Hotspot mutations in the structured ENL YEATS domain link aberrant transcriptional condensates and cancer.

Growing evidence suggests prevalence of transcriptional condensates on chromatin, yet their mechanisms of formation and functional significance remain largely unclear. In human cancer, a series of mutations in the histone acetylation reader ENL create gain-of-function mutants with increased transcriptional activation ability. Here, we show that these mutations, clustered in ENL's structured acetyl-reading YEATS domain, trigger aberrant condensates at native genomic targets through multivalent homotypic and heterotypic interactions. Mechanistically, mutation-induced structural changes in the YEATS domain, ENL's two disordered regions of opposing charges, and the incorporation of extrinsic elongation factors are all required for ENL condensate formation. Extensive mutagenesis establishes condensate formation as a driver of oncogenic gene activation. Furthermore, expression of ENL mutants beyond the endogenous level leads to non-functional condensates. Our findings provide new mechanistic and functional insights into cancer-associated condensates and support condensate dysregulation as an oncogenic mechanism.

Mitochondrial deoxyguanosine kinase is required for female fertility in mice.

Mitochondrial homeostasis plays a pivotal role in oocyte maturation and embryonic development. Deoxyguanosine kinase (DGUOK) is a nucleoside kinase that salvages purine nucleosides in mitochondria and is critical for mitochondrial DNA replication and homeostasis in non-proliferating cells. Dguok loss-of-function mutations and deletions lead to hepatocerebral mitochondrial DNA deletion syndrome. However, its potential role in reproduction remains largely unknown. In this study, we find that Dguok knockout results in female infertility. Mechanistically, DGUOK deficiency hinders ovarian development and oocyte maturation. Moreover, DGUOK deficiency in oocytes causes a significant reduction in mitochondrial DNA copy number and abnormal mitochondrial dynamics and impairs germinal vesicle breakdown. Only few DGUOK-deficient oocytes can extrude their first polar body during in vitro maturation, and these oocytes exhibit irregular chromosome arrangements and different spindle lengths. In addition, DGUOK deficiency elevates reactive oxygen species levels and accelerates oocyte apoptosis. Our findings reveal novel physiological roles for the mitochondrial nucleoside salvage pathway in oocyte maturation and implicate DGUOK as a potential marker for the diagnosis of female infertility.

Efficacy and safety of chloral hydrate in auditory brainstem response test: A systematic review and single-arm meta-analysis.

OBJECTIVES: To evaluate the safety and efficacy of chloral hydrate in auditory brainstem response (ABR) tests. SETTING AND DESIGN: In this study, the authors systematically searched both English (Embase, PubMed, and Web of Science) and Chinese (Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Chinese Science) databases. Two authors independently performed data extraction and quality assessment. The pooled sedation failure rate and the pooled incidence of adverse events were calculated via a random-effects model. Sensitivity and subgroup analyses were performed to explore the sources of heterogeneity, and the PRISMA guideline was followed. PARTICIPANTS: Patients with ABR tests receiving chloral hydrate sedation. MAIN OUTCOME MEASURES: The pooled sedation failure rate and the pooled incidence of adverse events. RESULTS: A total of 23 clinical studies were included in the final analysis. The pooled sedation failure rate of patients who received chloral hydrate sedation before ABR examination was 10.0% [95% confidence interval (CI) (6.7%, 15.0%), I2 = 95%, p < .01]. There were significant differences in the prevalence of sedation failure between sample sizes greater than 200 and those less than or equal to 200 (5.6% vs. 19.6%, p < .01) and between the studies that reported sleep deprivation and those that did not report sleep deprivation (7.1% vs. 18.9%, p < .01). The pooled incidence of adverse events was 10.32% [95% CI (5.83%, 14.82%), I2 = 98.1%, p < .01]. CONCLUSIONS: Chloral hydrate has a high rate of sedation failure, adverse events, and potential carcinogenicity. Therefore, replacing its use in ABR tests with safer and more effective sedatives is warranted.

MiR-146a rs2910164 (G/C) polymorphism is associated with the development and prognosis of acute coronary syndromes: an observational study including case control and validation cohort.

BACKGROUND: Polymorphisms in microRNAs (miRNAs) play an important role in acute coronary syndromes (ACS). The purpose of this study was to assess the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with the development and prognosis of ACS and to explore the underlying mechanisms. METHODS: A case-control study of 1171 subjects was included to determine the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with ACS risk. An additional 612 patients with different miR-146a rs2910164 genotypes, who underwent percutaneous coronary intervention (PCI) were included in the validation cohort and followed for 14 to 60 months. The endpoint was major adverse cardiovascular events (MACE). A luciferase reporter gene assay was used to validate the interaction of oxi-miR-146a(G) with the IKBA 3'UTR. Potential mechanisms were validated using immunoblotting and immunostaining. RESULTS: The miR-146a rs2910164 polymorphism was significantly associated with the risk of ACS (Dominant model: CG + GG vs. CC, OR = 1.270, 95% CI (1.000-1.613), P = 0.049; Recessive model: GG vs. CC + CG, OR = 1.402, 95% CI (1.017-1.934), P = 0.039). Serum inflammatory factor levels were higher in patients with the miR-146a rs2910164 G allele than in those with the C allele. MiR-146a rs2910164 polymorphism in dominant model was associated with the incidence of MACE in post-PCI patients (CG + GG vs. CC, HR = 1.405, 95% CI (1.018-1.939), P = 0.038). However, the miR-34b rs4938723 polymorphism was not associated with the prevalence and prognosis of ACS. The G allele of miR-146a rs2910164 tends to be oxidized in ACS patients. The miRNA fractions purified from monocytes isolated from ACS patients were recognized by the 8OHG antibody. Mispairing of Oxi-miR-146a(G) with the 3'UTR of IKBA results in decreased IκBα protein expression and activation of the NF-κB inflammatory pathway. P65 expression was higher in atherosclerotic plaques from patients carrying the miR-146a rs2910164 G allele. CONCLUSION: The variant of miR-146a rs2910164 is closely associated with the risk of ACS in Chinese Han population. Patients carrying miR-146a rs2910164 G allele may have worse pathological change and poorer post-PCI prognosis, partly due to the oxidatively modified miR-146a mispairing with 3'UTR of IKBA and activating NF-κB inflammatory pathways.

Single-cell multi-omics sequencing reveals chromosome copy number inconsistency between trophectoderm and inner cell mass in human reconstituted embryos after spindle transfer.

STUDY QUESTION: Is the chromosome copy number of the trophectoderm (TE) of a human reconstituted embryos after spindle transfer (ST) representative of the inner cell mass (ICM)? SUMMARY ANSWER: Single-cell multi-omics sequencing revealed that ST blastocysts have a higher proportion of cell lineages exhibiting intermediate mosaicism than conventional ICSI blastocysts, and that the TE of ST blastocysts does not represent the chromosome copy number of ICM. WHAT IS KNOWN ALREADY: Preimplantation genetic testing for aneuploidy (PGT-A) assumes that TE biopsies are representative of the ICM, but the TE and ICM originate from different cell lineages, and concordance between TE and ICM is not well-studied, especially in ST embryos. STUDY DESIGN, SIZE, DURATION: We recruited 30 infertile women who received treatment at our clinic and obtained 45 usable blastocysts (22 from conventional ICSI and 23 reconstituted embryos after ST). We performed single-cell multi-omics sequencing on all blastocysts to predict and verify copy number variations (CNVs) in each cell. We determined the chromosome copy number of each embryo by analysing the proportion of abnormal cells in each blastocyst. We used the Bland-Altman concordance and the Kappa test to evaluate the concordance between TE and ICM in the both groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at a public tertiary hospital in China, where all the embryo operations, including oocytes retrieval, ST, and ICSI, were performed in the embryo laboratory. We utilized single-cell multi-omics sequencing technology at the Biomedical Pioneering Innovation Center, School of Life Sciences, Peking University, to analyse the blastocysts. Transcriptome sequencing was used to predict the CNV of each cell through bioinformatics analysis, and the results were validated using the DNA methylation library of each cell to confirm chromosomal normalcy. We conducted statistical analysis and graphical plotting using R 4.2.1, SPSS 27, and GraphPad Prism 9.3. MAIN RESULTS AND THE ROLE OF CHANCE: Mean age of the volunteers, the blastocyst morphology, and the developmental ratewere similar in ST and ICSI groups. The blastocysts in the ST group had some additional chromosomal types that were prone to variations beyond those enriched in the blastocysts of the ICSI group. Finally, both Bland-Altman concordance test and kappa concordancetest showed good chromosomal concordance between TE and ICM in the ICSI blastocysts (kappa = 0.659, P < 0.05), but not in ST blastocysts (P = 1.000), suggesting that the TE in reconstituted embryos is not representative of ICM. Gene functional annotation (GO and KEGG analyses) suggests that there may be new or additional pathways for CNV generation in ST embryos compared to ICSI embryos. LIMITATIONS, REASONS FOR CAUTION: This study was mainly limited by the small sample size and the limitations of single-cell multi-omics sequencing technology. To select eligible single cells, some cells of the embryos were eliminated or not labelled, resulting in a loss of information about them. The findings of this study are innovative and exploratory. A larger sample size of human embryos (especially ST embryos) and more accurate molecular genetics techniques for detecting CNV in single cells are needed to validate our results. WIDER IMPLICATIONS OF THE FINDINGS: Our study justifies the routine clinical use of PGT-A in ICSI blastocysts, as we found that the TE is a good substitute for ICM in predicting chromosomal abnormalities. While PGT-A is not entirely accurate, our data demonstrate good clinical feasibility. This trial was able to provide correct genetic counselling to patients regarding the reliability of PGT-A. Regarding ST blastocysts, the increased mosaicism rate and the inability of the TE to represent the chromosomal copy number of the ICM are both biological characteristics that differentiate them from ICSI blastocysts. Currently, ST is not used clinically on a large scale to produce blastocysts. However, if ST becomes more widely used in the future, our study will be the first to demonstrate that the use of PGT-A in ST blastocysts may not be as accurate as PGT-A for ICSI blastocysts. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key R&D Program of China (2018YFA0107601) and the National Key R&D Program of China (2018YFC1003003). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Cochlear Reimplantation Rate and Cause: a 22-Year, Single-Center Experience, and a Meta-Analysis and Systematic Review.

OBJECTIVES: In terms of cochlear reimplantation, there is no consensus on the definition, range, or calculation formulation for the reimplantation rate. This study aims to put forward a relatively standardized and more explicit definition based on a literature review, calculate the rate of cochlear reimplantation, and examine the classification and distribution of the reimplantation causes. DESIGN: A systematic review and retrospective study. A relatively clearer definition was used in this study: cochlear reimplantation is the implantation of new electrodes to reconstruct the auditory path, necessitated by the failure or abandonment of the initial implant. Seven English and Chinese databases were systematically searched for studies published before July 23, 2021 regarding patients who accepted cochlear reimplantation. Two researchers independently applied the inclusion and exclusion criteria to select studies and complete data extraction. As the effect size, the reimplantation rate was extracted and synthesized using a random-effects model, and subgroup and sensitivity analyses were performed to reduce heterogeneity. In addition, a retrospective study analyzed data on cochlear reimplantation in a tertiary hospital from April 1999 to August 2021. Kaplan-Meier survival analysis and the log-rank test were adopted to analyze the survival times of cochlear implants and compare them among different subgroups. RESULTS: A total of 144 articles were included, with 85,851 initial cochlear implantations and 4276 cochlear reimplantations. The pooled rate of cochlear reimplantation was 4.7% [95% CI (4.2% to 5.1%)] in 1989 to 2021, 6.8% [95% CI (4.5% to 9.2%)] before 2000, and 3.2% [95% CI (2.7% to 3.7%)] after 2000 ( P =0.003). Device failures accounted for the largest proportion of reimplantation (67.6% [95% CI (64.0% to 71.3%)], followed by medical reasons (28.9% [95% CI (25.7% to 32.0%)]). From April 1999 to August 2021, 1775 cochlear implants were performed in West China Hospital (1718 initial implantations and 57 reimplantations; reimplantation rate 3.3%). In total, 45 reimplantations (78.9%) were caused by device failure, 10 (17.5%) due to medical reasons, and 2 (3.5%) from unknown reasons. There was no difference in the survival time of implants between adults and children ( P = 0.558), while there existed a significant difference between patients receiving implants from different manufacturers ( P < 0.001). CONCLUSIONS: The cochlear reimplantation rate was relatively high, and more attention should be paid to formulating a standard definition, calculation formula, and effect assessment of cochlear reimplantation. It is necessary to establish a sound mechanism for long-term follow-up and rigorously conduct longitudinal cohort studies.

Global cognitive function is associated with sex, educational level, occupation type, and speech recognition rate in older Chinese adults: a single-center, prospective, cross-sectional study.

BACKGROUND: The development of cognitive impairment may be delayed if its risk factors are identified and detected, if its developmental trend can be predicted, and if early intervention can be performed. This study primarily aimed to investigate the association between global cognitive function and hearing loss, educational level, and occupation type and to determine any differences in such associations according to sex among older Chinese adults. METHODS: In this cross-sectional study, we prospectively recruited 219 individuals above 55 years old in an otolaryngology outpatient clinic who could write independently and had no severe vision impairment. Audiometric examinations included otoscopy, acoustic immittance, pure-tone audiometry, and speech audiometry for each ear. Cognitive function was evaluated by using the Chinese version of the Mini-Mental State Examination (MMSE). Multivariable linear regression analyses were performed to evaluate the relationship between variables and MMSE scores after adjusting for independent variables that were statistically significant in the univariable analyses. RESULTS: We enrolled 219 individuals: 98 men (mean ± standard deviation age, 63.08 ± 6.64 years) and 121 women (62.64 ± 7.17 years). The overall MMSE scores of the normal hearing group and the mild, moderate, and severe-to-profound hearing loss groups were 24.00 (5.00), 24.00 (5.00), 23.00 (5.00), and 23.00 (13.00), respectively. MMSE scores were higher among participants with higher educational levels (p < 0.001) and were significantly correlated with occupation type (p < 0.001). MMSE scores were significantly higher in men than in women (p < 0.001). However, after the analysis of the five subdomains, significant differences were only observed for attention and calculation (p < 0.001) and language (p = 0.011). We further compared the distribution of educational levels between men and women by using the chi-square test; there was no significant difference in educational level between the sexes (p = 0.070). CONCLUSIONS: We reported statistically significant relationships between global cognitive function and sex, educational level, and occupation type. Sex-specific strategies may be required to improve healthcare policies.

Overexpression of lncRNAs with endogenous lengths and functions using a lncRNA delivery system based on transposon.

BACKGROUND: Long noncoding RNAs (lncRNAs) play important roles in many physiological and pathological processes, this indicates that lncRNAs can serve as potential targets for gene therapy. Stable expression is a fundamental technology in the study of lncRNAs. The lentivirus is one of the most widely used delivery systems for stable expression. However, it was initially designed for mRNAs, and the applicability of lentiviral vectors for lncRNAs is largely unknown. RESULTS: We found that the lentiviral vector produces lncRNAs with improper termination, appending an extra fragment of ~ 2 kb to the 3'-end. Consequently, the secondary structures were changed, the RNA-protein interactions were blocked, and the functions were impaired in certain lncRNAs, which indicated that lentiviral vectors are not ideal delivery systems of lncRNAs. Here, we developed a novel lncRNA delivery method called the Expression of LncRNAs with Endogenous Characteristics using the Transposon System (ELECTS). By inserting a termination signal after the lncRNA sequence, ELECTS produces transcripts without 3'-flanking sequences and retains the native features and function of lncRNAs, which cannot be achieved by lentiviral vectors. Moreover, ELECTS presents no potential risk of infection for the operators and it takes much less time. ELECTS provides a reliable, convenient, safe, and efficient delivery method for stable expression of lncRNAs. CONCLUSIONS: Our study demonstrated that improper transcriptional termination from lentiviral vectors have fundamental effects on molecular action and cellular function of lncRNAs. The ELECTS system developed in this study will provide a convenient and reliable method for the lncRNA study.

Assessing determinants of health care prepayment in China: Economic growth or government willingness? New evidence from the continuous wavelet analysis.

Significant prepayment of health care is a crucial factor to ensure that all individuals have access to effective health services at affordable prices. The research questions we address here are as follows: What role does economic growth play in changing the level of health care prepayment? Does government's willingness to spend more on health mean higher prepayment rates in the health financing system? What are their dynamic relationships? These questions are addressed in China over the 1978 to 2014 period by employing the continuous wavelet analysis. We focus in particular on their correlations and lead-lag relationships across different frequency bands. Our findings clearly show that overall government willingness has a positive effect on health care prepayment level, while the impact of economic growth varies in the time-frequency domain. This variation could be demonstrated in 1980 to 1998, when the positive correlation between economic growth and health care prepayment level in the short term turned negative in the medium and long term, which indicated that China could not achieve mutual development of economic growth and social welfare within the market-oriented health system. Notably, the time-varying analysis indicates that China's new round of medical system reform since 2006 plays an important role in changing the correlations and lead-lag relationships. In particular, health care prepayment tended to lead government willingness during the 2006 to 2012 period since the increase of health subsidies and expenditures strengthened government responsibility over the health sector, and there existed a persistent mutual stimulation between economic growth and health care prepayment level across all frequency bands along with the reform.

On-Surface Synthesis of Adenine Oligomers via Ullmann Reaction.

Despite the fact that DNA bases have been well-studied on surface, the on-surface synthesis of one-dimensional DNA analogs through in situ reactions is still an interesting topic to be investigated. Herein, from the interplay of high-resolution scanning tunneling microscopy (STM) imaging and density functional theory (DFT) calculations, we have delicately designed a halogenated derivative of adenine as precursor to realize the combination of DNA bases and Ullmann reaction, and then successfully synthesized adenine oligomers on Au(111) via Ullmann coupling. This model system provides a possible bottom-up strategy of fabricating adenine oligomers on surface, which may further give access to man-made DNA strands with multiple bases.

The Museum as a platform for tobacco promotion in China.

The China Tobacco Museum in Shanghai is the largest in China, consisting of seven pavilions of tobacco-related exhibits. A focus group and previous survey data revealed that the museum conveys messages that make tobacco use appealing. Of the pavilions, three were found to contain blatant misinformation about tobacco and tobacco consumption. We argue that the China Tobacco Museum is a platform for tobacco promotion, a form of tobacco advertising, promotion and sponsorship, and thus contravenes the FCTC.

The gut-joint axis: Genetic evidence for a causal association between gut microbiota and seropositive rheumatoid arthritis and seronegative rheumatoid arthritis.

This study aimed to assess the causal relationship between GM and RA (seropositive RA and seronegative RA). A two-sample Mendelian randomization (MR) analysis was performed to assess the causality of GM on seropositive RA and seronegative RA. GM's genome-wide association study (GWAS) was used as the exposure, whereas the GWAS datasets of seropositive RA and seronegative RA were the outcomes. The primary analysis approach was used as inverse-variance weighted (IVW), followed by 3 additional MR methods (MR-Egger, weighted median, and weighted mode). Cochran's Q test was used to identify heterogeneity. The MR-Egger intercept test and leave-one-out analyses were used to assess horizontal pleiotropy. All statistical analyses were performed in R software. We discovered that Alloprevotella (IVW OR 0.84, 95% CI 0.71-0.99, P = .04) and Christensenellaceae R 7 group (IVW OR 0.71, 95% CI 0.52-0.99, P = .04) were negatively correlated with seropositive RA, Ruminococcaceae UCG002 (IVW OR 1.30, 95% CI 1.10-1.54, P = .002) was positively associated with seropositive RA. Actinomyces (IVW OR 0.73, 95% CI 0.54-0.99, P = .04), Christensenellaceae R 7 group (IVW OR 0.62, 95% CI 0.39-0.97, P = .04), Terrisporobacter (IVW OR 0.64, 95% CI 0.44-0.93, P = .02), Lactobacillales (IVW OR 0.65, 95% CI 0.47-0.90, P = .01) were negatively correlated with seronegative RA. The present MR analysis showed a protective effect of Alloprevotella and Christensenellaceae R 7 group and a potentially anti-protective effect of Ruminococcaceae UCG002 on seropositive RA; and a protective effect of Actinomyces, Christensenellaceae R 7 group, Terrisporobacter, and Lactobacillales on seronegative RA. Further experimental studies and randomized controlled trials are needed to validate these findings.

[Identification and expression profiling of SAPK gene family members in Dendrobium officinale].

To investigate the potential roles of stress-activated protein kinase (SAPK) gene family members in Dendrobium officinale, we employed multiple bioinformatics methods to identify the members of this family. The physicochemical properties, chromosomal localization, phylogenetic relationship, gene structure, and cis-acting elements of each D. officinale SAPK (DoSAPK) member were analyzed. In addition, their expression profiles in different tissues and under the low-temperature or salt stress treatment were determined by real-time fluorescence quantitative PCR. The results showed that D. officinale carried eight DoSAPK family members, which belonged to three groups (groups Ⅰ, Ⅱ, and Ⅲ). These genes were located on seven chromosomes, and there were two pairs of genes with replication. The DoSAPK members within the same group had similar gene structures, conserved motifs, and secondary structures. The cis-acting elements in the promoter regions of DoSAPK genes included abundant hormone and stress response elements. DoSAPK family members presented tissue-specific expression in D. officinale. Furthermore, they were differentially expressed under the low-temperature or salt stress treatment, which suggested that they might be involved in the responses to low-temperature and salt stress. Intriguingly, DoSAPK1 might play a role in the abiotic stress responses. The results laid a foundation for in-depth study of the members and roles of the DoSAPK gene family.

Association between primary Sjögren's syndrome and gut microbiota disruption: a systematic review and meta-analysis.

Evidence of gut microbiota disruption for numerous autoimmune diseases has accumulated. Recently, the relationship between the microbiota and primary Sjögren's disease has been increasingly investigated but has yet to be systematically elucidated. Therefore, a meta-analysis of publications dealing on topic was conducted. Case-control studies comparing primary Sjögren's syndrome patients and healthy controls (HCs) were systematically searched in nine databases from inception to March 1, 2023. The primary result quantitatively evaluated in this meta-analysis was the α-diversity. The secondary results qualitatively extracted and analyzed were the ß-diversity and relative abundance. In total, 22 case-control studies covering 915 pSS patients and 2103 HCs were examined. The quantitative analysis revealed a slight reduction in α-diversity in pSS patients compared to HCs, with a lower Shannon-Wiener index (SMD = - 0.46, (- 0.68, - 0.25), p < 0.0001, I2 = 71%), Chao1 richness estimator (SMD = - 0.59, (- 0.86, - 0.32), p < 0.0001, I2 = 81%), and ACE index (SMD = - 0.92, (- 1.64, - 0.19), p = 0.01, I2 = 86%). However, the Simpson index (SMD = 0.01, (- 0.43, 0.46) p = 0.95, I2 = 86%) was similar in the two groups. The ß-diversity significantly differed between pSS patients and HCs. Variations in the abundance of specific microbes and their metabolites and potential functions contribute to the pSS pathogenesis. Notably, the abundance of the phylum Firmicutes decreased, while that of Proteobacteria increased. SCFA-producing microbes including Ruminococcaceae, Lachnospiraceae, Faecalibacterium, Butyricicoccus, and Eubacterium hallii were depleted. In addition to diversity, the abundances of some specific microbes were related to clinical parameters. According to this systematic review and meta-analysis, gut microbiota dysbiosis, including reduced diversity, was associated with proinflammatory bacterium enrichment and anti-inflammatory bacterium depletion in pSS patients. Further research on the relationship between the gut microbiota and pSS is warranted.

Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection.

Tumor metastasis, responsible for approximately 90% of cancer-associated mortality, remains poorly understood. Here in this study, we employed a melanoma lung metastasis model to screen for metastasis-related genes. By sequential tail vein injection of mouse melanoma B16F10 cells and the subsequently derived cells from lung metastasis into BALB/c mice, we successfully obtained highly metastatic B16F15 cells after five rounds of in vivo screening. RNA-sequencing analysis of B16F15 and B16F10 cells revealed a number of differentially expressed genes, some of these genes have previously been associated with tumor metastasis while others are novel discoveries. The identification of these metastasis-related genes not only improves our understanding of the metastasis mechanisms, but also provides potential diagnostic biomarkers and therapeutic targets for metastatic melanoma.

[A preliminary study on wideband acoustic immittance of infants with normal bilateral middle ear function at the age of 1-5 months].

Objective:To explore preliminary characteristics of wideband acoustic immittance of 1- to 5-month-old infants who have bilateral normal middle ear function, so as to contribute to the clinical application of WAI test in the evaluation of middle ear function in infants. Methods:1- to 5-month-old infants were included. After the normal function of bilateral middle ear was determined by otoacoustic emission and high frequency acoustic immittance test, WAI test was performed and the relevant data were collected and analyzed. Results:There was no statistical difference in absorbance at the same frequency between the left ear and right ear of each group（P>0.05）. Absorbance of 4000 Hz increased at first and then decreased with the growth of physiological age, and the sound energy absorption rate of other frequencies decreased except 2670 Hz and 3364 Hz. Conclusion:The outcome of this study shows that it is necessary to establish the national normal value of WAI in 1- to 5-month-old infants who have bilateral normal middle ear function. The purpose of the development of middle ear system is to ensure that sounds in the speech frequency range can be transmitted and heard more effectively.

Comparison of wideband acoustic immittance in Chinese infants under three months of age with normal and abnormal middle ear function.

OBJECTIVES: This study aims to compare the characteristics of Wideband Acoustic Immittance (WAI) in Chinese infants under three months of age, with either normal or abnormal middle ear function. METHODS: We recruited 98 infants with either normal or abnormal middle ear function, and subsequently divided them into four groups based on their middle ear function and chronological age. The absorbances at tympanometric peak pressure (TPP) were collected across 1/3rd octave frequencies ranging from 226 to 8000 Hz. RESULTS: Among infants with normal middle ear function, no significant differences were observed concerning ear laterality. However, significant differences were noted at 3364 Hz and 4000 Hz with respect to age. For infants with either normal or abnormal middle ear function, we found significant differences at the majority of frequencies. Additionally, the receiver operating characteristic (ROC) curves and maxima Youden index indicated that absorbances at 1682 Hz and 1297 Hz could be employed to evaluate the middle ear function of infants at 1 and 2 months of age. CONCLUSION: This study demonstrates that WAI holds promise as a valuable tool for assessing the middle ear condition of infants at 1 and 2 months of age. Infants aged 1 and 2 years, having absorbance values equal to or greater than 0.7470 at 1682 Hz and 0.6775 at 1297 Hz respectively, may indicate normal middle ear function. Furthermore, it underscores the necessity of establishing ethnicity- and age-specific norms for WAI in infants under 3 months of age.

Allocation of emergency medical resources for epidemic diseases considering the heterogeneity of epidemic areas.

Background: The resources available to fight an epidemic are typically limited, and the time and effort required to control it grow as the start date of the containment effort are delayed. When the population is afflicted in various regions, scheduling a fair and acceptable distribution of limited available resources stored in multiple emergency resource centers to each epidemic area has become a serious problem that requires immediate resolution. Methods: This study presents an emergency medical logistics model for rapid response to public health emergencies. The proposed methodology consists of two recursive mechanisms: (1) time-varying forecasting of medical resources and (2) emergency medical resource allocation. Considering the epidemic's features and the heterogeneity of existing medical treatment capabilities in different epidemic areas, we provide the modified susceptible-exposed-infected-recovered (SEIR) model to predict the early stage emergency medical resource demand for epidemics. Then we define emergency indicators for each epidemic area based on this. By maximizing the weighted demand satisfaction rate and minimizing the total vehicle travel distance, we develop a bi-objective optimization model to determine the optimal medical resource allocation plan. Results: Decision-makers should assign appropriate values to parameters at various stages of the emergency process based on the actual situation, to ensure that the results obtained are feasible and effective. It is necessary to set up an appropriate number of supply points in the epidemic emergency medical logistics supply to effectively reduce rescue costs and improve the level of emergency services. Conclusions: Overall, this work provides managerial insights to improve decisions made on medical distribution as per demand forecasting for quick response to public health emergencies.