urine cultures (27.9% vs. 10.9%, P=0.014) and CAUTIs (22.1% vs. 7.8%, P=0.023) were significantly higher in the conventional catheter group than in the SAH catheter group. On day 14, the numbers of viable bacteria isolated from the catheter tip ([3.21±1.91]×106 colony-forming units [cfu]/mL vs. [7.44±2.22]×104 cfu/mL, P <0.001), balloon segment ([7.30±1.99]×107 cfu/mL vs. [3.48±2.38]×105 cfu/mL, P <0.001), and tail section ([6.41±2.07]×105 cfu/mL vs. [8.50±1.46]×103 cfu/mL, P <0.001) were significantly higher in the conventional catheter group than in the SAH catheter group. The most common bacteria in the urine of patients in both groups were Escherichia coli (n=13) and Pseudomonas aeruginosa (n=6), with only one case of Candida in each group. There were no significant differences between the two groups in terms of ICU hospitalization time, total hospitalization time, ICU mortality, and 28-day mortality. Conclusion: SAH catheters can effectively inhibit the formation of catheter-related bacterial biofilms in critically ill patients and reduce the incidence of CAUTIs, compared with conventional siliconized latex Foley catheters; however, regular replacement of the catheter is still necessary.

TMEM52B Isoforms P18 and P20 Differentially Promote the Oncogenesis and Metastasis of Nasopharyngeal Carcinoma.

Transmembrane protein 52B (TMEM52B), a newly identified tumor-related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B-P18 and TMEM52B-P20, differing in their N-terminals. While both isoforms exhibit similar pro-oncogenic roles and contribute to drug resistance in NPC, TMEM52B-P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B-P18 is confined to the cytoplasm, while TMEM52B-P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane-localized TMEM52B-P20 promotes E-cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B-P18 and TMEM52B-P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis.

Inhibition of Toll-like receptor-mediated inflammation in vitro and in vivo by a novel benzoxaborole.

Pro-inflammatory cytokines play a critical role in the development of autoimmune and inflammatory diseases. Targeting the cytokine environment has proven efficient for averting inflammation. In this study, we reported that 6-[4-(aminomethyl)-2-chlorophenoxyl]benzo[c][1,2]oxaborol-1(3H)-ol (AN3485), a benzoxaborole analog, inhibited TLR2-, TLR3-, TLR4-, and TLR5-mediated TNF-α, IL-1ß, and IL-6 release from human PBMCs and isolated monocytes with IC(50) values ranging from 18 to 580 nM, and the inhibition was mediated at the transcriptional level. Topical administration of AN3485 significantly reduced PMA-induced contact dermatitis and oxazolone-induced delayed-type hypersensitivity in mice, indicating its capability of penetrating skin and potential topical application in skin inflammation. Oral administration of AN3485 showed dose-dependent suppression of LPS-induced TNF-α and IL-6 production in mice with an ED(90) of 30 mg/kg. Oral AN3485, 35 mg/kg, twice a day, suppressed collagen-induced arthritis in mice over a 20-day period. The potent anti-inflammatory activity in in vitro and in vivo disease models makes AN3485 an attractive therapeutic lead for a variety of cutaneous and systemic inflammatory diseases.

Diagnostic Value and Clinical Application of Metagenomic Next-Generation Sequencing for Infections in Critically Ill Patients.

Objective: To evaluate the diagnostic value and clinical application of metagenomic next-generation sequencing (mNGS) for infections in critically ill patients. Methods: Comparison of diagnostic performance of mNGS and conventional microbiological testing for pathogens was analyzed in 234 patients. The differences between immunocompetent and immunocompromised individuals in mNGS-guided anti-infective treatment adjustment were also analyzed. Results: The sensitivity and specificity of mNGS for bacterial and fungal detection were 96.6% (95% confidence interval [CI], 93.5%-99.6%) and 83.1% (95% CI, 75.2%-91.1%), and 85.7% (95% CI, 71.9%-99.5%) and 93.2% (95% CI, 89.7%-96.7%), respectively. Overall, 152 viruses were detected by mNGS, but in which 28 viruses were considered causative agents. The proportion of mNGS-guided beneficial anti-infective therapy adjustments in the immunocompromised group was greater than in the immunocompetent group (48.5% vs 30.1%; P=0.008). In addition, mNGS-guided anti-infective regimens with peripheral blood and BALF specimens had the highest proportion (39.0%; 40.0%), but the proportion of patients not helpful due to peripheral blood mNGS was also as high as 22.0%. Conclusion: mNGS might be a promising technology to provide precision medicine for critically ill patients with infection.

Audiological characteristics and cochlear implant outcome in children with cochlear nerve deficiency.

Objectives: This study aimed to examine the audiological characteristics and validity of predicting outcomes of cochlear implants (CIs) in children with cochlear nerve deficiency (CND) based on the internal auditory meatus (IAM) nerve grading system. Methods: The audiological characteristics of 188 ears in 105 children diagnosed with CND were analyzed based on the IAM nerve grading system. In addition, 42 children with CND who underwent CI were also divided into four groups based on the system, and their auditory and speech performance at baseline (preoperative) and 6, 12, and 24 months after CI were analyzed and compared with those of the control group (n = 24) with a normal cochlear nerve (CN) and CI. Results: The audiological test results showed no significant differences among the four CND groups in terms of elicited rates of distortion product otoacoustic emission (DPOAE) (p = 1.000), auditory brainstem response (ABR) (p = 0.611), and cochlear microphonic (CM) (p = 0.167). Hearing in the CND IV group was significantly better than that in the CND I group (p < 0.05). In children with CI, the auditory and speech performance of the control group was significantly higher than all CND groups from 6 to 24 months (p < 0.05) and 12 to 24 months (p < 0.05), respectively. Meanwhile, there were no significant differences between each pair group in the four CND groups (p > 0.05). Conclusion: Children with CND, including those in whom the CN was not visualized by MRI, can benefit from CI. Additionally, the IAM nerve grading system could not predict the outcomes of CI in children with CND.

[Perioperative management of cochlear implantation for CHARGE syndrome].

Objective:To explore the perioperative period characteristics of paediatric cochlear implant recipients of CHARGE syndrome with complex deformities. Methods:Retrospective case series of CHARGE syndrome were included. Radiological results, intraoperative findings, surgical planning and post-operative complications were analyzed. Routine audiometric measurements, speech perception categories and speech intelligibility ratings were performed pre and post-operatively to measure auditory speech rehabilitation outcomes. Results:Five prelingual profoundly deaf children were identified, aged from 14 months to 60 months. All patients had congenital heart disease and underwent surgery before cochlear implantation. Upper airway abnormalities were detected as choanal atresia, laryngomalacia and tracheal stenosis. All ten ears showed cochlear abnormalities（Incomplete partition Ⅱ）, eight of them combined with secretory otitis media and/or middle ear deformity. All patients underwent single side surgery using standard transmastoid facial recess approach. Full insertion of the electrode was achieved in two cochleas, while partial insertion was done in three cochleas. Three ears with absent auditory nerves in MRI showed no response in the neural remote test. All patients had improved audio-speech performance with CAP scores 3.0±0.7 and 3.6±0.9, SIR scores 1.2±0.4 and 1.8±0.8, IT-MAIS scores 18.8±9.1 and 26.2±10.0, MUSS scores 2.2±2.4 and 7.2±8.3 after twelve months and twenty-four months follow up. Conclusion:Cochlear implantation in patients with CHARGE syndrome is a challenge in both its surgical and rehabilitation aspects due to multiple abnormalities. Adequate treatment planning is necessary for safe and effective surgery, including airway structures and intricate temporal bone landmarks.

Effects of aging on ocular vestibular-evoked myogenic potential using ER-3A insert earphone and B81 bone vibrator.

Purpose: Aging is a process associated with degeneration and dysfunction of peripheral vestibular system or apparatus. This study aimed to investigate the influence of aging on ocular vestibular-evoked myogenic potential (oVEMP) response rates and recording parameters using the B81 bone vibrator and compare them with air conduction stimuli (ACS) oVEMP response characteristics. Methods: In 60 healthy participants aged 10-71 years (mean age 39.9; 29 male participants), the oVEMP response was elicited using a B81 bone vibrator and an ER-3A insert earphone. The effects of age and stimulus on oVEMP response rates and recording parameters were evaluated. Results: Response rates and amplitudes declined with aging using either ACS or bone-conducted vibration (BCV) stimulation, particularly in individuals over 60 years of age, whereas thresholds increased and N1 latencies were prolonged. BCV showed fewer risks of absent oVEMP response than ACS (p = 0.002). BCV acquired higher amplitudes (p < 0.001), lower thresholds, and shorter N1 and P1 latencies (all p < 0.001) than ACS. Conclusions: The absence of an oVEMP response may be attributed to aging rather than a concurrent vestibular disorder. B81-BCV likely produces higher mechanical drives to the vestibular hair cells at safer and non-traumatic levels compared with ACS and therefore may be more likely to evoke a response in the elderly cohort, whose vestibular function and mechanical sensitivity have declined. Thus, B81-BCV stimulation is more effective and safer to elicit oVEMPs, and it should be recommended when ACS fails in the clinic, particularly in the elderly population.

FGF-2 signaling in nasopharyngeal carcinoma modulates pericyte-macrophage crosstalk and metastasis.

Molecular signaling in the tumor microenvironment (TME) is complex, and crosstalk among various cell compartments in supporting metastasis remains poorly understood. In particular, the role of vascular pericytes, a critical cellular component in the TME, in cancer invasion and metastasis warrants further investigation. Here, we report that an elevation of FGF-2 signaling in samples from patients with nasopharyngeal carcinoma (NPC) and xenograft mouse models promoted NPC metastasis. Mechanistically, tumor cell-derived FGF-2 strongly promoted pericyte proliferation and pericyte-specific expression of an orphan chemokine (C-X-C motif) ligand 14 (CXCL14) via FGFR1/AHR signaling. Gain- and loss-of-function experiments validated that pericyte-derived CXCL14 promoted macrophage recruitment and polarization toward an M2-like phenotype. Genetic knockdown of FGF2 or genetic depletion of tumoral pericytes blocked CXCL14 expression and tumor-associated macrophage (TAM) infiltration. Pharmacological inhibition of TAMs by clodronate liposome treatment resulted in a reduction of FGF-2-induced pulmonary metastasis. Together, these findings shed light on the inflammatory role of tumoral pericytes in promoting TAM-mediated metastasis. We provide mechanistic insight into an FGF-2/FGFR1/pericyte/CXCL14/TAM stromal communication axis in NPC and propose an effective antimetastasis therapy concept by targeting a pericyte-derived inflammation for NPC or FGF-2hi tumors.

Comprehensive bulk and single-cell transcriptome profiling give useful insights into the characteristics of osteoarthritis associated synovial macrophages.

Background: Osteoarthritis (OA) is a common chronic joint disease, but the association between molecular and cellular events and the pathogenic process of OA remains unclear. Objective: The study aimed to identify key molecular and cellular events in the processes of immune infiltration of the synovium in OA and to provide potential diagnostic and therapeutic targets. Methods: To identify the common differential expression genes and function analysis in OA, we compared the expression between normal and OA samples and analyzed the protein-protein interaction (PPI). Additionally, immune infiltration analysis was used to explore the differences in common immune cell types, and Gene Set Variation Analysis (GSVA) analysis was applied to analyze the status of pathways between OA and normal groups. Furthermore, the optimal diagnostic biomarkers for OA were identified by least absolute shrinkage and selection operator (LASSO) models. Finally, the key role of biomarkers in OA synovitis microenvironment was discussed through single cell and Scissor analysis. Results: A total of 172 DEGs (differentially expressed genes) associated with osteoarticular synovitis were identified, and these genes mainly enriched eight functional categories. In addition, immune infiltration analysis found that four immune cell types, including Macrophage, B cell memory, B cell, and Mast cell were significantly correlated with OA, and LASSO analysis showed that Macrophage were the best diagnostic biomarkers of immune infiltration in OA. Furthermore, using scRNA-seq dataset, we also analyzed the cell communication patterns of Macrophage in the OA synovial inflammatory microenvironment and found that CCL, MIF, and TNF signaling pathways were the mainly cellular communication pathways. Finally, Scissor analysis identified a population of M2-like Macrophages with high expression of CD163 and LYVE1, which has strong anti-inflammatory ability and showed that the TNF gene may play an important role in the synovial microenvironment of OA. Conclusion: Overall, Macrophage is the best diagnostic marker of immune infiltration in osteoarticular synovitis, and it can communicate with other cells mainly through CCL, TNF, and MIF signaling pathways in microenvironment. In addition, TNF gene may play an important role in the development of synovitis.