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*

Probiotics have shown excellent application prospects in preventing and treating many diseases. However, their sensitivity to the harsh environment in vivo always leads to a massive loss of viability and insufficient therapeutic effect. Fortunately, modified probiotics have emerged and provide multiple possibilities for their use in various diseases. Modification not only endows probiotics with extra capacity to resist severe environments but also gives them exogenous characteristics, such as prolonged retention time and improved therapeutic effects. Modified probiotics could combine with other therapies, which has opened up new avenues to enhance the efficacy of probiotic-based therapy. In this review, we have summarized the current physicochemical and biological modification strategies of probiotics. In addition, the progress of research on probiotic-based combination therapy has also been extensively reviewed, which contributes to the enhanced delivery of probiotics or other active constituents and provides new ideas for disease treatment, bioimaging, and diagnosis.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Objective:To observe the effects of sorafenib on the lesions and vascular growth factors in the mouse model of hepatic alveolar echinococcosis.Methods:One hundred healthy female Kunming mice weighing (20±4) g were used to establish a model of alveolar echinococcosis infection by intraperitoneal injection of alveolar echinococcosis protoscoleces. After 6 weeks of feeding, the rats were divided into 5 groups, 15 rats in each group, which were given warm saline, albendazole (100 mg/kg), and sorafenib at high-dose (100 mg/kg), middle-dose (50 mg/kg) and low-dose (30 mg/kg) by gavage for 6 weeks, respectively. Eyeball blood and hepatic alveolar echinococcosis tissue were collected from the mice after the last administration, and the body weight of the mice and the lesion weight were weighed. The concentrations and expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor receptor-2 (VEGFR-2) in serum and lesion tissues were detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting.Results:There was no statistically significant difference in the body weight of mice among the saline group, albendazole group and low-dose, medium-dose and high-dose sorafenib groups ( F=0.43, P=0.784). The ratios of lesion weight to body weight in the above groups were (0.057±0.009), (0.031±0.005), (0.033±0.005), (0.031±0.005), and (0.031±0.005), respectively. The saline group had a higher ratio than the other four groups, and the differences were statistically significant (all P<0.05). The relative expression levels of HIF-1α, VEGF-A, VEGFR-2, CD31 and CD34 detected by Western blotting in the saline group were all higher than those in the albendazole group and the high-dose, medium-dose and low-dose sorafenib groups, and the differences were statistically significant (all P<0.05). The relative expression levels of the above proteins in the medium-dose and high-dose sorafenib groups were lower than those in the albendazole group, and the relative expression levels of the above proteins in the high-dose sorafenib group were also lower than those in the medium-dose sorafenib group, and the differences were statistically significant (all P<0.05). The concentration levels of HIF-1α, VEGF-A and VEGFR-2 in serum of mice in each group detected by ELISA were consistent with those detected by Western blotting. Conclusion:Sorafenib inhibits the proliferation of alveolar echinococcosis in mice by suppressing the expression of angiogenic factors in alveolar echinococcosis lesions.

Objective:To understand the composition of infectious pathogens and the changes in the epidemic characteristics of inpatients with acute respiratory tract infections in Pudong New Area of Shanghai, from 2018 to 2023.Methods:Specimens of inpatients with acute respiratory infection cases were collected from 14 healthcare institutions in Pudong New Area, Shanghai, from 2018-2023 and tested for eight respiratory pathogens: influenza virus, adenovirus, rhinovirus, parainfluenza virus, respiratory syncytial virus, common coronavirus, metapneumovirus, and bocavirus. The groups were divided into three periods,2018-2019, 2020-2022 and 2023, and the chi-square or Kruskal-Wallis rank sum test was used to compare the group differences. The SPSS 22.0 software was used for statistical analysis.Results:Among the 3 023 inpatients with acute respiratory infection, the positive rate of any virus was 24.25% (733/3 023). The positive rates of any virus in 2018-2019, 2020-2022, and 2023 were 33.40% (336/1 006), 12.01% (116/966), and 26.74% (281/1 051), respectively, and the differences were statistically significant ( χ2=128.20, P<0.001). Among the age groups, in 2018-2019 and 2020-2022, the positive rate of any virus was the highest in the <5 years age group (46.20% and 14.64%), while in 2023, the 15-59 years age group had the highest positive rate (32.97%). The positive rate of any virus in winter was the highest in 2018-2019 (53.21%) and 2020-2022 (17.58%), and the highest in autumn was in 2023 (31.53%). The peak positive rate of respiratory syncytial virus was in winter of 2018-2019 and 2020-2022, as well as the summer of 2023.The positive rates of influenza virus in 2018-2019, 2020-2022 and 2023 were 9.84%, 1.55% and 9.71%, respectively. Conclusions:The pathogen epidemic characteristics of inpatients with acute respiratory infection in Pudong New Area from 2018 to 2023 have shown certain changes. It is necessary to strengthen monitoring. Targeted prevention and control strategies should be developed and implemented in a timely manner.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Helicobacter pylori(Hp)is a major pathogen that causes peptic ulcer,mucosa-associated tissue lymphoma and gastric cancer.Adhesion colonization is a prerequisite for the pathogenesis of Hp.After infec-tion,Hp first uses urease to neutralize gastric acid,and then it adapts to the environment through motility and chemotactic swimming of flagella.Finally,Hp adheres to gastric epithelial cells through outer membrane pro-teins.Some outer membrane proteins have the biological effect of transporting virulence factors,mediating in-flammation and assisting Hp to produce pathological changes on human body.This paper reviews the mecha-nism of main colonization factors of Hp.

Background and aims:Liver fibrosis is a prevalent pathological stage of various chronic liver diseases and has the potential to progress to liver cirrhosis and hepatocellular carcinoma.However,experimental models for in vivo research are limited.Unexpectedly,increased liver inflammation and fibrosis were previously observed in mice treated with aluminum adjuvant(commercial Imject Alum,a mixture of Al(OH)3 and Mg(OH)2).Our study aimed to reveal the pathogenesis and pathological features of Imject Alum-induced liver injury and evaluate its potential as an experimental model of fibrotic liver disease.Methods and materials:C57BL/6J mice were randomly divided into the following four groups:(ⅰ)control group,which received phosphate-buffered saline injections on days 1,12,26,40,and 54;(ⅱ)Imject Alum(Al(OH)3 160 mg/kg)D26 group,which was administered with Imject Alum(Al(OH)3 160 mg/kg)on days 1,12,and 26;(ⅲ)Imject Alum(Al(OH)3 80 mg/kg)D54;and(ⅳ)Imject Alum(Al(OH)3 160 mg/kg)D54 groups,which were treated with 80 mg/kg and 160 mg/kg of Imject Alum(Al(OH)3),respectively,on days 1,12,26,40,and 54.All reagents were delivered by intraperitoneal injection.Serum biochemical pa-rameters,liver pathology,and expression of genes related to inflammation and fibrogenesis were eval-uated.Transcriptome sequencing was performed.The genetic characteristics of the Imject Alum-induced liver lesions in the existing fibrosis model and patients with cirrhosis were determined.Results:Administration of Imject Alum(Al(OH)3 160 mg/kg)at certain points for 54 days led to extensive hepatic inflammation and fibrosis,accompanied by disturbed bile acid metabolism in mice.Moreover,Imject Alum aggravated liver inflammation and injury by activating the pyroptosis-related inflamma-some pathway.Transcriptome analysis revealed that Imject Alum-induced liver lesions had differentially expressed genes that were significantly enriched in pathways related to inflammation,fibrogenesis,and multiple metabolic processes.Moreover,Imject Alum-induced liver lesions exhibited gene signatures similar to those of existing fibrosis models and patients with cirrhosis.Conclusions:Aluminum adjuvant(Imject Alum;Al(OH)3 160 mg/kg)administration at certain points for 54 days resulted in notable liver injury,inflammation,and fibrosis.This model had similar gene expression characteristics with existing fibrosis models and liver samples from patients with cirrhosis.Overall,aluminum adjuvant(Imject Alum)-induced mouse model may be a novel approach for estab-lishing a liver fibrosis animal model.

Objective:To systematically evaluate the efficacy of ATP bioluminescence technology versus traditional microbiology detection method in assessing flexible endoscope cleaning and disinfection.Methods:Eight Chinese and English databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Database, VIP Chinese Medical Journal Database and China Biology Medicine disc, were searched from inception to October 1, 2023. Comparative studies on evaluating post-reprocessing endoscope quality using both methods were included. Positive sample numbers and positive rates were taken as the main effect indicators, and the fixed effect model was used to conduct a meta-analysis of the included literature.Results:A total of 14 Chinese and English articles were included, involving 4 569 samples (gastroscopes, colonoscopes, duodenoscopes and fiberbronchoscopes). The pooled analysis demonstrated low heterogeneity across studies ( I2=23%), with a combined odds ratio ( OR) of 1.57 (95% CI: 1.27-1.94). It indicated a statistically significant difference in positive detection rates between the two methods ( P<0.001). However, funnel plot analysis suggested potential publication bias. Conclusion:ATP bioluminescence correlates with microbiological methods for monitoring endoscope reprocessing. While ATP offers rapid assessment advantages, its consistently higher positive rates preclude replacement of conventional microbiological verification for terminal disinfection.