Objective To investigate the intervention effect of cordycepin on DCM rats and its reg-ulative effect on of AKT/GSK3β signaling pathway.Methods A total of 80 male SD rats were randomly divided into model group,cordycepin group,AKT inhibitor group and cordycepin+AKT inhibitor group,with 20 rats in each group.After the establishment of DCM model,corre-sponding intervention was given to each group.Another 20 healthy rats served as control group.Cardiac function indicators(LVEF,LVFS,LVESD,LVEDD),levels of IL-6,IL-1β,TNF-α,SOD,GSH-Px and MAD,and expression of AKT/GSK3β signaling pathway related proteins were de-termined and compared among the groups blotting.Results The model group had significantly lower LVEF and LVFS,decreased myocardial SOD and GSH-Px contents,and declined p-AKT/AKT and p-GSK3β/GSK3β,but increased LVESD and LVEDD and myocardial IL-6,IL-1β,TNF-αand MAD expression levels when compared with the control group(P＜0.05).Cordycepin treat-ment obtained increased LVEF and LVFS and myocardial tissue SOD,GSH-Px,Bcl-2,p-AKT/AKT and p-GSK3β/GSK3β protein expressions,and decreased LVESD and LVEDD and myocar-dial expression of IL-6,IL-1β,TNF-α,MAD and Bax than the model group(P＜0.05),while AKT inhibitor reversed all the changes induced by modelling(P＜0.05).Combination of cordycepin+AKT inhibitor resulted in lower LVEF,LVFS and myocardial SOD,GSH-Px,Bcl-2,p-AKT/AKT,p-GSK3β/GSK3β protein levels,and increased LVESD,LVEDD and expressions of IL-6,IL-1β,TNF-α,MAD and Bax protein in myocardial tissue when compared with cordycepin group(P＜0.05).And the combination also resulted in increases in LVEF and LVFS[(61.29±5.61)％vs(39.28±4.12)％,(39.05±3.43)％vs(24.47±2.73)％,P＜0.05]and decreases in LVESD and LVEDD(4.36±0.48 mm vs 6.97±0.69 mm,6.07±0.61 mm vs 9.02±0.85mm,P＜0.05)when compared with AKT inhibitor group.Conclusion Cordycepin improves cardiac function,myocar-dial injury,inflammation and oxidative stress in DCM rats probably by activating AKT/GSK3βsignaling pathway,and inhibits the apoptosis of cardiomyocyte.

Objective To investigate the intervention effect of cordycepin on DCM rats and its reg-ulative effect on of AKT/GSK3β signaling pathway.Methods A total of 80 male SD rats were randomly divided into model group,cordycepin group,AKT inhibitor group and cordycepin+AKT inhibitor group,with 20 rats in each group.After the establishment of DCM model,corre-sponding intervention was given to each group.Another 20 healthy rats served as control group.Cardiac function indicators(LVEF,LVFS,LVESD,LVEDD),levels of IL-6,IL-1β,TNF-α,SOD,GSH-Px and MAD,and expression of AKT/GSK3β signaling pathway related proteins were de-termined and compared among the groups blotting.Results The model group had significantly lower LVEF and LVFS,decreased myocardial SOD and GSH-Px contents,and declined p-AKT/AKT and p-GSK3β/GSK3β,but increased LVESD and LVEDD and myocardial IL-6,IL-1β,TNF-αand MAD expression levels when compared with the control group(P＜0.05).Cordycepin treat-ment obtained increased LVEF and LVFS and myocardial tissue SOD,GSH-Px,Bcl-2,p-AKT/AKT and p-GSK3β/GSK3β protein expressions,and decreased LVESD and LVEDD and myocar-dial expression of IL-6,IL-1β,TNF-α,MAD and Bax than the model group(P＜0.05),while AKT inhibitor reversed all the changes induced by modelling(P＜0.05).Combination of cordycepin+AKT inhibitor resulted in lower LVEF,LVFS and myocardial SOD,GSH-Px,Bcl-2,p-AKT/AKT,p-GSK3β/GSK3β protein levels,and increased LVESD,LVEDD and expressions of IL-6,IL-1β,TNF-α,MAD and Bax protein in myocardial tissue when compared with cordycepin group(P＜0.05).And the combination also resulted in increases in LVEF and LVFS[(61.29±5.61)％vs(39.28±4.12)％,(39.05±3.43)％vs(24.47±2.73)％,P＜0.05]and decreases in LVESD and LVEDD(4.36±0.48 mm vs 6.97±0.69 mm,6.07±0.61 mm vs 9.02±0.85mm,P＜0.05)when compared with AKT inhibitor group.Conclusion Cordycepin improves cardiac function,myocar-dial injury,inflammation and oxidative stress in DCM rats probably by activating AKT/GSK3βsignaling pathway,and inhibits the apoptosis of cardiomyocyte.

Objective:To investigate the clinical features, molecular etiology, and treatment of a family with Treacher Collins Syndrome 2 (TCS2).Methods:Information of the proband (female, 8 years old) including medical history and family history was collected. Physical examination and examinations concerning laboratory, audiology, and radiology were performed on the proband. Physical examination was also performed on the family members. Genomic DNA of proband was extracted for whole exome sequencing, and then the genomic DNA of family members was extracted for Sanger sequencing. POLR1D and TCS2 related literatures published before August 31,2023 were searched and sifted in PubMed and CKNI databases. The clinical characteristics of TCS2 were summarized. Results:The proband had poor hearing since childhood, with pure tone audiometry indicating conductive hearing loss. She had a smaller jaw, bilateral preauricular fistulas and cup-shaped ear deformities. Temporal bone CT scan revealed deformities in the left external ear canal, bilateral middle ear and inner ear. A bone-conduction hearing aid device was surgically implanted, resulting in restoration of almost normal hearing levels. The proband′s mother also had a slightly smaller jaw. Genetic analysis revealed a novel heterozygous variant NM_015972.4:c.38_47del in the POLR1D gene in the proband, which was inherited from her mother. A review of the literature revealed no clear evidence of genotype-phenotype correlation in TCS2. Conclusions:Molecular diagnosis plays a vital role in the diagnosis of TCS2. Patients with normal facial phenotype may be carriers of pathogenic variants in the POLR1D gene and have the risk of passing it to the offsprings with complete penetrance. Proper bone conductive hearing devices can improve the quality of life of TCS2 patients.

OBJECTIVE: To explore the genetic basis for four Chinese pedigrees affected with Waardenburg syndrome (WS). METHODS: Four WS probands and their pedigree members who had presented at the First Affiliated Hospital of Zhengzhou University between July 2021 and March 2022 were selected as the study subjects. Proband 1, a 2-year-and-11-month female, had blurred speech for over 2 years. Proband 2, a 10-year-old female, had bilateral hearing loss for 8 years. Proband 3, a 28-year-old male, had right side hearing loss for over 10 years. Proband 4, a 2-year-old male, had left side hearing loss for one year. Clinical data of the four probands and their pedigree members were collected, and auxiliary examinations were carried out. Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: Proband 1, with profound bilateral sensorineural hearing loss, blue iris and dystopia canthorum, was found to have harbored a heterozygous c.667C>T (p.Arg223Ter) nonsense variant of the PAX3 gene, which was inherited from her father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PM2_Supporting+PP4), and the proband was diagnosed with WS type I. Proband 2, with moderate sensorineural hearing loss on the right side and severe sensorineural hearing loss on the left side, has harbored a heterozygous frameshifting c.1018_1022del (p.Val340SerfsTer60) variant of the SOX10 gene. Neither of her parents has harbored the same variant. Based on the ACMG guidelines, it was classified as pathogenic (PVS1+PM2_Supporting+PP4+PM6), and the proband was diagnosed with WS type II. Proband 3, with profound sensorineural hearing loss on the right side, has harbored a heterozygous c.23delC (p.Ser8TrpfsTer5) frameshifting variant of the SOX10 gene. Based on the ACMG guidelines, it was classified as pathogenic (PVS1+PM2_Supporting+PP4), and the proband was diagnosed with WS type II. Proband 4, with profound sensorineural hearing loss on the left side, has harbored a heterozygous c.7G>T (p.Glu3Ter) nonsense variant of the MITF gene which was inherited from his mother. Based on the ACMG guidelines, the variant was classified as pathogenic (PVS1+PM2_Supporting+PP4), and the proband was diagnosed with WS type II. CONCLUSION By genetic testing, the four probands were all diagnosed with WS. Above finding has facilitated molecular diagnosis and genetic counseling for their pedigrees.
Female ; Humans ; Male ; Deafness ; East Asian People ; Hearing Loss, Sensorineural/genetics* ; Mutation ; Pedigree ; Phenotype ; Waardenburg Syndrome/diagnosis*

Objective To evaluate the effect of intensive hypertension management model for patients with uncontrolled blood pressure in community.Methods Three hundred and seven hypertensive patients,whose blood pressure was not controlled with administration of two or more kinds of antihypertensive drugs,entered in the intensive management program from May 2015 to December 2017.Using calcium channel blockers,angiotensin converting enzyme inhibitors or angiotensin receptor blockers and diuretic as the primary scheme,the medication was adjusted by general practitioners under the guidance of specialists in tertiary hospitals.The "seamless" two-way referral between community and tertiary hospitals was implemented,and the blood pressure control,medication and adverse effects were analyzed.Results Among 307 patients,157 were males (51.1％) and the mean age was (65.0±8.6) years.There were 246 (80.0％)patients with moderate and severe hypertension 44 (14.3％) patients complicated with diabetes,and 63(20.5％) patients having comorbidities,and the patients with high risk or extremely high-risk accounted for 85.0％ (261/307).Through (3.97± 1.21) months (1-6 months) intensive management,systolic blood pressure decreased from (167.56±16.73)mmHg(1 mmHg=0.133 kPa) in the baseline to (132.79±11.24)mmHg (t=33.34,P＜0.01),and diastolic blood pressure from (95.34± 12.59) mmHg to(79.11 ±7.85) mmHg (t=23.67,P＜0.01),blood pressure control rate was 75.6％(232/307).No serious adverse reactions occurred.During the period 42 patients were referral to hospital through green channel with a referral rate of 13.7％,and six patients were diagnosed as secondary hypertension.Angiotensin receptor antagonists and calcium antagonists were the main antihypertensive drugs.After intensive management patients taking three or more antihypertensive drugs increased by 158 and those taking diuretics increased by 116.Conclusions The intensive management model is effective in patients with uncontrolled blood pressure in community.Early use of C+A,A+D,and A+C+D treatment schemes for uncontrolled patients in the community can improve the rate of reaching the target and is safe.

Objective: To discuss the possible reasons for cerebrospinal fluid (CSF) gusher in cochlear implantation (CI) with inner ear abnormality. Method: A retrospective analysis was performed on 340 cases who underwent CI from January 2013 to December 2016 in Division of Otology, Otorhinolaryngology Hospital, the First Affiliated Hospital of Zhengzhou University. Among them, 96 cases had inner ear abnormalities. Imaging examinations were performed on these patients, and classification of inner ear malformation was done according to the results. Results: Among the cases with inner ear abnormality, 9.4% (9/96) suffered from CSF gusher during CI. The inner ear abnormalities were found to be as follows: 3 cases had incomplete partition type Ⅰ; 1 case had incomplete partition type Ⅰ with semicircular canal dysplasia; 1 case had common cavity deformity; 1 case had enlarged vestibular aqueducts and common cavity deformity; 2 cases had Mondini deformity. All of these cases had bony defect in the fundus of the internal acoustic meatus observed on CT scans. Another case was type 1 cochlear aqueduct with round window aplasia. Conclusions Defects in the modiolus or fundus of the internal acoustic meatus is the main reason for CSF gusher during CI. A patent cochlear aqueduct is another possible reason.

Objective: To discuss the prediction of round window(RW) visibility in cochlear implantation(CI) with temporal bone high resolution computed tomography(HRCT). Methods: From January 2013 to January 2017, 130 cases underwent both HRCT and CI in our hospital were analyzed. The distance from facial nerve to posterior canal wall(FWD), the angle between facial nerve and inner margin of round window(FRA), and the angle between facial nerve and tympanic anulus to inner margin of round window(FRAA) were detected at the level of round window on axial temporal bone HRCT. A line parallel to the posterior wall of ear canal was drawn from the anterior wall of facial nerve at the level of round window on axial temporal bone HRCT and its relationship with round window was detected (facial-round window line, FRL): type0-posterior to the round window, type1-between the round window, type2-anterior to the round window. Their(FWD, FRA, FRAA, FRL) relationships with intra-operative round window visibility were analyzed by SPSS 17.0 software. Results: FWD(F=18.76, P=0.00), FRA(F=34.57, P=0.00), FRAA (F=14.24, P=0.00) could affect the intra-operative RW visibility significantly. RW could be exposed completely during CI when preoperative HRCT showing type0 FRL. RW might be partly exposed and not exposed when preoperative HRCT showing type1 and type2 FRL respectively. Conclusion FWD, FRA, FRAA and FRL of temporal bone HRCT can predict intra-operative round window visibility effectively in CI surgery.

Objective To discuss the clinical characteristic of middle ear malformation with cholesteatoma.Methods From September,2011 to November,2016,23 cases of middle ear malformation with cholesteatoma were collected.Their symptoms,ENT examination,temporal bone high resolution computed tomography (HRCT) and intraoperative findings were analyzed.Results All 23 patients had hearing loss.90.0％ patients had ear discharge and tinnitus.86.96％ patients had perforation in pars flaccida of tympanic membrane.95.7％ patients had poor mastoid gasification.73.9％ patients had undeveloped or dysplastic tympanic antrum.100％ patients had destruction of the ossicular chain.56.5％ patients had malformation of the ossicular chain.52.2％ patients had exposed facial nerve.30.4％ patients had hyperplasia of the attic bone.Conclusion The symptoms and physical examinations of middle ear malformation with cholesteatoma are the same as middle ear cholesteatoma.Poor mastoid gasification can usually be detected on temporal bone HRCT.The most common malformation is dysplastic tympanic antrum,followed by malformation of the ossicular chain,exposed facial nerve and hyperplasia of the attic bone.Temporal bone HRCT can indicate the malformation and destruction quite well.

BACKGROUND: Currently, the morphologic characteristics of the torn discoid lateral meniscus remain unclear, andmorphological indexes used to evaluate the discoid lateral meniscus tears still need to be explored. OBJECTIVE: To discuss the specificity and sensitivity of discoid lateral meniscal tears in children using morphological indexes. METHODS: Seventy-three patients (seventy-six knees) with torn discoid lateral meniscus underwentarthroscopy and MRI data of knee examinations were retrospectively reviewed. All MR images were double-blinded, independently, retrospectively analyzed by attending radiologist (doctor A) and sports physician (doctor B). The following morphological signs of discoid lateral meniscus, such as a internal displaced free edge sign, a hypertrophic free edge sign and a hypertrophied-horn sign, were selected to evaluate the discoid lateral meniscus tears. The likelihood of the discoid lateral meniscus tears was analyzed on basis of arthroscopic findings constituted the gold standard. Sensitivity, specificity and accuracy of MRI diagnosis of the discoid lateral meniscus tears by two physicians were calculated, and the consistency of diagnosis results by two physicians was evaluated using the Kappa statistics.RESULTS AND CONCLUSION: (1) The sensitivity, specificity and accuracy in the diagnosis of discoid lateral meniscustears by internal displaced free edge sign for doctor A were 19%, 94% and 53%, respectively, and for doctor B were 21%, 97% and 55%. (2) The sensitivity, specificity and accuracy in the diagnosis of discoid lateral meniscus tears by hypertrophic free edge sign for doctor A were 52%, 100% and 74%, respectively, and for doctor B were 57%, 97% and 75%. (3) The sensitivity, specificity and accuracy in the diagnosis of discoid lateral meniscus tears by hypertrophied-horn sign for doctor A were 26%, 97% and 58%, respectively, and for doctor B were 24%, 100% and 58%. (4) The sensitivity, specificity and accuracy in the diagnosis of discoid lateral meniscus tears by binding morphological index for doctor A were 86%, 91% and 87%, respectively, and for doctor B were 88%, 94% and 91%. (5) The Kappa statistics for discoid lateral meniscus tears respectively demonstrated a good inter-observer agreement (K > 0.75, P < 0.001). (6) These findings suggest that single morphological index used to evaluate the discoid lateral meniscus tears shows a good specificity, but which also shows a low sensitivity, while a binding morphological index can significantly improve the diagnostic sensitivity. Morphological characteristics may be reliable indexes to evaluate the discoid lateral meniscal tears in children.

Objective To investigate the development of auditory and speech skills and the safety and stability among the prelingually deaf children with Nurotron Venus cochlear implants.Methods A total of 78 cochlear implant subjects were recruited from the first of affiliated hospital of Zhengzhou university.They were divided into 5 groups according to the ages at the time of implantation: group A(between 13 and 24 months), group B(between 25 and 36 months),group C(between 37 and 48 months),group D(between 49 and 72 months),group E(between 73 and 96 months).Children were evaluated by IT-MAIS(group A and B) and MAIS(group C,D and E) before the surgery and 1 month,3 months,6 months, and 12 months after surgery.All children were evaluated by MUSS questionnaires 1 months, 3 months,6 months,and 12 months after surgery.Post-operative cochlear radiographs determine the position of the CIs.The complications and usage of The CIs were followed up.Results The auditory and speech ability of children with CIs improved constantly.The auditory and speech of different groups were statistically significant.All the surgeries of 78 cases Nurotron-Venus cochlear implants were successful.Post-operative cochlear radiographs showed electrodes in the normal position.2 cases had processor failures.The remaining CIs were implanted completely.Conclusion Within 1 year, the ability of auditory and speech improved gradually.The scores of auditory and speech about the small age groups are lower than older children in the early days.There is no influence on the audition in 12 months.Small children's scores of speech are lower than older children in 12 months.The better ability to integrate auditory information is , the better the ability to speak is.The Nurotron CIs work safety and effectively.