OBJECTIVE To evaluate the efficacy of oral and facial muscle functional training in treating adult obstructive sleep apnea(OSA)and to identify clinical indicators influencing treatment outcomes.METHODS Through a prospective cohort study,patients diagnosed with OSA in the study unit were recruited to undergo a 3-month myofunctional therapy,including soft palate-related muscles,tongue muscles,buccal muscles,and labial muscles in multiple muscle groups,once a day,five times a week,with the use of offline clinic guidance,and the APP program video follow up training for effective training.Data were collected on multiple dimensions including physical signs,sleep breathing monitoring parameters,and airway measurements from imaging studies.Treatment efficacy was assessed by comparing subjective and objective sleep indicators before and after training.Patients were categorized into effective and ineffective groups based on treatment outcomes.Differences in baseline clinical indicators between these groups were analyzed using univariate and multivariate regression analyses.RESULTS The study finally included 58 people,51 males and 7 females,age(38.36±8.96)years,BMI(27.14±3.68)kg/m2,AHI of the enrolled patients was reduced from(31.27±22.28)times/h pre-training to(26.27±21.38)times/h post-training,the minimum oxygen saturation was increased from(78.43±10.07)%to(80.50±10.06)%,snoring index decreased from(62.80±75.20)times/h to(36.40±43.19)times/h,and ESS score decreased from 7.00±5.31 pre-training to 5.50±3.17.By comparing the effective and ineffective groups,it was found that there was a statistically significant difference in the tongue position and ESS scores between the two groups(both P<0.05),while no significant differences were found in gender,age,neck circumference,posterior soft palate area,uvula area,posterior tongue area,or posterior epiglottic area(all P>0.05).Univariate logistic regression analysis indicated that tongue position,AHI,and ESS scores were factors affecting the efficacy of oral and facial muscle function training.Multivariate regression analysis revealed that AHI was an independent prognostic factor for this training in OSA patients.CONCLUSION Oral and facial muscle function training can improve both subjective and objective sleep breathing indices in OSA patients.Tongue position,AHI,and ESS scores may serve as prognostic factors for OSA treatment,aiding in guiding subsequent individualized intervention therapies.

OBJECTIVES: To develop an E-selectin-targeting nanomedicine delivery system that competitively inhibits E-selectin-neutrophil ligand binding to block neutrophil adhesion to vessels and suppress their recruitment to the lesion sites. METHODS: Doxorubicin hydrochloride (DOX)-loaded liposomes (IEL-Lip/DOX) conjugated with E-selectin-affinity peptide IELLQARC were developed using a post-insertion method. Two formulations [2-1P: Mol(PC): Mol(DPI)=100:1; 2-3P: 100:3] were prepared and their modification density and in vitro release characteristics were determined. Their targeting efficacy was assessed in a cell model of LPS-induced inflammation, a mouse model of acute lung injury (ALI), a rat femoral artery model of physical injury-induced inflammation, and a zebrafish model of local inflammation. RESULTS: The prepared IEL-Lip/DOX 2-1P and 2-3P had peptide modification densities of 4.76 and 7.57 pmoL/cm², respectively. Compared with unmodified liposomes, IEL-Lip/DOX exhibited significantly reduced 48-h cumulative release rates at pH 5.5. In the inflammation cell model, IEL-Lip/DOX showed increased uptake by activated inflammatory endothelial cells, and 2-1P exhibited a higher trans-endothelial ability. In ALI mice, the fluorescence intensity of IEL-Lip/Cy5.5 increased significantly in lung tissues by 53.71% [Z-(2-1P)] and 93.41% [Z-(2-3P)], and 2-1P had an increased distribution by 24.19% in the inflammatory lung tissue compared to normal mouse lung tissue. In rat femoral artery models, 2-1P had greater injured/normal vessel fluorescence intensity contrast. In the zebrafish models, both 2-1P and 2-3P showed increased aggregation at the site of inflammation. CONCLUSIONS This E-selectin-targeting nanomedicine delivery system efficiently targets activated inflammatory endothelial cells to increase drug concentration at the inflammatory site, which sheds light on new strategies for treating neutrophil-mediated inflammatory diseases and practicing the concept of "one drug for multiple diseases".
Animals ; Liposomes ; Rats ; Nanomedicine ; E-Selectin ; Drug Delivery Systems ; Inflammation/drug therapy* ; Mice ; Doxorubicin/analogs & derivatives* ; Zebrafish ; Acute Lung Injury/drug therapy*

Objective:To determine the prevalence of GJB2 gene c. 109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families. Methods:One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c. 109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c. 109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children′s Hospital of Ningbo University (Ethics No.: EC2023-009). Results:For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c. 109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c. 109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined ( n=53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined ( n=24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls ( P=0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1±12.0 dB nHL, P=0.005). Conclusion:Infants harboring the GJB2 c. 109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c. 109G>A variant can confer a more severe hearing loss.

Objective:To investigate the effects of influenza A virus(IAV)on macrophages based on expression of cytokines mediated by Janus kinase/signal transducer and activator of transcription(JAK/STAT)pathway,and to further explore the intervention effects of Ma Xing Shigan decoction drug containing serum.Methods:RAW264.7 was divided into control group,JAK/STAT signal pathway activator group,inhibitor group,model group,oseltamivir group,antiviral granule group and Ma Xing Shigan decoction group.Cell samples were collected after the intervention of IAV and subsequent treating of drug-containing serum for 24 and 48 hours.Secretion levels of IL-1β and CXCL2 in supernatant were detected by ELISA.mRNA expression levels of influenza virus Nuclear Pro-tein(NP),JAK1/2 and STAT1 of cells were detected by RT-qPCR.Protein expression levels of JAK1/2 and STAT1 were detected by Western blot,and protein expression levels of p-STAT1 was detected by immunofluorescence.Correlation between protein expression levels of p-STAT1 and secretion of IL-1β and CXCL2 were evaluated by Pearson correlation analysis.Results:Secretion levels of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2,STAT1,protein levels of JAK1/2,STAT1 and p-STAT1 were increased,and protein levels of p-STAT1 was positively correlated with the secretion of IL-1β and CXCL2.Ma Xing Shigan decoction could down-regulate secretions of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2 and STAT1,protein expression levels of JAK1,JAK2,STAT1 and p-STAT1.Conclusion:Activation of JAK1/2-STAT1 signal pathway and imbalance of inflammatory factors may be one of the molecular mechanisms of immunopathological damage of macrophages induced by IAV.Ma Xing Shigan decoction may alle-viate pathogenic effects of IAV by regulating this signal pathway.

OBJECTIVE: To determine the prevalence of GJB2 gene c.109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families. METHODS: One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c.109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c.109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children's Hospital of Ningbo University (Ethics No.: EC2023-009). RESULTS: For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c.109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c.109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined (n = 53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined (n = 24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls (P = 0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1 ± 12.0 dB nHL, P = 0.005). CONCLUSION Infants harboring the GJB2 c.109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c.109G>A variant can confer a more severe hearing loss.
Humans ; Connexin 26/genetics* ; Female ; Male ; Infant, Newborn ; Infant ; Hearing Loss/genetics* ; Retrospective Studies ; Child, Preschool ; Child ; Genotype ; Connexins/genetics* ; Mutation

Objective:To determine the prevalence of GJB2 gene c. 109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families. Methods:One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c. 109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c. 109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children′s Hospital of Ningbo University (Ethics No.: EC2023-009). Results:For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c. 109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c. 109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined ( n=53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined ( n=24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls ( P=0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1±12.0 dB nHL, P=0.005). Conclusion:Infants harboring the GJB2 c. 109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c. 109G>A variant can confer a more severe hearing loss.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective To explore the characteristics and molecular mechanisms of dynamic changes in ovarian function during natural aging in mice.Methods Eighteen female ICR mice of 2,6,10 and 14 months of age(referred to as 2 M,6 M,10 M,and 14 M)were included.The estrous cycle,ovarian index,pregnancy rate and embryo number were detected.The number of follicles was observed using HE staining.Serum anti-Müllerian hormone(AMH)levels were measured using ELISA.Protein and mRNA expression of P16,P21,proliferator-activated receptor-γ coactivator-1α(PGC-1α),and mitochondrial transcription factor A(TFAM)were detected through IHC and qPCR,respectively,and the protein expression of PGC-1α and TFAM was detected by Western blot.Relationships between indicators were evaluated based on Spearman's rank correlation coefficients and logistic regression analyses.Results Compared with estimates in the 2 M group,the percentage of estrous cycle disorders(P＜0.05 in 10 M group,P＜0.01 in 14 M group),ovarian index(P＜0.05 in 10 M group,P＜0.01 in 14 M group),serum AMH level(P＜0.01 in 10 M group,P＜0.01 in 14 M group),number of embryos(P＜0.01 in the 10 M group,P＜0.01 in 14 M group),and pregnancy rate(P＜0.01 in 14 M group)were significantly lower;the number of follicles at all levels and total number of follicles were lower(all P＜0.01),and the number of atretic follicles(all P＜0.01)was higher.Furthermore,P16 and P21 mRNA(P16:P＜0.01 in 10 M and 14 M groups;P21:P＜0.05 in 10 M group,P＜0.01 in 14 M group)and protein levels(P16:P＜0.01 in each group;P21:P＜0.01 in 10 M and 14 M groups)were elevated.Spearman's correlation analyses showed that the age in months was negatively correlated with the ovarian index,serum AMH level,primordial follicle number,number of embryos,and expression of PGC-1αand TFAM and positively correlated with the expression of atretic follicle,P16 and P21(all P＜0.01).Logistic regression analysis revealed a significant negative correlation between the age in months and pregnancy rate(P＜0.01).PGC-1α mRNA was significantly decreased(all P＜0.01),and TFAM mRNA was significantly decreased in 10 M and 14 M groups(P＜0.01).PGC-1α levels were significantly decreased in the 10 M group(IHC:P＜0.05;Western blot:P＜0.01)and 14 M group(all P＜0.01);TFAM levels were significantly lower in 6 M,10 M,and 14 M groups than in the 2 M group(IHC:P＜0.01;Western blot:P＜0.01).Compared with the 2 M group,expression levels of PGC-1α and TFAM were positively correlated with the ovarian index and serum AMH level and negatively correlated with P16 and P21 expression(all P＜0.01).Conclusions Ovarian function in mice declines progressively with age in months,as reflected by reductions in follicles and fertility and the up-regulation of aging markers,which may be associated with the decreased expression of the mitochondrial biogenesis factors PGC-1α and TFAM.

Objective To explore the characteristics and molecular mechanisms of dynamic changes in ovarian function during natural aging in mice.Methods Eighteen female ICR mice of 2,6,10 and 14 months of age(referred to as 2 M,6 M,10 M,and 14 M)were included.The estrous cycle,ovarian index,pregnancy rate and embryo number were detected.The number of follicles was observed using HE staining.Serum anti-Müllerian hormone(AMH)levels were measured using ELISA.Protein and mRNA expression of P16,P21,proliferator-activated receptor-γ coactivator-1α(PGC-1α),and mitochondrial transcription factor A(TFAM)were detected through IHC and qPCR,respectively,and the protein expression of PGC-1α and TFAM was detected by Western blot.Relationships between indicators were evaluated based on Spearman's rank correlation coefficients and logistic regression analyses.Results Compared with estimates in the 2 M group,the percentage of estrous cycle disorders(P＜0.05 in 10 M group,P＜0.01 in 14 M group),ovarian index(P＜0.05 in 10 M group,P＜0.01 in 14 M group),serum AMH level(P＜0.01 in 10 M group,P＜0.01 in 14 M group),number of embryos(P＜0.01 in the 10 M group,P＜0.01 in 14 M group),and pregnancy rate(P＜0.01 in 14 M group)were significantly lower;the number of follicles at all levels and total number of follicles were lower(all P＜0.01),and the number of atretic follicles(all P＜0.01)was higher.Furthermore,P16 and P21 mRNA(P16:P＜0.01 in 10 M and 14 M groups;P21:P＜0.05 in 10 M group,P＜0.01 in 14 M group)and protein levels(P16:P＜0.01 in each group;P21:P＜0.01 in 10 M and 14 M groups)were elevated.Spearman's correlation analyses showed that the age in months was negatively correlated with the ovarian index,serum AMH level,primordial follicle number,number of embryos,and expression of PGC-1αand TFAM and positively correlated with the expression of atretic follicle,P16 and P21(all P＜0.01).Logistic regression analysis revealed a significant negative correlation between the age in months and pregnancy rate(P＜0.01).PGC-1α mRNA was significantly decreased(all P＜0.01),and TFAM mRNA was significantly decreased in 10 M and 14 M groups(P＜0.01).PGC-1α levels were significantly decreased in the 10 M group(IHC:P＜0.05;Western blot:P＜0.01)and 14 M group(all P＜0.01);TFAM levels were significantly lower in 6 M,10 M,and 14 M groups than in the 2 M group(IHC:P＜0.01;Western blot:P＜0.01).Compared with the 2 M group,expression levels of PGC-1α and TFAM were positively correlated with the ovarian index and serum AMH level and negatively correlated with P16 and P21 expression(all P＜0.01).Conclusions Ovarian function in mice declines progressively with age in months,as reflected by reductions in follicles and fertility and the up-regulation of aging markers,which may be associated with the decreased expression of the mitochondrial biogenesis factors PGC-1α and TFAM.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.