Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Adolescent ; Adult ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prospective Studies ; Young Adult

OBJECTIVE:To investigate the possibility of constructing anti-cancer drug in-situ hydrogel with self-assembling peptide RAD16-Ⅰ. METHODS:The rheological parameters as storage modulus(G′),loss modulus(G″)and phase angle(Δ)of 0.1%,0.2% and 0.5% RAD16-Ⅰ solution containing paclitaxel or not were determined by rheometer before and after mixing with isometric phosphate buffer solution (PBS);RAD16-Ⅰ solution containing paclitaxel or not were mixed with breast cancer MDA-MB-435S cells culture medium to obtain hydrogel,the status and effect of which on cell morphology were observed by in-verted microscope (compared with paclitaxel solution). RESULTS:In RAD16-Ⅰ solution containing paclitaxel or not,G′was close to or slightly higher than G″,and G′and G″had changed slightly as the concentration of peptide increased. Compared with not mixed with PBS,G′increased significantly in concentration-dependent manner after mixed with PBS,and G″also increased but was slighter than G′;Δ decreased significantly. In cell culture media,RAD16-Ⅰ solutions containing paclitaxel could form hy-drogel and maintain their gel form,cancer cells kept same morphology after treated with hydrogel and same concentration of pacli-taxel solution for same time. CONCLUSIONS:RAD16-Ⅰ solutions containing paclitaxel can form hydrogel under simulated physi-ological conditions,which can maintain their gel form and have anti-cancer effect of paclitaxel.

Objective To study the effect of hepatitis E virus Open Reading Frame 3 protein on the proliferation and cell cycle of Chang liver cells (CCL13).Methods The pDsRed-Monomer-N1-ORF3 recombinant plasmid was transfected into CCL13 cells via lipofectamine 2 000 reagent,then assayed cell proliferation by MTT assay;Flow cytometric was used to detect cell cycle after dying with PI;and the cell cycle proteins expression were detected by western-blotting.Results pDsRed-Monomer-N1-ORF3 recombinant plasmid was successfully transfected into CCL13 cells,Expression of ORF3 can inhibit the proliferation activity of CCL13 cells from the 3rd day (P ＜ 0.01),and prevent the cell cycle in G0/G1 phase;Western Blot showed expression of cell cycle proteins cyclin D1 and cyclin E1 were decreased in ORF3 group compared with the control group;However,the expression of cyclin A2 and cyclin B1 had no significantly difference in three groups.Conclusions HEV-ORF3 can inhibits the proliferation activity of CCL13 cells by inhibition expression of cell cycle proteins cyclin D1 and cyclin E1.

Aim To construct the cell model targeted on the damage by α-synuclein for screening anti-Parkinson’s Disease (PD)compounds.Methods The cDNA fragment of α-synucle-in gene was obtained by PCR methods and inserted into the re-combinant prokaryotic plasmid by molecular cloning technique. The recombinant plasmid was transformed into Escherichia coli, and subsequently induced to express α-synuclein protein.The recombinant α-synuclein was purified and identified by affinity chromatography,immunoblotting and mass spectrometry.The cells damage by α-synuclein was evaluated through cell viability measured by 3-(4,5-dimethyl-2-thiazolyl )-2,5-diphenyl-2-H-tetrazolium bromide.Results The obtained cDNA fragment ofα-synuclein in accordance with its theoretic molecular weight was cloned into pET30a plasmid and verified by sequencing.The re-combinant plasmid was transformed into bacteria E.Coli.BL21 (DE3)and induced to express α-synuclein by isopropyl β-D-1 -thiogalactopyranoside (IPTG).The expression condition was op-timized according to the culture temperature,the concentration of IPTG and the proliferation state of bacteria.The purified α-synu-clein was proved to be a 1 5.3 ku molecule weight protein,and could be immunoblotted with anti-α-synuclein antibody.The pu-rified α-synuclein could decrease the viability of PC1 2 cells and primary neurons significantly,and its effect was in a concentra-tion-dependent manner.Conclusion We have succeeded in constructing the cell model targeted on the damage by α-synucle-in.

BACKGROUNDHearing impairment has been reported to be common in patients with mitochondrial disorders, a group of diseases characterized by pleiomorphic clinical manifestations due to defects in oxidative phosphorylation of mitochondria. This study aimed to investigate the audiological characteristics in a large cohort of patients with mitochondrial disease.

METHODSComprehensive audiological evaluations, including pure tone audiometry, tympanometry, speech audiometry, otoacoustic emissions, electrocochleography and auditory brainstem evoked potentials, were performed in 73 Chinese patients with mitochondrial encephalomyopathy and with confirmed mitochondrial DNA (mtDNA) defects.

RESULTSAmong the patients, 71% had hearing impairment. However, the incidence rate and severity of hearing impairment were much less in the chronic progressive external ophthalmoplegia (CPEO) subtype than in the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), myoclonic epilepsy with ragged red fibers (MERRF) and Kearns-Sayre syndrome (KSS) subtypes. While most of our patients had a predominantly cochlea origin for the hearing deficit, five patients had an auditory neuropathy spectrum disorder and three patients had impairment of both cochlea and auditory cortex.

CONCLUSIONSVarious portions of the auditory system could be involved in patients with mitochondrial diseases, including cochlea, auditory nerve, auditory pathway and cortex. Hearing loss was more associated with multisystem involvement. Genotype, mutant load of mtDNA and other unknown factors could contribute to heterogeneity of hearing impairment in mitochondrial disease.

Adolescent ; Adult ; Aged ; Child ; Female ; Hearing Loss ; physiopathology ; Hearing Loss, Central ; physiopathology ; Humans ; Male ; Middle Aged ; Mitochondrial Encephalomyopathies ; physiopathology ; Young Adult

Aim To investigate the role of chemokine-like factor 1 ( CKLF1 ) in SH-SY5 Y cell migration and its molecular regulatory mechanism. Methods SH-SY5Y cells were stimulated with CKLF1 for 0. 5 h, 2 h, 8 h and 24 h, respectively. The migration distance and the percentage of migration cells were recorded by CELLocate analysis. The phosphorylation of focal ad-hesion kinase ( FAK) at Tyr-397 site was detected by Western blot analysis. By chemotaxis assays, we con-firmed the chemotaxis of CKLF1. Furthermore, FAK inhibitor PF-573228 and PLCγ inhibitor U73122 were used for the research of molecular regulatory mecha-nisms involved. Results CKLF1 promoted cell migra-tion and induced a strong increase in the phosphoryla-tion level of FAK-pY397 , which were significantly at-tenuated by the presence of U73122 ( a specific inhibi-tor for PLCγ) . In addition, the chemotaxis of CKLF1 was obviously blocked by the FAK inhibitor PF-573228 . Conclusion CKLF1 induces SH-SY5 Y cell migration via PLCγ/FAK signaling pathway.

Aim To study the screening of the nucleo-tide sequences might be affected by α-syn in vitro. Methods The nucleotide sequences were synthesized according to the feature of base composition, and then mixed with the α-syn-GFP. The CD was used to ana-lyse the changes of the peak. Result The peak of the CD changed greatly when the α-syn-GFP mixed with the GC-box like sequence. Conclusion The α-syn-GFP might affect the GC-box like sequence after trans-located into the nuclei. Then, it plays a role in physio-logical and pathological conditions by affecting the reg-ulation of gene expression.

Objective To report the clinical and genetic features in a family with Mohr-Tranebjaerg syndrome (MTS).Methods After collecting clinical data of the family,visual and auditory evoked potentials,pure tone audiometry,transient evoked otoacoustic emissions and distortion product otoacoustic emissions were carried out in proband (Ⅲ5).The translocase of inner mitochondrial membrane 8 homolog A (TIMM8A) gene was sequenced in proband,Ⅰ2,Ⅱ 4 and Ⅱ 6.Results Ⅲ5,a 15-year-old boy presented with deafness,slurred speech,difficulty in finger extension and dystonia gradually since 2 years old.Ⅲ1,Ⅲ 2 and Ⅲ 3 presented with deafness at the age of 2.Ⅰ 2,Ⅱ 2,Ⅱ 4 and Ⅱ 6 showed mild decreased visual acuity at the age of 12.Visual evoked potentials revealed prolonged P100 latency in both eyes.Pure tone audiometry revealed severe sensorineural hearing loss.The auditory evoked potentials showed no wave in the bilateral ears.Otoacoustic emissions were not elicited bilaterally.A novel c.133-2delA mutation in TIMM8A gene was identified in Ⅲ 5,Ⅰ2,Ⅱ 4 and Ⅱ 6.Conclusions We confirm the MTS caused by a novel c.133-2delA mutation in TIMM8A gene.Except for the deafness,the development of other symptoms of the disease vary obviously from case to case in the same family.The female carriers with mild lesion of optic nerves.