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*

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Aim To study the mechanism of action of licorice in alleviating cisplatin liver injury.Methods Forty-eight SD rats were randomly divided into a blank group,a model group,a positive control group and lico-rice administration groups(450,900 and 1 800 mg·kg-1).After 5 days of prophylactic administration,8 mg·kg-1 of cisplatin was injected intraperitoneally in-to the model,positive control,and licorice administra-tion groups to establish an acute liver injury model.LC-MS/MS untargeted metabolomics was used to ana-lyze the differential metabolites and metabolic pathways of licorice to alleviate cisplatin acute liver injury.Re-sults PLS-DA score plots showed significant separa-tion of metabolomics samples.The analysis yielded 119 differential metabolites associated with cisplatin liver injury,of which 31 differential metabolites were signifi-cantly regressed after licorice intervention and were mainly involved in D-arginine and D-ornithine metabo-lism;parathyroid hormone synthesis,secretion,and ac-tion;tyrosine metabolism;biosynthesis of phenylala-nine,tyrosine,and tryptophan;β-alanine metabolism;and amino acid and nucleotide sugar metabolism.Con-clusions Metabolomics analysis indicates that licorice can alter the metabolic profile of cisplatin-induced he-patic injury rats,and its mechanism of action may be related to its improvement of the levels of differential metabolites and its involvement in the regulation of a-mino acid metabolism and other related pathways.

Humans ; Child ; COVID-19/complications* ; Brain Diseases ; Myositis/complications* ; Kidney ; Liver Failure, Acute/complications* ; Acute Kidney Injury/complications*

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective To investigate the effect and mechanism of astrocytes on the proliferation of neural stem cells (NSCs) in adult and juvenile hippocampus microenvironment. Methods Hippocampal astrocytes were isolated and cultured from 5 female SD rats at day 1 and week 30 postnatal, respectively; Embryonic hippocampus NSCs was isolated and cultured from 1 SD rat at day 15 of gestation; Conditioned astrocyte culture medium(CM) was collected for NSCs culture; Flow cytometry and CCK-8 were used to detect the proliferation of NSCs cultured in CM. Colony stimulating factor 1 (CSF-1) with differential expression was screened by mass spectrometry after cultured astrocyte CM. Western blotting and ELISA were used to verify the result of mass spectrometry. Immunofluorescence, flow cytometry and CCK-8 were used to detect the proliferation of NSCs treated with different concentrations of CSF-1 recombinant protein (20 μg/ L, 100 μg/ L, 1 mg/ L and 5 mg/ L). Results Compared with the adult group, the CM of hippocampal astrocytes in the young group could promote the proliferation of NSCs(P<0. 01); Compared with the conditioned medium of hippocampal astrocytes in the juvenile group, the expression of CSF-1 in the hippocampus of the elder group was significantly up-regulated(P<0. 01); At 20 μg/ L, CSF-1 promoted the proliferation of NSCs(P<0. 01), and 5 mg/ L CSF-1 inhibited significantly the proliferation of NSCs(P<0. 01). Conclusion The secretion of CSF-1 by astrocytes in hippocampal microenvironment can regulate the proliferation of NSCs with the development of the times.

Myopia is currently one of the eye diseases that seriously threaten patients' vision worldwide, and its occurrence and development is a complex mechanism. It has been found that retinal pigment epithelium(RPE)cells play a key role in the progression of myopia. RPE cells mainly regulate cell function by regulating the expression of intracellular growth factor and matrix metalloproteinase-2(MMP-2)through the signal pathway of mammalian target of rapamycin(mTOR). At the same time, RPE cells can also be regulated by dopamine receptor agonists, so that cell function changes. When dopamine receptor activation weakened, RPE cell function will be impaired, thus promoting the development of myopia. Studies have shown that the expression of acetylcholine and all-trans retinoic acid in RPE cells can regulate the secretion of growth factors by RPE cells, and the growth factors act on scleral fibroblasts, thus indirectly regulating the course of myopia. Additionally, some studies have shown that RPE cells can coordinate the regulation of γ-aminobutyric acid on scleral cells and indirectly regulate the course of myopia. Besides, the expression of microRNA(microRNA)in RPE cells, such as microRNA-328 and microRNA-29a, was found through previous studies that they can affect the content and composition of extracellular matrix by regulating the expression of MMP-2 in RPE cells, thus leading to the occurrence and development of myopia. Therefore, the expression of multiple signaling pathways and miRNA in RPE cells are closely related to the occurrence and development of myopia. This article reviews the research progress of the molecular mechanism of RPE in the development of myopia, with a view to provide some theoretical basis for the specific molecular mechanism in the development of myopia.

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.
Mice ; Animals ; Antioxidants/analysis* ; Plant Extracts/pharmacology* ; Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Paeonia/chemistry* ; Glutathione/analysis*

Child ; Humans ; Toxoplasmosis, Cerebral ; Hematopoietic Stem Cell Transplantation ; Thalassemia