This study was aimed at exploring the interaction between the nucleoprotein(NP)of influenza A virus(IAV)and TRIM25.The physicochemical properties and protein structure of IAV NP protein were analyzed through bioinformatics methods.The interaction between IAV NP and TRIM25 proteins was simulated with molecular docking techniques,and the in-teraction sites were predicted.With the cDNA of the A/Puerto Rico/8/1934(H1N1)PR8 strain as the template,the NP pro-tein was cloned into the eukaryotic expression vector pCMV-C-Flag through PCR amplification,the eukaryotic expression re-combinant plasmid pCMV-Flag-NP was constructed,and the expression was further verified.The protein expression levels of pCMV-Flag-NP and pCMV-HA-TRIM25 were detected at various time periods.The interaction between NP protein and TRIM25 protein was verified by co-immunoprecipitation.The co-localization of NP protein and TRIM25 protein in cells was ob-served with laser confocal microscopy.Bioinformatics analysis revealed that the NP protein consists of 498 amino acids and 20 amino acids,and is an unstable hydrophilic protein.The NP protein has multiple phosphorylation sites,as well as N-glycosyla-tion and O-glycosylation sites,but no transmembrane domain or signal peptide domain.Additionally,the NP protein's second-ary structure consists of a high proportion of alpha-helices and random coils.The molecular docking prediction results indicated that IAV NP interacts with TRIM25 protein and has multiple potential interaction sites,including the 233rd alanine,234th ala-nine,236th lysine,and 440th alanine of the NP protein.After successfully constructing and expressing the IAV NP protein,we verified the interaction between IAV NP and TRIM25 protein by immunoprecipitation and laser confocal microscopy obser-vations.Our results together suggested that the structure of the IAV NP protein is closely related to its function,and its im-portance to the virus is clear.In addition,the interaction between IAV NP and TRIM25 protein may be associated with TRIM25's anti-influenza virus mechanism.Further in-depth research may provide new ideas for anti-influenza virus strategies.

This study was aimed at exploring the interaction between the nucleoprotein(NP)of influenza A virus(IAV)and TRIM25.The physicochemical properties and protein structure of IAV NP protein were analyzed through bioinformatics methods.The interaction between IAV NP and TRIM25 proteins was simulated with molecular docking techniques,and the in-teraction sites were predicted.With the cDNA of the A/Puerto Rico/8/1934(H1N1)PR8 strain as the template,the NP pro-tein was cloned into the eukaryotic expression vector pCMV-C-Flag through PCR amplification,the eukaryotic expression re-combinant plasmid pCMV-Flag-NP was constructed,and the expression was further verified.The protein expression levels of pCMV-Flag-NP and pCMV-HA-TRIM25 were detected at various time periods.The interaction between NP protein and TRIM25 protein was verified by co-immunoprecipitation.The co-localization of NP protein and TRIM25 protein in cells was ob-served with laser confocal microscopy.Bioinformatics analysis revealed that the NP protein consists of 498 amino acids and 20 amino acids,and is an unstable hydrophilic protein.The NP protein has multiple phosphorylation sites,as well as N-glycosyla-tion and O-glycosylation sites,but no transmembrane domain or signal peptide domain.Additionally,the NP protein's second-ary structure consists of a high proportion of alpha-helices and random coils.The molecular docking prediction results indicated that IAV NP interacts with TRIM25 protein and has multiple potential interaction sites,including the 233rd alanine,234th ala-nine,236th lysine,and 440th alanine of the NP protein.After successfully constructing and expressing the IAV NP protein,we verified the interaction between IAV NP and TRIM25 protein by immunoprecipitation and laser confocal microscopy obser-vations.Our results together suggested that the structure of the IAV NP protein is closely related to its function,and its im-portance to the virus is clear.In addition,the interaction between IAV NP and TRIM25 protein may be associated with TRIM25's anti-influenza virus mechanism.Further in-depth research may provide new ideas for anti-influenza virus strategies.

Objective To understand the pathogen detection of hospitalized patients before antimicrobial therapy in a hospital through implementation of comprehensive intervention measures,and provide reference basis for the de-velopment of targeted measures.Methods Hospitalized patients who received therapeutic antimicrobial agents in this hospital were selected as the research subjects.Patients who were hospitalized from January to May 2022 were selected as the pre-intervention group,comprehensive intervention measures were taken from June to October 2022,and those who were hospitalized from November 2022 to March 2023 were selected as the post-intervention group.The pathogen detection rate before antimicrobial therapy,sterile specimen detection rate,antimicrobial use rate,de-tection rate of key multidrug-resistant organisms of patients before and after the intervention were analyzed.Results Compared to before intervention,the proportion of pathogen detection rate before antimicrobial therapy(62.09％vs 74.04％),detection rate of healthcare-associated infection diagnosis-related pathogens(62.82％vs 92.73％),and sterile specimen detection rate(35.17％vs 41.06％)of hospitalized patients after intervention all increased signifi-cantly,with statistically significant differences(all P＜0.05).After intervention,pathogen detection rate before the combination use of key antimicrobial agents was not statistically different from before intervention(93.33％vs 90.48％,P＞0.05),while antimicrobial use rate was lower than before intervention(39.93％vs 44.95％,P＜0.05).There was no statistically significant difference in the detection rate of key multidrug-resistant organisms be-fore and after intervention(all P＞0.05).Conclusion Adopting scientific and rational intervention measures can improve the pathogen detection rate,provide a reference basis for the rational use of antimicrobial agents.There was no significant improvement in the pathogen detection rate before the combination use of key antimicrobial agents and the detection rate of key multidrug-resistant organisms,indicating that relevant measures still need to be further optimized.

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy

BACKGROUNDBilateral sudden sensorineural hearing loss (BSSHL) is rare and assumed to be a different clinical entity compared to unilateral SSHL (USSHL). This study examined the differences between the idiopathic BSSHL and USSHL.

METHODSForty-six sequential BSSHL patients (Se-BSSHL) and 68 simultaneous BSSHL (Si-BSSHL) were consecutively admitted between June 2008 and December 2015. Two sets of patients served as control groups: (1) USSHL patients with healthy contralateral ear and (2) USSHL patients with contralateral preexisting hearing loss (USSHLwCHL). We retrospectively analyzed differences among four cohorts using analysis of variance, Kruskal-Wallis test, Welch's t-test, and Chi-square test as appropriate before and after propensity score matching (PSM) based on age, gender, and body mass index (BMI).

RESULTSThe prevalence of idiopathic BSSHL was 8.6% (114/1329) among the total SSHL patients. In the total cohort, USSHL patients tended to be younger, female, and tended to have lower BMI, renal parameters, and total cholesterol in addition to higher high-density lipoprotein compared to the other three groups. Most routine blood indicators, some coagulation markers, and immunoglobulin M (H = 13.4, P = 0.004) were significantly different among the study groups. After PSM, the major significant differences were found in audiometric characteristics. Si-BSSHL and Se-BSSHL patients demonstrated similar hearing thresholds as USSHL but were significantly better than the USSHLwCHL patients across most frequencies before and after treatment (H = 30.0, P < 0.001 for initial hearing and H = 12.0, P = 0.007 for final hearing). Moreover, the BSSHL patients showed different hearing loss distribution patterns (more descending type, χ2 = 33.8, P = 0.001) with less hearing gain (H = 17.5, P < 0.001) compared to the USSHL patients.

CONCLUSIONSIdiopathic BSSHL is a relatively rare subtype of SSHL with a higher rate of descending audiogram type and inferior hearing outcome rather than being classified as a completely different disease entity compared to USSHL.

BACKGROUNDThe molecular genetic research showed the association between X-linked hearing loss and mutations in POU3F4. This research aimed to identify a POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family.

METHODSA series of clinical evaluations including medical history, otologic examinations, family history, audiologic testing, and a high-resolution computed tomography scan were performed for each patient. Bidirectional sequencing was carried out for all polymerase chain reaction products of the samples. Moreover, 834 controls with normal hearing were also tested.

RESULTSThe pedigree showed X-linkage recessive inheritance pattern, and pathogenic mutation (c.499C>T) was identified in the proband and his family member, which led to a premature termination prior to the entire POU domains. This mutation co-segregated with hearing loss in this family. No mutation of POU3F4 gene was found in 834 controls.

CONCLUSIONSA nonsense mutation is identified in a family displaying the pedigree consistent with X-linked recessive pattern in POU3F4 gene. In addition, we may provide molecular diagnosis and genetic counseling for this family.

Asian Continental Ancestry Group ; Child ; Deafness ; genetics ; Female ; Genetic Predisposition to Disease ; Hearing Loss ; genetics ; Humans ; Male ; Mutation ; genetics ; POU Domain Factors ; genetics ; Pedigree

BACKGROUNDHypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by haploinsufficiency of GATA binding protein 3 (GATA3) gene mutations, and hearing loss is the most frequent phenotypic feature. This study aimed at identifying the causative gene mutation for a three-generation Chinese family with HDR syndrome and analyzing auditory phenotypes in all familial HDR syndrome cases.

METHODSThree affected family members underwent otologic examinations, biochemistry tests, and other clinical evaluations. Targeted genes capture combining next-generation sequencing was performed within the family. Sanger sequencing was used to confirm the causative mutation. The auditory phenotypes of all reported familial HDR syndrome cases analyzed were provided.

RESULTSIn Chinese family 7121, a heterozygous nonsense mutation c.826C>T (p.R276*) was identified in GATA3. All the three affected members suffered from sensorineural deafness and hypocalcemia; however, renal dysplasia only appeared in the youngest patient. Furthermore, an overview of thirty HDR syndrome families with corresponding GATA3 mutations revealed that hearing impairment occurred earlier in the younger generation in at least nine familial cases (30%) and two thirds of them were found to carry premature stop mutations.

CONCLUSIONSThis study highlights the phenotypic heterogeneity of HDR and points to a possible genetic anticipation in patients with HDR, which needs to be further investigated.

Child ; Female ; GATA3 Transcription Factor ; genetics ; Genotype ; Hearing Loss ; genetics ; Hearing Loss, Sensorineural ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Hypoparathyroidism ; genetics ; Male ; Mutation ; genetics ; Nephrosis ; genetics ; Pedigree

BACKGROUNDThe prevalence of sudden sensorineural hearing loss in children (CSSNHL) is consistently increasing. However, the pathology and prognosis of CSSNHL are still poorly understood. This retrospective study evaluated clinical characteristics and possible associated factors of CSSNHL.

METHODSOne hundred and thirty-six CSSNHL patients treated in Department of Otolaryngology-Head and Neck Surgery and Institute of Otolaryngology at Chinese PLA General Hospital between July 2008 and August 2015 were included in this study. These patients were analyzed for clinical characteristics, audiological characteristics, laboratory examinations, and prognostic factors.

RESULTSAmong the 136 patients (151 ears), 121 patients (121 ears, 80.1%) were diagnosed with unilaterally CSSNHL, and 15 patients (30 ears, 19.9%) with bilateral CSSNHL. The complete recovery rate of CSSNHL was 9.3%, and the overall recovery rate was 37.7%. We found that initial degree of hearing loss, onset of treatment, tinnitus, the ascending type audiogram, gender, side of hearing loss, the recorded auditory brainstem response (ABR), and distortion product otoacoustic emissions (DPOAEs) had prognostic significance. Age, ear fullness, and vertigo had no significant correlation with recovery. Furthermore, the relevant blood tests showed 30.8% of the children had abnormal white blood cell (WBC) counts, 22.1% had elevated homocysteine levels, 65.8% had high alkaline phosphatase (ALP), 33.8% had high IgE antibody levels, and 86.1% had positive cytomegalovirus (CMV) IgG antibodies.

CONCLUSIONSCSSNHL commonly occurs unilaterally and results in severe hearing loss. Initial severe hearing loss and bilateral hearing loss are negative prognostic factors for hearing recovery, while positive prognostic factors include tinnitus, gender, the ascending type audiogram, early treatment, identifiable ABR waves, and DPOAEs. Age, vertigo, and ear fullness are not correlated with the recovery. Some serologic indicators, including the level of WBC, platelet, homocysteine, ALP, positive CMV IgG antibody, fibrinogen, and some immunologic indicators, are closely related to CSSNHL.

Adolescent ; Child ; Child, Preschool ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Loss, Sensorineural ; blood ; etiology ; physiopathology ; Humans ; Male ; Otoacoustic Emissions, Spontaneous ; Retrospective Studies

OBJECTIVETo investigate the effect of premature rupture of the membrane (PROM) on neonatal complications in premature infants.

METHODSThe registration information of 7684 preterm infants with gestational age <37 weeks were collected from the cooperative units in the task group between January 1, 2014 to December 31, 2014. Specially trained personnel from each cooperative units filled in the unified form in a standardized format to record the gender, gestational age, birth weight, PROM, placental abruption, antenatal corticosteroid, Apgar score, amniotic fluid pollution, and complications of the infants. The data were analyzed comparatively between the cases with PROM and those without (control).

RESULTSThe preterm mortality rate was significantly lower but the incidences of ICH, NEC, ROP and BPD were significantly higher in PROM group than in the control group (P<0.05). The 95% confidence interval of the OR value was <1 for mortality, and was >1 for ICH, NEC, ROP and BPD. After adjustment for gestational age, birth weight, gender, mode of delivery, placental abruption, placenta previa, prenatal hormones, gestational diabetes mellitus (GDM), gestational period hypertension and 5-min Apgar score <7, the incidences of NEC, ROP and BPD were significantly different between the two groups (P<0.05) with 95% confidence interval of OR value >1, but the mortality rate and incidence of ICH were not significantly different between the two groups (P>0.05).

CONCLUSIONPROM is a risk factor for NEC, ROP and BPD in preterm infants, and adequate intervention of PROM can reduce the incidences of such complications as NEC, ROP and BPD in the infants.

Apgar Score ; Birth Weight ; Female ; Fetal Membranes, Premature Rupture ; pathology ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Infant, Newborn, Diseases ; etiology ; Infant, Premature ; Pregnancy ; Risk Factors

BACKGROUNDThere are more than 300 genetic loci that have been found to be related to hereditary hearing impairment (HHI), including 92 causative genes for nonsyndromic hearing loss, among which 34 genes are related to autosomal dominant nonsyndromic HHI (ADNSHHI). Traditional linkage analysis and candidate gene sequencing are not effective at detecting the ADNSHHI, especially for the unconditional families that may have more than one pathogenic cause. This study identified two disease-causing genes TJP2 and GJB2 in a Chinese family with unconditional ADNSHHI.

METHODSTo decipher the genetic code of a Chinese family (family 686) with ADNSHHI, different gene screening techniques have been performed, including linkage analysis, candidate genes screening, high-throughput sequencing and Sanger sequencing. These techniques were done on samples obtained from this family over a period of 10 years.

RESULTSWe identified a pathogenic missense mutation, c. 2081G>A (p.G694E), in TJP2, a gene that plays a crucial role in apoptosis and age-related hearing loss (ARHL). The mutation was co-segregated in this pedigree in all, but not in the two patients who presented with different phenotypes from the other affected family members. In one of the two patients, we confirmed that the compound heterozygosity for p.Y136* and p.G45E in the GJB2 gene may account for the phenotype shown in this patient.

CONCLUSIONSWe identified the co-occurrence of two genetic causes in family 686. The possible disease-causing missense mutation of TJP2 in family 686 presents an opportunity for further investigation into ARHL. It is necessary to combine various genes screening methods, especially for some unconventional cases.

Adult ; Aged ; Asian Continental Ancestry Group ; Connexins ; genetics ; Exome ; genetics ; Female ; Genetic Linkage ; genetics ; Haplotypes ; genetics ; Hearing Loss, Sensorineural ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; genetics ; Pedigree ; Young Adult ; Zonula Occludens-2 Protein ; genetics