BACKGROUND:Differentially expressed RNA-binding proteins in the intervertebral disc plays a key role in intervertebral disc degeneration,and decreased levels of the RNA-binding protein KRT18 are associated with degenerative disc disease,but its specific role in the nucleus pulposus cells has not yet been fully determined. OBJECTIVE:To investigate the interaction of KRT18 with mRNA and long non-coding RNA on nucleus pulposus cells of the intervertebral disc and its mechanism. METHODS:Normal and degenerated nucleus pulposus cells were obtained from nucleus pulposus samples of patients undergoing interbody fusion for lumbar fracture or intervertebral disc degeneration.iRIP-seq,functional enrichment analysis,and DNA microarray analysis were performed to identify the mRNA and long non-coding RNA binding with KRT18.Subsequently,KRT18 was knocked down in nucleus pulposus cells based on the analysis results,and the expression levels of related genes were detected at the protein and RNA levels through protein immunoblotting and qRT-PCR,respectively. RESULTS AND CONCLUSION:Through iRIP-seq analysis,we identified abundant KRT18 binding sites within the GUAAUC and AGCCUC sequences,indicating that KRT18 may be involved in regulating RNA transcription,translation,stability or play a role in cell signaling pathways.It can stably bind to mature mRNA,among which highly expressed genes include CRLF1,IGFBP4,etc.At the same time,the peak genes of long non-coding RNA binding with it include SNHG25,SNHG12,NEAT1,USP32,EIF4A2 and CDH4.Most of these genes are involved in various biological processes such as apoptosis and inflammation,and can mediate related pathways of extracellular matrix metabolism.KRT18 can regulate their stability,transport,translation,splicing and other functions,thus affecting gene expression and cell function.We further verified through experiments the knockdown of KRT18 in nucleus pulposus cells,and found that the level of extracellular matrix metabolism was inhibited and unbalanced,resulting in intervertebral disc degeneration in vitro.This study investigated the regulatory mechanism of KRT18 from the perspective of its binding with mRNA and long non-coding RNA for the first time,and speculated the potential function of KRT18 in the pathogenesis of intervertebral disc degeneration,laying a foundation for future research on the key functions of KRT18.

Voice biomarkers， as an emerging smart medical technology， are now being used in applications such as assisting in the diagnosis and treatment of diseases， facilitating accurate and personalized medical services for patients. However， it also raises many ethical issues， including informed consent， privacy protection， accuracy and reliability， data security， legal risks， and other issues. This paper systematically sorted out the ethical issues in the applications of voice biomarkers in the medical field， summarized these issues， such as informed consent， privacy protection， accuracy and reliability， data security， and legal risks， as well as explored the corresponding coping strategies. These countermeasures encompassed utilizing new media platforms to raise public awareness of voice biomarkers， strengthening supervision and management to promote the privacy protection of voice biomarkers， reducing algorithm biases to promote the general benefits of voice biomarkers to the public， establishing multidisciplinary teams to protect the data security of voice biomarkers， and encouraging medical professionals and researchers to participate in policy research， with a view to providing references for promoting and regulating the applications of voice biomarkers in the medical field.

The existing epilepsy seizure detection algorithms have problems such as overfitting and poor generalization ability due to high reliance on manual labeling of electroencephalogram's data and data imbalance between seizure and interictal periods. An unsupervised learning detection method for epileptic seizure that jointed graph attention network (GAT) and Transformer framework (GAT-T) was proposed. In this method, channel correlations were adaptively learned by GAT encoder. Temporal information was captured by one-dimensional convolution decoder. Combining outputs of the two mentioned above, predicted values for electroencephalogram were generated. The collective anomaly score was calculated and the detection threshold was determined. The results demonstrated that GAT-T achieved the average performance exceeding 90% (or 99%) with a 0.25 s (or 2 s) time segment length, which could effectively detect epileptic seizures. Moreover, the channel association probability matrix was expected to assist clinicians in the initial screening of the epileptogenic zone, and ablation experiments also reflected the significance of each module in GAT-T. This study may assist clinicians in making more accurate diagnostic and therapeutic decisions for epilepsy patients.
Humans ; Electroencephalography/methods* ; Epilepsy/physiopathology* ; Algorithms ; Seizures/physiopathology* ; Neural Networks, Computer ; Signal Processing, Computer-Assisted

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Objective To study the effect of dexmedetomidine(DEX)on TNF-α-induced injury of human neuro-blastoma cell line SH-SY5Y and its mechanism.Methods CCK8 assay was used to detect cell activity and deter-mine the optimal dose of DEX and TNF-α.The cells were divided into control group,model group,DEX interven-tion model group,and the intervention group of DEX plus compound C.Western blot was used to detect the expres-sion of p-AMPK,SNHP,KIF5B,Drp1 and OPA1,and ELISA was used to detect the level of IL-1β and IL-6.Mitochondrial membrane potential(Δψm),respiratory chain complex enzyme activity(complex Ⅰ-Ⅳ),ATP,MDA,SOD,GSH,ROS were determined with commercially available kits.Results Compared with control group,level of p-AMPK,OPA1 and SNPH l in model group significantly decreased,while the level of Drp1 and KIF5B significantly increased(P＜0.01).The level of complexⅠ～Ⅳ,Δψm,ATP,GSH and SOD in DEX group signifi-cantly increased as compared with model group.The level of MDA,IL-1β and IL-6 significantly decreased(P＜0.01).Compared with DEX group,the level of Complex Ⅰ-Ⅳ,Δψm,ATP,GSH and SOD in DEX+CC group significantly decreased,while the level of MDA,IL-1β and IL-6 significantly increased(P＜0.01).Conclusions DEX improves mitochondrial function,alleviates oxidative stress and inflammatory response as well as TNF-α-induced cell damage with an AMPK dependent mechanism.

Objective To analyze the causes of changes in the prevalence of respiratory diseases and the reason for changes in medical visit behavior of children in Zhejiang Province during the winter and spring seasons of 2019-2021, and to provide important reference for the allocation of hospital resources, implementation of hierarchical diagnosis and treatment, and epidemic prevention and control. Methods A retrospective study was conducted on 256 937 outpatient medical records from January 23rd to April 23rd of each year from 2019 to 2021 at the Children's Hospital Affiliated to Zhejiang University School of Medicine. Statistical methods were used for data analysis. Results A total of 256 937 cases were selected in the present study, including 157 000 cases in 2019, 22 192 cases in 2020, and 77 745 cases in 2021. The number of patients to the Children's Hospital of Zhejiang University School of Medicine from outside Hangzhou accounted for 41.74%, 14.36% , and 18.53% in 2019-2021, respectively. For 0~2 years old , 3~6 years old , and 7~14 years old groups , the percentages of patients with upper respiratory tract infections were 49.54%, 45.95%, and 46.74%, respectively ; with lower respiratory tract infections were 42.90% , 31.76% , and 22.95% ; with influenza were 2.23% , 3.15% and 4.09%; and with asthma were 1.37%, 5.08%, and 8.15%, respectively. Conclusion From 2019 to 2021, there have been significant changes in the total number of respiratory diseases in children, the proportion of disease types, and the proportion of children's geographical composition. It is necessary to continue to monitor children's respiratory diseases, grasp the dynamic changes in their medical visits in real time, adjust the hospital admission model , implement the graded treatment policy, and promote the prevention and control of respiratory diseases in children.

Objective To explore the correlation between exponential apparent diffusion coefficient(eADC)value before radical hysterectomy and postoperative clinical results in patients with International Federation of Gynecology and Obstetrics(FIGO)stageⅠ/Ⅱ cervical cancer,and to find MR quantitative indicators for predicting the prognosis of patients with early stage cervical cancer.Methods Patients with FIGO stage Ⅰ/Ⅱ cervical cancer who underwent surgical treatment were retrospectively collected.All patients underwent MRI plain scan and diffusion weighted imaging(DWI)scan before surgery.Baseline parameters included age,menopause,stage,tumor size,pathological differentiation and type,lymph node involvement,and postoperative adjuvant therapy.MR parameters included mean apparent diffusion coefficient(ADCmean),normalized apparent diffusion coefficient(nADC),eADC,SIDWI,and SIT2.Baseline and MRI parameters associated with recurrence were determined by Cox regression analysis.Results The progression-free survival(PFS)in the low eADC group was longer than that in the high eADC group(P=0.010).Univariate analysis showed that ADC,nADC and eADC were associated with recurrence(P<0.05).In multivariate analysis,only eADC[hazard ratio(HR)3.610;95%confidence interval(CI)1.467-8.886;P=0.005]was associated with recurrence.Conclusion Preoperative eADC is associated with PFS in patients with surgically treated FIGO stage Ⅰ/Ⅱ cervical cancer and is helpful in evaluating the prognosis of patients with cervical cancer.

[Objective] To compare the clinicopathological characteristics of localized prostate cancers between peripheral zone and transition zone and to evaluate biochemical recurrence-free survival rates between the two groups following radical prostatectomy. [Methods] Between February 2016 and August 2021, prostate cancer candidates meeting the eligibility criteria of the study were retrospectively enrolled and divided into transition zone group and peripheral zone group based on the zonal origin. The patients were followed regularly after radical prostatectomy. Unpaired t-test, χ²-test and Mann-Whitney U-test were used to compare age, serum prostate specific antigen (PSA), tumor volume, Gleason score, laterality of positive biopsy core, mean percentage of positive biopsy cores, clinical/pathological stage, seminal vesicle invasion, lymph node metastasis, and positive surgical margin between the two groups. The biochemical recurrence-free survival rates of the two groups were evaluated by Kaplan-Meier and the differences were determined by log-rank test. [Results] A total of 273 cases were included in the study, among which 176 were peripheral zone cancers and 97 were transition zone cancers. The mean tumor volume of the transition zone group was greater than that of peripheral zone group (P=0.002). The serum PSA of transition zone group was higher than that of the latter (P=0.047); however, both mean percentage of positive biopsy cores and the percentage of seminal vesicle invasion were higher in transition zone group than in peripheral zone group (P=0.028, 0.047). Furthermore, there was no significant difference in biochemical recurrence-free survival rate between the two groups (P=0.783). [Conclusion] Despite the greater tumor volume and higher PSA compared with those in peripheral zone cancers, transition zone cancers have similar biochemical recurrence-free survival rates following radical prostatectomy, suggesting that transition zone cancers may have a lower degree of aggressiveness than the latter.

Objective:To determine the efficacy and influencing factors of thymectomy for bulbar myasthenia gravis.Methods:The clinical data of 120 patients with bulbar myasthenia gravis admitted to the Myasthenia Gravis Comprehensive Diagnosis and Treatment Center of Henan Provincial People's Hospital from March 2018 to June 2023 were collected, with 61 males and 59 females. There were 66 patients with thymoma and 54 patients with non-thymoma. The duration of bulbar muscle involvement before operation ranged from 11 days to 108 months. Preoperative AChR-Ab was positive in 105 cases and negative in 15 cases. There were 28 cases with bulbar muscle involvement as the initial symptom and 92 cases as the non-initial symptom. There were 7 cases with crisis and 113 cases without crisis in the past. The postoperative efficacy was evaluated according to the Myasthenia Gravis post-treatment status evaluation program of the American Myasthenia Gravis Society. Univariate analysis and logistic regression analysis were used to analyze the factors that may affect the surgical efficacy. Results:All 120 patients successfully underwent extended thymectomy, there was no perioperative death. The follow-up time was 3-57 months, with a median of 24 months. Twenty-two patients (18.33%) achieved complete durable remission, 1 patient (0.83%) maintained remission, 65 patients (54.17%) had minimal symptoms, and 20 patients (16.70%) improved. No change in 8 cases (6.67%), no aggravation cases (0), deterioration in 2 cases (1.67%), and death in 2 cases (1.67%). 23 cases(19.17%) achieved clinical remission and 85 cases (70.83%) achieved partial remission. Univariate analysis showed that positive AChR-Ab before operation and duration of bulbar muscle involvement before operation were the influencing factors of surgical efficacy in patients with bulbar MG, and the difference was statistically significant ( P<0.05). Logistic regression analysis showed that positive AChR-Ab before operation and the duration of bulbar muscle involvement before operation were independent influencing factors of surgical efficacy. Conclusion:Thymectomy can effectively relieve the symptoms of bulbar myasthenia gravis. Patients with positive AChR-Ab before surgery and shorter duration of bulbar muscle involvement may benefit more from thymectomy.

Objective Metabolomics was used to analyze the changes of metabolites in the plasma of Fenpropathrin-contaminated rats to find potential biomarkers for forensic identification of Fenpropathrin poisoning.Methods SD rats in the two experimental groups were given 20.5 mg/kg and 41 mg/kg doses of fenpropathrin respectively by gavage.The rats in the control group were given equivalent volume of normal saline.The angular vein blood of rats was collected 24 hours after gavage,and endogenous small molecule metabolites in plasma were investigated by ultra-performance liquid chromatography-time-of-flight mass spectrometry(UPLC-TOF-MS).The data was processed by SIMCA14.1.The differential metabolites in plasma of fenpropathrin-infected rats were screened out according to the Variable Importance in Projection(VIP)and p<0.05 in the OPLS-DA model.Finally,the pathways were analyzed.Results There were significant differences in plasma metabolite levels between the control group and the experimental group,and 17 biomarkers were selected to identify whether the rats had received fenpropathrin,which mainly affected purine metabolism,Alanine,aspartate and glutamate metabolism,arginine biosynthesis,biosynthesis of unsaturated fatty acids and pyrimidine metabolism.Conclusion Fenpropathrin can change the composition of metabolites in rats,and the differential markers screened can provide supportive forensic evidence for cases related to deltamethrin poisoning.