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.

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.

Objective To explore the feasibility,safety and effectiveness of ultrasound-guided biopsy of pancreatic lesions with exophytic and backward growth morphology.Methods Fifty-three patients with pancreatic lesions with exophytic and backward growth morphology who underwent ultrasound-guided biopsy were retrospectively collected.Conventional ultrasonic manifestations of lesions were observed,and the technical success rate,complication rate,repeat puncture rate,as well as the sensitivity,specificity and accuracy of biopsy were recorded.Results Totally 61 lesions were detected,with the maximum diameter of 1.4-7.3 cm and the median maximum diameter of 2.7 cm,located in pancreatic uncinate process(26/61,42.62％),head(12/61,19.67％),neck(13/61,21.31％)and body(10/61,42.62％),respectively,mainly presented as hypoechogenic(61/61,100％)and borderless(60/61,98.36％)masses tending to invade blood vessels(51/61,83.61％)and pancreatic ducts(40/61,65.57％).The technical success rate,complication rate and repeat puncture rate of ultrasound-guided biopsy was 100％(61/61),1.89％(1/53)and 21.31％(13/61),respectively,and the sensitivity,specificity and accuracy of biopsy diagnosis was 75.00％(45/60),100％(1/1)and 75.41％(46/61),respectively.Conclusion Ultrasound-guided biopsy was safe and feasible for pancreatic lesions with exophytic and backward growth morphology,but its diagnostic efficacy should be improved.

Objective:To investigate clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) complicated with asthma.Methods:A self-controlled study before and after treatment was conducted to retrospectively analyze 45 patients with moderate to severe atopic dermatitis combined with asthma who received dupilumab in the respiratory allergy clinic of North Theater Command General Hospital from January 2021 to May 2024, which age ≥12 years, including 27 males, 18 females. The treatment period was 4 to 12 months. All patients were treated with dupilumab combined with inhaled glucocorticoids and long-acting beta2-receptor agonists, as well as symptomatic drugs for atopic dermatitis. Analyze the clinical data of the patients before and after treatment, including lung function, asthma and AD-related assessment scales. Generalized estimation equation was used to analyze the simple effect of time on the repeated measurement data following non-normal distribution, and Wilcoxon signed rank test was used to compare the differences of each observation index before and after treatment.Results:Among 45 patients with moderate to severe atopic dermatitis complicated with asthma, after treatment with dupilumab, the FEV 1 increased from 2.39 (1.87, 2.83) L at baseline to 2.50 (1.84, 2.97) L 3 months after treatment ( Z=2.417, P=0.016), 2.60 (1.95, 3.14) L 6 months after treatment ( Z=2.896, P=0.004); the FEV 1pred% increased from 74.10% (67.70%, 78.75%) at baseline to 77.09% (68.40%, 80.24%) at 3 months after treatment ( Z=2.574, P=0.010), and 77.20% (71.10%, 80.72%) at 6 months after treatment ( Z=2.861, P=0.004). Meanwhile, there were statistically significant differences in the ACT and Mini-AQLQ scales at 3, 6, and 12 months after treatment compared with those before treatment (ACT score Z=3.170, 4.216, 5.723; Mini-AQLQ score Z=3.231, 4.133, 5.826; all P<0.05). The EASI scale decreased from baseline 25.90 (18.95, 33.45) to 6.20 (1.15, 8.35) at 4 months after treatment ( Z=5.842, P<0.05) and 4.90 (2.75, 8.35) at 6 months after treatment ( Z=5.841, P<0.05), 4.00 (3.15, 5.05) at 12 months after treatment ( Z=5.841, P<0.05); The scores of each scale of IGA, NRS and DLQI decreased significantly compared with the baseline after 4 months, 6 months and 12 months of treatment, and this trend became more obvious with the extension of treatment time. The differences were statistically significant (IGA score Z=6.247, 6.070, 5.946; NRS score Z=5.960, 5.893, 5.879; DLQI score Z=5.880, 5.850, 5.848; all P<0.05). During treatment, 1 patient had local adverse reactions at the injection site and 1 patient had conjunctivitis. Conclusion:Dupilumab may have a positive effect on improving the clinical efficacy of patients with moderate to severe atopic dermatitis complicated with asthma. During the 12-month observation period, this biological agent generally demonstrated good safety characteristics.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 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 Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated 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 thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Objective:To investigate the relationship among iron content, volume and drainage venous oxygen saturation (SvO 2) in deep gray matter nuclei of healthy people using quantitative susceptibility mapping (QSM). Methods:The study was a cross-sectional study. A total of 126 healthy volunteers were prospectively enrolled in the community in Tianjin from June 2019 to December 2023, and 57 males and 69 females, aged 48±15 years. All healthy volunteers underwent MRI examinations to get STrategically Acquired Gradient Echo images, then it was post-processed to obtain T 1 weighted enhanced images, QSM maps and the maximum intensity projection images. In QSM maps, caudate nucleus (CN), putamen (PUT), globus pallidus (GP), thalamus (THU), subthalamic nucleus (STN), substantia nigra (SN) and red nucleus (RN) were semi-automatically segmented to calculate the iron content and volume using SPIN software. Four bilateral deep cerebral veins regions of interest, including septum pellucidum veins, thalamostriate veins, internal cerebral veins and basilar veins, were manually delineated on the maximum intensity projection images of QSM to obtain venous magnetic sensitivity. The venous magnetic sensitivity was calculated as SvO 2. To observe the age-related trend of SvO 2, iron content and volume, the partial correlation analysis was conducted. The relationships between iron content, volume and SvO 2 were explored using the partial correlation analysis. To explore the potential effects of SvO 2 between iron content and volume in deep gray matter, the mediation analysis was utilized. Results:The relationships between the SvO 2 of thalamostriate veins ( r=0.23, P=0.018), basilar veins ( r=0.27, P=0.004) and age were positive. The relationships between the SvO 2 of internal cerebral veins and the iron contents of CN ( r=?0.25, P=0.042) and PUT ( r=?0.33, P<0.001) were negative. The relationships between the SvO 2 of basilar veins and the iron contents of STN ( r=?0.25, P=0.042) and SN ( r=?0.24, P=0.045) were negative. The relationships between iron content and volume including CN ( r=0.46, P<0.001), PUT ( r=0.20, P=0.027), GP ( r=0.76, P<0.001), STN ( r=0.87, P<0.001), SN ( r=0.90, P<0.001), RN ( r=0.79, P<0.001) were positive. The mediation analysis showed that the SvO 2 of internal cerebral veins indirectly mediated the relationship between iron content and volume of CN, PUT, GP and THU. Conclusions:The process of iron deposition required the participation of oxygen in deep gray matter nuclei. Volume shows positive correlation with iron content in deep gray matter nuclei, with individual variations. The SvO 2 of internal cerebral veins mediate the relationship between iron content and volume of deep gray matter nuclei.

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.