OBJECTIVE: To analyze a Chinese pedigree affected with Non-syndromic autosomal recessive deafness type 12 (NFNB12), validate the function of candidate variants, and explore the underlying mechanisms. METHODS: A NFNB12 pedigree presented at Henan Provincial People's Hospital in February 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing of the pedigree members. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the level of mRNA transcription in the peripheral blood samples from the pedigree members, and protein expression was evaluated with Western blotting assay. This study was approved by Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2019-134). RESULTS: WES analysis revealed that the proband has harbored homozygous c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene, for which both parents were identified as heterozygous carriers. RT-PCR analysis demonstrated the sole presence of the variant mRNA in the proband, and both the variant and wild-type mRNAs in both parents. Furthermore, Western blotting analysis indicated that the proband had exclusively expressed the truncated CDH23 protein, while both the normal and truncated forms of the protein were noted in her parents. CONCLUSION The c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene probably underlay the pathogenesis of NFNB12 in this pedigree. The loss of function of the CDH23 gene resulting from this variant is not related with nonsense-mediated mRNA decay, but rather production of a truncated protein. Above finding has not only enriched the mutational spectrum of the CDH23 gene and offered a method for investigating the function of its variants using peripheral blood samples, but also delineated the molecular basis for the loss of function, which has provided crucial evidence for genetic counseling and prenatal diagnosis for this family.
Humans ; Pedigree ; Male ; Female ; Asian People/genetics* ; Cadherins/genetics* ; Exome Sequencing ; Deafness/genetics* ; Mutation ; China ; Adult ; Cadherin Related Proteins ; Hearing Loss, Sensorineural/genetics* ; East Asian People

This study aims to understand the epidemic distribution characteristics,antimicrobial resistance,virulence genes,and biofilm adhesion ability of Enterococcus in yaks on the Tibetan plateau.Three hundred and forty-six fresh yak fecal samples and 311 milk samples were collected from four provinces on the Tibetan plateau(Xizang,Sichuan,Gansu,Qinghai),totaling 657 sam-ples.Bacterial isolation and identification were conducted,followed by 16S rDNA gene detection and the construction of a systematic evolutionary tree.The isolated strains were tested for antimi-crobial resistance and virulence genes using PCR,and sensitivity tests were performed using 18 types of antibiotics.The biofilm adhesion ability of the isolated bacteria was determined using an improved semi-quantitative crystal violet staining method.The results showed that the total isola-tion rate of Enterococcus was 32.27％,with Sichuan having the highest at 60.23％,followed by Gansu,Qinghai,and Tibet autonomous region at 42.70％,23.47％,and 18.31％respectively.In terms of sample types,the isolation rate in fecal samples was 36.71％,and in milk samples,it was 27.33％.Through PCR amplification,bands of approximately 1 400 bp were obtained,and 5 strains were selected for evolutionary analysis,forming a separate cluster.Among the 212 isolated strains,a high resistance to clindamycin,quinupristin-dalfopristin,linezolid,levofloxacin,and erythromycin was observed,with various resistance phenomena,accounting for 60.85％.Only 5 out of 12 resist-ant genes were detected,namely erm(B),tet(L),tet(O),tet(M),and ant(6)-Ia.All 13 virulence genes were detected in Enterococcus,with detection rates in the range of 5.19％to 95.76％,where cpd was 95.75％,gelE was 91.98％,efaA was 86.79％,asal was 86.32％,and the rest ranged from 5.19％to 55.66％.The fsr virulence gene was not detected in Enterococcus from milk sources.Among the isolated strains,3.30％showed medium adhesive ability,48.58％showed weak adhesive ability,and 48.11％showed no adhesive ability.The above research revealed the preva-lence of yak derived Enterococcus,the carrying status of resistance and virulence genes,and the correlation between biofilm phenotypes,laying the foundation for mastering research data on yak-derived Enterococcus in the Tibetan plateau.

Investigated the mechanisms by which baicalein regulates nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)to ameliorate lipopolysaccharide(LPS)-induced sepsis-asso-ciated acute kidney injury(AKI)in mice.Sixty male C57BL/6 mice were randomly divided into six groups:control,model,low-dose baicalein(50 mg/kg),medium-dose baicalein(100 mg/kg),high-dose baicalein(200 mg/kg),and high-dose baicalein+brusatol(4 mg/kg).Baicalein was adminis-tered orally for 7 days as a preventative measure.Sepsis was induced via intraperitoneal injection of LPS.Murine sepsis score(MSS)was assessed within 12 hours post-induction.Serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an automatic biochemical analyzer and enzyme-linked immunosorbent assays(ELISA),respectively.Histopathological changes in kidney tissues were ob-served via hematoxylin-eosin(HE)staining.Western blot analysis was employed to determine the protein expression levels of Nrf2,HO-1,caspase-8,TNF-α,IL-1β,and IL-6 in kidney tissues.Additionally,total superoxide dismutase(SOD)activity in kidney tissues was assessed using com-mercially available kits.Compared to the model group,baicalein treatment significantly improved renal histopathological changes,alleviated cellular damage,and reduced the levels of inflammatory cytokines(TNF-α,IL-1βand IL-6)(P＜0.01)and kidney injury markers(Scr and BUN)(P＜0.01).Moreover,baicalein treatment significantly increased the protein expression levels of Nrf2 and HO-1(P＜0.01)and enhanced antioxidant enzyme activity.In conclusion,baicalein may pro-tect against LPS-induced sepsis-associated AK1 in mice by modulating the Nrf2/HO-1 signaling pathway,thereby attenuating oxidative stress,reducing inflammation,and disrupting the vicious cycle between inflammation and oxidative stress.

Objective:To explore the interrelationship between brain functional networks and features in functional magnetic resonance imaging(fMRI)of patients with Alzheimer's disease(AD),and to construct mixed-function networks(MFN),and apply them in machine learning classification models to improve the accuracy of AD classification.Methods:102 AD patients and 227 healthy subjects in the Alzheimer's Neuroimaging Initiative(ADNI)dataset were retrospectively analyzed.The partial correlation brain network of the blood oxygen level dependent(BOLD)signal was calculated and fused with low-frequency wave amplitude(ALFF),fractional low-frequency wave amplitude(fALFF)and local consistency(ReHo)features to construct MFN.Network topology parameters were extracted,and a variety of machine learning classification models were constructed based on MFN topological parameters,accuracy,precision,recall and area under the curve(AUC)were used to evaluate the predictive efficiency of the models.Results:By constructed MFN and calculated intra group to inter group ratio(IIGR),35 features could be obtained from ALFF,fALFF and ReHo feature topological parameter analysis,after rank sum test and FDR correction,there were statistical differences among 28 features(P＜0.05).The classification results show that,all the five classifiers have high classification performance on the test data set.The accuracy,precision and recall rates of random forest(RF),adaptive lifting algorithm(AdaBoost),guided aggregation algorithm(Bagging)and support vector machine(SVM)were all 99.7％,and the AUC values were up to 100％,99.5％,99.1％and 99.5％,respectively.The accuracy(98.5％),precision(98.5％),recall(98.5％),and AUC(99.1％)of the multi-layer perceptron(MLP)were slightly lower than other models,but remained excellent.It was worth noting that RF has the highest AUC value of all models at 100.0％,while Bagging has the lowest AUC value(99.1％)in the integrated approach.The results of performance comparison show that,MFN classification model can significantly improve the recognition and classification of AD disease,and greatly improve the performance of various indicators of the classifier.The results showed that,MFN classification model was superior to intelligent classification based fusion,DBN-based multitask learning,PVT-TSVM,unsupervised learning and clustering,SVM and SVM of degree 3 polynomial kernel function in key indicators such as accuracy(99.13％),AUC(99.42％),recall rate(99.46％)and specificity(99.42％)with plasma proteins,machine learning algorithms.It was further proved that MFN classification model has good generalization ability and robustness in AD disease classification.Conclusion:The AD classification model constructed based on brain mixed function network topology parameters and machine learning can improve the accuracy of AD classification.

Cognitive decline is one of the most common adverse symptoms following acute high-altitude exposure(AHAE).MRI can reveal the structural and functional changes in brain caused by AHAE,thereby deeply understanding the specific mechanism of its cognitive decline,which is of great significance for early prevention and intervention.Research progresses on MRI assessment of cognitive function after AHAE and related intervention methods were reviewed in this article.

Special environments have significant impacts on the structure and function of multiple organs in human body,thereby causing a series of physiological or pathological adaptive changes.Imaging represents a pivotal technological approach for visualizing the structural damage and functional changes in organs.The research progresses of multi-organ imaging in special environments were reviewed in this article.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:The aim of this study is to evaluate the clinical efficacy of Oxalicao Formula combined with transacu-puncture in the treatment of chronic nonbacterial prostatitis(CNP)characterized by dampness-heat stasis.Methods:A total of 70 patients diagnosed with CNP and characterized by dampness-heat stasis were randomly divided into control group and treatment group,with 35 cases in each group.The patients in control group received Qianlie Beixi capsules.While the patients in treatment group were administered with oxalis decoction in conjunction with acupuncture therapy which lasted for 8 weeks.Pre-and post-treatment evalua-tions for NIH-Chronic Prostatitis Symptom Index(NIH-CPSI),Traditional Chinese Medicine(TCM)symptom scores,urodynamic pa-rameters,immune cell subsets and inflammatory factors were performed.Results:Ultimately,65 patients completed the study with 33 in the treatment group and 32 in the control group.After 8 weeks of intervention,the patients in both of groups demonstrated signifi-cant improvements(P＜0.05).Specifically,remarkable reductions in the NIH-CPSI total score including pain score,urination score,quality of life impact score,TCM symptom score and inflammatory cytokine levels were observed.Additionally,there were upward trends in maximum and average urinary flow rates as well as the CD4+/CD8+ratio of immune cells(P＜0.05).Compared to the con-trol group,the treatment group exhibited superior outcomes in reducing the NIH-CPSI total score,pain score,urination score,quality of life impact score,TCM symptom score,and inflammatory cytokine levels,and increasing in CD4+/CD8+ratios,maximum and av-erage urine flow rates(P＜0.05).Conclusion:The combination of Oxalicao Formula and transacupuncture for treating CNP charac-terized by dampness-heat stasis demonstrates significant therapeutic benefits,which has considerable clinical application value.

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.