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*

Aim To investigate the impact of G pro-tein-coupled estrogen receptor 1(GPER1),also known as GPR30 playing a significant role in the nerv-ous system,on neuronal damage and cognitive dysfunc-tion following epileptic seizures.Methods The pro-tein expression levels of GPER1 and the DNA damage marker γ-H2AX in epileptic rats were assessed using Western blot.The hippocampal neuronal damage and apoptosis in pilocarpine-induced epilepsy models were evaluated using Nissl and TUNEL staining techniques,compared with GPER1 knockdown(GPER1-KD)rats with wild-type(WT)controls.The behavioral activi-ties,including memory and spatial learning,were mo-nitored during the chronic phase of epilepsy using the IntelliCage system.Results Compared to the control group,GPER1 protein expression in the cerebral cortex and hippocampus significantly increased 24 hours post-epilepsy onset.In the GPER1-KD+EP group,hipp-ocampal neuronal damage was more severe,with a sig-nificant increase in apoptotic neurons compared to the WT+EP group.The IntelliCage data revealed that during free exploration,nose contact,position learn-ing,and reverse position learning stages in the GPER1-KD+EP group exhibited fewer visits and a higher error rate than in the WT+EP group.Conclu-sions Deficiency in GPER1 impairs memory and spa-tial learning abilities following epilepsy,potentially due to exacerbated neuronal injury,apoptosis,and inflam-mation.GPER1 represents a promising therapeutic tar-get for mitigating post-epileptic nerve damage and cog-nitive impairment.

A patient with anti-MDA5-positive dermatomyositis complicated by hepatic dysfunction developed rhabdomyolysis after an intravenous injection of gadopentetate dimeglumine for magnetic resonance imaging.Analysis of clinical manifestations and medication correlation confirmed gadopentetate dimeglumineinduced rhabdomyolysis.Gadopentetate dimeglumine can cause rhabdomyolysis in dermatomyositis patients.Clinical conditions should be closely monitored when using gadopentetate dimeglumine to guard against adverse reactions.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

OBJECTIVE: To explore the relationship between the geriatric nutritional risk index (GNRI) and cognitive function. METHODS: A cross-sectional study method was conducted. People aged ≥ 60 years from the National Health and Nutrition Examination Survey (NHANES) databases from 1999 to 2002 and 2011 to 2014 were included as study subjects. The participants were divided into three groups based on their GNRI scores: a medium-high risk group (82 ≤ GNRI < 92), a low risk group (92 ≤ GNRI < 98), and a no-risk group (GNRI ≥ 98). Demographic characteristics (gender, age, race, education), chronic diseases [chronic bronchitis, emphysema, thyroid problems, coronary heart disease, angina pectoris, stroke, hypertension, diabetes mellitus, and depression score on the patient health questionnaire (PHQ-9)], lifestyle habits (history of smoking, hours of sleep), etc., were collected. Cognitive function was assessed using the consortium to establish a registry for Alzheimer's disease word learning subtest (CERAD-WL), animal fluency test (AFT), and digit symbol substitution test (DSST) for the 2011-2014 data, while only the DSST was used for the 1999-2002 data. Differences in the above information among the GNRI cohorts were compared. Factors affecting cognitive function in the population were analyzed using multifactorial Logistic regression. RESULTS: 2 653 participants from 2011 to 2014 and 2 380 participants from 1999 to 2002 were enrolled, with a total of 5 033 participants in the study. There were statistically significant differences in age, stroke, diabetes mellitus, DSST score, AFT score, CERAD score test 1 recall (Cst1), and CERAD score test 2 recall (Cst2) among the GNRI groups. Multifactorial Logistic regression analysis of data from 2011 to 2014 showed that in model 3 (DSST score, age, gender, race, marriage, education, hours of sleep, history of smoking, emphysema, thyroid problems, chronic bronchitis, coronary heart disease, angina pectoris, hypertension, diabetes mellitus, depression score on the PHQ-9, and stroke) adjusted for all covariates, GNRI was a protective factor for DSST [odds ratio (OR) = 1.03, 95% confidence interval (95%CI) was 1.00 to 1.05, P = 0.03]; Logistic regression analyse for 1999 to 2002 and 2011 to 2014 showed a significant association even after adjustment for covariates (OR = 1.02, 95%CI was 1.00 to 1.03, P = 0.02). Subgroup Logistic regression analyses of the total population from 2011 to 2014 showed a significant association between GNRI and DSST scores (OR = 1.02, 95%CI was 1.01 to 1.03, P < 0.001), with significant associations in the age subgroups of 60 to 64 years old, across gender, non-Hispanic Whites and Blacks, by education, and by marital status associations were significant (all P < 0.05). Subgroup Logistic regression analyse of the total populations from 1999 to 2002 and 2011 to 2014 showed a significant association between the GNRI and DSST score (OR = 1.01, 95%CI was 1.01 to 1.02, P < 0.001), but did not show a significant year difference (interaction P = 0.503), and the newly found in the smoking population the association was also more significant (P < 0.01). CONCLUSION The GNRI correlates with the presence of cognitive functions related to processing speed, sustained attention, and executive function, and may be able to serve as an indicator for the assessment or prediction of related cognitive functions.
Humans ; Cross-Sectional Studies ; Aged ; Middle Aged ; Nutrition Surveys ; Cognition ; Female ; Male ; Nutritional Status ; Risk Factors ; Geriatric Assessment

Objective To investigate the density,species composition,and seasonal prevalence of domestic rodents in different habitats within Lanzhou garrisons,providing basic information for rodent prevention and control.Methods A total of 12 monitoring sites were sampled across urban,suburban,and rural residential areas from 2014 to 2022.Rodent density was monitored using the night-trapping method in the middle of odd-numbered months.Results From 2014 to 2022,346 domestic rodents were captured using 122 035 effective traps,with an average domestic rodent density of 0.28％.The highest domestic rodent density was 0.63％in 2016,and the lowest was 0.07％in 2020,showing significant differences across years,with an overall trend of initially decreasing and then increasing(χ2=136.555,P<0.001).The dominant species was Rattus norvegicus,accounting for 83.24％of the total rodents captured.Rattus norvegicus accounted for a relatively high proportion across different years,with a statistically significant difference in species composition(χ2=20.931,P<0.05).Rodent densities and species composition also varied significantly among the monitored habitats(P<0.001),with the highest densities observed in rural residential areas and the lowest in urban areas.Seasonal variation in rodent densities showed a bimodal pattern,with smaller peaks in January or March and a larger peak in July.Conclusions Domestic rodent density in Lanzhou garrisons has shown an upward trend in the past few years.Rodent control measures should focus on barracks in rural residential areas,with targeted interventions to reduce the risk of rodent-borne diseases.

Objective:To explore the application effect of fine skin care in patients with psoriasis, and provide evidence-based theoretical basis for the development of skin care in patients with psoriasis.Methods:A randomized controlled trial was conducted. Patients with psoriasis admitted to the People′s Hospital of Wenshan Zhuang and Miao Autonomous Prefecture, Yunnan Province from December 2022 to March 2024 were selected as the research subjects by the convenience sampling method and divided into the control group and the experimental group by the random number table method. The control group was given routine care. The experimental group was given fine skin care on the basis of control group. Before and after the intervention, the itching symptoms, skin lesions, comfort and quality of life were evaluated using 12-item Pruritus Severity Scale (12-PSS), Psoriasis Area and Severity Index (PASI), General Comfort Questionnaire (GCQ), 36-item Short Form (SF-36) and compared between the two groups. The incidence of complications and recurrence rate in the two groups were counted 3 months after intervention.Results:Finally, 96 patients were included in the study, including 48 patients in the experimental group, 28 males and 20 females, aged (59.31 ± 17.31) years old; 48 cases in the control group, 29 males and 19 females, aged (61.54 ± 18.11) years old. Before the intervention, there were no statistically significant differences in the scores of 12-PSS, PASI, GCQ and SF-36 between the two groups (all P>0.05). After the intervention, the scores of 12-PSS and PASI in the experimental group were (3.65 ± 2.96), (5.08 ± 1.15) points respectively, which were lower than (8.29 ± 2.00), (7.37 ± 1.34) points in the control group, the differences were statistically significant ( t=9.00, 8.99, both P<0.05). The scores of GCQ and SF-36 in the experimental group were (41.42 ± 4.01), (95.08 ± 4.47) points respectively, which were higher than (33.94 ± 5.74) and (84.19 ± 8.52) points in the control group, the differences were statistically significant ( t=7.40, 7.84, both P<0.05). The total incidence of complications and recurrence rate in the experimental group were 4.17% (2/48), 2.08% (1/48) respectively, which were lower than 18.75% (9/48), 14.58% (7/48) in the control group, the differences were statistically significant ( χ2=5.03, 4.91, both P<0.05). Conclusions:Fine skin care can improve the itching symptoms of patients with psoriasis and reduce the severity of skin lesions. It can also improve the comfort and quality of life of patients and reduce the incidence of complications and recurrence rate, and the clinical application effect is good.