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*

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

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Fifteen compounds(1-15) were isolated from the 95% EtOH extract of the whole herb of Physalis minima by various chromatography techniques including silica gel, Sephadex LH-20, middle chromatogram isolated gel(MCI), octadecyl silica(ODS), and semi-preparative high performance liquid chromatography(HPLC). Their structures were elucidated by infrared spectroscopy(IR), ultraviolet spectroscopy(UV), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), nuclear magnetic re-sonance(NMR), and circular dichroism(CD) as(5S)-5,11-dihydroxy-3-methyl-5-pentylfuran-2(5H)-one(1), withaphysalin R(2), withaphysalin Q(3), withaphysanolide A(4), phaseic acid(5), grasshopper ketone(6), 3S,5R-dihydroxy-6S,7-megastigmadien-9-one(7), vanillic acid(8), 2-trans,4-trans-abscisic acid(9), capillasterolide(10), 5,3'-dihydroxy-3,7,4'-trimethoxyflavone(11),(-)-loliolide(12), 4-hydroxyacetophenone(13), acetosyringone(14), and aurantiamide acetate(15). Compound 1 was a new butenolide, and compounds 5-7 and 10-12 were isolated from the Physalis for the first time. Compounds 4, 13, and 15 were isolated for the first time from P. minima. Moreover, their anti-inflammatory activity was evaluated in vitro. Compound 12 was found to possess an inhibitory effect on the transcription of an NF-κB-dependent reporter gene in LPS-induced 293 T/NF-κB-luc cells at 10 μmol·L~(-1), showing an inhibitory rate of 62.31%±4.8%.
Anti-Inflammatory Agents ; Chromatography, High Pressure Liquid ; NF-kappa B ; Physalis ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVE: To explore the effect of bone morphogenetic protein 4(BMP4) on the cell cycle and apoptosis of hemaropoictic stem and progenitor cells (HSPC) in conditions of 5-fluorouracil (5-FU)-inducing bone marrow suppression and stress hemogenesis, and its possible mechanism. METHODS: The C57BL transgenic mice with BMP4 overexpression were established and were enrolled in transgenic group (BMP4 group), at the same time the wild type mice matching in age, sex and body weight were selected and were enrolled in control group (WT group). The bone marrow suppression was induced by injection with 5-FU in dose of 150 mg/kg, then the nucleated cells were isolated from bone marrow. After the HSPCs were markered with C-kit/sca-1 fluorescent antibodies, the changes of cell cycle and apoptosis of HSPC were detected by Aunexin V/PI and Ki67/DAPI double staining; the cell cycle-essociated hemotopoietic regulatory factors were detected by RT-qPCR. RESULTS: Under physiologic status, there were no significant differences in cell cycle and apoptotic rate of HSPC between WT group and BMP-4 group. After the bone marrow was suppressed, the ratio of HSPC at G0 phase in BMP4 group significantly decreased(P＜0.05); the apoptosis rate of HSPC significantly increased(P＜0.05); the mRNA expression levels of hypoxia-inducing factor Hif-1α and chemotactic factor CXCL12 in stroma of BMP4 group were down-regulated significanfly(P＜0.05). CONCLUSION Under non-physiologic conditions such as stress hemogenesis or bone marrow suppression, the up-regulation of BMP4 can promote HSPC into cell cycle and apoptosis of HSPC, moreover, the BMP4 may play a regulatory role for cell cycle of HSPC through direct or indirect down-regulation of Hif-1α and CXCL-12 expressions.
Animals ; Antineoplastic Agents ; Apoptosis ; Bone Morphogenetic Protein 4 ; Cell Cycle ; Hematopoietic Stem Cells ; Mice ; Mice, Inbred C57BL

Objective To understand the humanistic concern ability of nurses with low seniority (less than 5 years)so as to establish a high-quality training platform centred on cultivating humanistic concern ability of them for proving high quality care for patients.Methods A total of 94 nurses with low seniority were investigated with the self-designed questionnaire and caring ability inventory (CAI)in a class-three grade A hospital of Jinan.Results The total score and score of each dimension of humanistic concern ability in nurses with low seniority were lower than norm abroad (P <0.05).The score of cognition and patience in nurses with seniority less than 2 years were higher than those in nurses with seniority between 2 and 5 years with significant differences (P <0.05);however,the score of courage in nurses with seniority less than 2 years was lower than that in nurses with seniority between 2 and 5 years along with a significant difference (P <0.05).The wage level had an impact on humanistic concern ability of nurses with low seniority (P <0.05).Conclusions The level of humanistic concern ability of nurses with low seniority was low with significant differences in seniority and wage level.Humanistic concern education in junior nurses should be paid more attention to.Humanistic concern ability of nurses with low seniority can be improved by relevant training of humanistic concern,raising wages and so on.

Objective To detect the volume changes of cerebral gray and white matter in patients with maintaining hemodialysis using voxel-based morphometry(VBM) and to correlate these changes with cognitive function. Methods Forty-two patients with maintaining hemodialysis and 41 age and sex matched normal subjects were recruited in this study. MMSE was obtained to evaluate their neuropsychiatric conditions. Whole brain high-resolution T1WI was performed on 3.0 T MR scanner in both patients and normal controls. The data were analyzed by VBM based on SPM8, using analysis of functional neuroimages (AFNI) software package with the Monte Carlo simulation method(AlphaSim method) for multiple cluster level comparisons correction. Independent sample t test analysis was used to compare the volume of gray and white matter between the patients and normal controls. In addition, Stepwise multiple linear regression analysis was performed to explore the correlation between the voxel value of cerebral volume changes area and dialysis duration and clinical laboratory examination, and Spearman correlation analysis was used for the correlation between the left insula voxel values and neuropsychological test scores. Results Compared with normal controls, patients showed significantly decreased volume in the grey matter of the right putamen, the left putamen, the left insula (numbers of voxel in clusters were 455, 561, 162, t=-9.5681,-5.9516,-5.7185,P<0.001, AlphaSim-corrected). There was negative correlation between decreased grey matter volume of the right putamen[(0.53 ± 0.12)mm3]and the left putamen[(0.48 ± 0.12)mm3] and dialysis duration [19.0(1.5-114.0)months] (r=-0.330,-0.307,P<0.05). MMSE score of patients[29(21-30)score] was significantly lower than normal controls[30(28-30)score] (Z=-30.58,P<0.01). Decreased grey matter volume of the left insula [(0.39 ± 0.12) mm3] was positively correlated with MMSE(r=0.320, P<0.05). Conclusions The patients with maintaining hemodialysis show grey matter atrophy which is associated with neurocognitive dysfunction. Dialysis duration may be an important risk factor for decreased gray matter in patients with maintaining hemodialysis.

Objective To evaluate the distribution and age-related changes of brain iron content in healthy people using MR quantitative susceptibility mapping (QSM).Methods Sixty three healthy right-handed volunteers underwent the routine MRI and SWI scan to get SWI-unfiltered phase images and magnitude images.QSM were reconstructed from the SWI-unfiltered phase images and magnitude images using SMART software.The regions of interest at the bilateral frontal white matter and nuclei (caudate nuclews,globus pallidus,putamen,substantia nigra,dorsal thalamus,red nucleus and dental nucleus) were drawn manually,and the susceptibility was measured.The linear correlation between the susceptibility and iron concentration cited from Hallgren and Sourander's post-mortem brain study was calculated.Wilcoxon test were applied to calculate the difference between the bilateral frontal white matter and bilateral nuclei.The correlation of age with susceptibility of bilateral frontal white matter and bilateral nuclei were analyzed by Spearman correlation analysis.Results The median susceptibility (extent) of frontal white matter,caudate nucleus,globus pallidus,putamen,dorsal thalamus,substantia nigra,red nucleus and dentate nucleus of 63 healthy people were-12.81 (-31.56,8.72),39.27 (22.35,75.13),93.99 (19.19,158.75),29.16 (4.11,81.53),2.91 (-27.80,27.95),83.14 (38.57,185.79),63.49 (13.83,142.09),63.30 (36.78,128.53) ppb (× 10-9),respectively.There was high consistency with Hallgren and Sourander's study (r=0.91,P＜0.05).The susceptibility of globus pallidus was the highest,followed by substantia nigra.The least susceptibility was seen in the frontal white matter.The susceptibility of right caudate nucleus,substantia nigra,red nucleus and dental nucleus was higher than that of left side (Z value was-3.18,-4.44,-3.70 and-2.64,respectively,P＜0.05).The susceptibility of bilateral globus pallidus of the male was significantly different from that of the female (Z value was-2.27 and-2.42,respectively,P＜0.05).There was positive correlation between age and the susceptibility of bilateral caudate nucleus,putamen,red nucleus and dental nucleus (r value was 0.30 to 0.49,P＜0.05).Conclusions QSM based on the SWI-unfiltered phase and magnitude images can clearly display the cerebral nuclei and evaluate the brain iron content accurately,which is consistent with the histopathological results.Iron content of bilateral caudate nucleus,putamen,red nucleus and dental nucleus increase with aging.

OBJECTIVE: To investigate the feasibility of a novel molecular probe of Zn-DPA-PSS794 to monitor the efficiency of doxorubicin to ovarian cancer and compare with Cy5.5-annexin V. METHODS: Efficiency of doxorubicin to OVCAR-8 cells in vitro was measured by MTT assay and flow cytometry. The in vivo studies were performed on an OVCAR-8 xenograft tumor model. Mice were divided into a control group and a treatment group. Each group was divided into 2 subgroups, DPA and annexin V. In the treatment group, the mice were treated with doxorubicin for 2 doses. All mice were performed optical imaging by Zn-DPA-PSS794 or Cy5.5-annexin V, respectively and then sacrificed. The tumor was separated and stained by HE. The expression of caspase-3 protein was measured by Western blot. RESULTS: The IC50 of doxorubicin to OVCAR-8 was 6 μmol/L. The percentage of apoptosis and dead cells was 35% after doxorubicin treatment. In the optical image, photons accumulated in the tumor either by Zn-DPA-PSS794 or Cy 5.5-annexin V in the treatment group. That was negative in the control group. The fluorescence intensity had significant difference between the 2 groups(P<0.001). The nuclei were big and stained with deep color after the cells were stained with HE. The caspase-3 expression was high in the treatment group, while it was low in the control group. CONCLUSION Zn-DPA-PSS794 as a probe used by optical imaging can monitor the efficiency of doxorubicin to OVCAR-8 xenograft tumor, which is similar to Cy5.5-annexin V.
Animals ; Apoptosis ; drug effects ; Carbocyanines ; Cell Line, Tumor ; Doxorubicin ; pharmacology ; Female ; Fluorescent Dyes ; Humans ; Infrared Rays ; Mice ; Mice, Nude ; Molecular Imaging ; Organometallic Compounds ; Ovarian Neoplasms ; pathology ; Picolines ; Spectroscopy, Near-Infrared ; methods

AIMTo study the influence of astragalus and zinc sulfate on the viscosity in erythrocyte membrane during intestinal I/R and their mechanism of action.

METHODSModels of rabbits intestinal I/R injury were made. The effect of astragalus and zinc sulfate on the viscosity and malondialdehyde (MDA) in erythrocyte membrane, superoxide dismutase (SOD) in erythrocyte, oxidase (XO) in plasma and MDA tissues homogenate were observed.

RESULTSThe administration of astragalus and zinc sulfate decreased viscosity and MDA and XO, prevented the reduction of SOD, and alleviated I/R injury.

CONCLUSIONLipid peroxidation injury of the erythrocyte membrane was one of the pathogenesis of I/R injury, and astragalus and the zinc sulfate possessed effects of anti-lipid peroxide, stabilized erythrocyte membrane, increased red blood cell deform ability and raised microcircular perfusion.

Animals ; Astragalus Plant ; Blood Viscosity ; Drugs, Chinese Herbal ; pharmacology ; Erythrocyte Membrane ; drug effects ; Female ; Intestines ; blood supply ; pathology ; Lipid Peroxidation ; Male ; Malondialdehyde ; analysis ; Oxidoreductases ; analysis ; Rabbits ; Reperfusion Injury ; metabolism ; pathology ; Superoxide Dismutase ; analysis ; Zinc Sulfate ; pharmacology