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.

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 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 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 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.

Objective To investigate the expression significance and prognostic value of long non-coding RNA tumor susceptibility candidate gene 9(lncRNA CASC9)and YKT6 in oral squamous cell carcinoma(OSCC).Methods A total of 110 patients with OSCC treated in the Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine from January 2016 to January 2018 were selected as the study objects.The mRNA expression of lncRNA CASC9 and YKT6 in OSCC cancer tissue and adjacent tissues was detected by real-time fluorescence quantitative PCR.Immunohistochemistry was used to detect YKT6 protein expression in OSCC cancer tissue and adjacent tissues.Kaplan-Meier curves were used to analyze the influence of different lncRNA CASC9 and YKT6 mRNA expression on the prognosis of OSCC patients.Cox regression model was used to analyze the prognostic factors of OSCC.Results The lncRNA CASC9 and YKT6 mRNA expression in OSCC cancer tissues were 3.12±0.57 and 2.69±0.42,respectively,which were significantly higher than those in adjacent tissues(1.02±0.25,1.13±0.21),and the differences were statistically significant(t=35.386,34.843,P＜0.05).The positive rate of YKT6 protein in OSCC cancer tissues was 81.82％(90/110),which was higher than that in adjacent tissues[9.09％(10/110)],and the difference was statistically signifi-cant(x2=117.333,P＜0.05).There was a positive correlation between lncRNA CASC9 mRNA expression and YKT6 mRNA expression in OSCC cancer tissues(r=0.788,P＜0.001).The lncRNA CASC9 and YKT6 mRNA expressions in cancer tissues of OSCC with TNM stages m to Ⅳ,low differentiation and lymph node metastasis were higher than those in cancer tissues of OSCC with TNM stages Ⅰ to Ⅱ,high school differenti-ation and no lymph node metastasis,the difference was statistically significant(all P＜0.05).The 5-year cu-mulative survival rate of lncRNA CASC9 high expression group and YKT6 mRNA high expression group was lower than that of lncRNA CASC9 low expression group and YKT6 mRNA low expression group,and the difference was statistically significant(Log-rank X2=7.080,8.741,P=0.008,0.003).High expression of ln-cRNA CASC9,high expression of YKT6 mRNA,TNM stage m to Ⅳ,low differentiation and lymph node me-tastasis were prognostic risk factors in OSCC patients.Conclusion The expression of lncRNA CASC9 and YKT6 in OSCC cancer tissue is elevated,which can be used as tumor markers to evaluate the prognosis of OS-CC patients.

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85％of all cancer cases in the country.Several guidelines have been used to diagnose and treat liver cancer.However,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual patients.Therefore,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi method.The classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were developed.These recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment prognosis.The findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.

Objective:Acoustic neuroma(AN)is a benign tumor that usually affects a patient's hearing and balance function.For the screening and diagnosis of AN,the traditional approach mainly relies on audiological examination and magnetic resonance imaging(MRI),often ignoring the importance of vestibular function assessment in the affected area.As an emerging method of vestibular function detection,video head impulse test(vHIT)has been widely used in clinic,but research on its use in AN diagnosis is relatively limited.This study aims to explore the value of vHIT in the diagnosis of AN,vestibular dysfunction assessment,and postoperative compensation establishment in unilateral AN patients undergoing unilateral AN resection through labyrinthine approach. Methods:This retrospective study was conducted on 27 AN patients who underwent unilateral AN resection via labyrinthine approach from October 2020 to March 2022 in the Department of Otolaryngology-Head and Neck Surgery,the Second Xiangya Hospital,Central South University.vHIT was performed 1 week before surgery to assess vestibular function,pure tone audiometry(PTA)was used to assess hearing level,and ear MRI was used to assess tumor size.Follow-up vHIT was conducted at 1 week,1 month,6 months,and 1 year post-surgery.The correlation of vHIT with hearing and tumor size was analyzed. Results:Preoperative vHIT showed that the posterior semicircular canal on the affected side was the most common semicircular canal with reduced vestibulo-ocular reflex(VOR)gain.There was a correlation between the VOR gain of vHIT on the affected side and the hearing level(r=-0.47,P<0.05)or tumor size(r=-0.54,P<0.01).The results of vHIT on the affected side showed that the hearing level and mean VOR gain of the anterior semicircular canal increased slightly with time,and the amplitude and saccade percentage of the dominant saccades of the 3 semicircular canals increased,while the latency time decreased,with the most obvious changes occurring 1 week post-surgery. Conclusion:vHIT can effectively monitor the changes of vestibular function in AN patients before and after surgery and has application value in assisting the diagnosis of vestibular dysfunction in AN patients.

Objective:Ménière's disease(MD)is an idiopathic inner ear disorder characterized by recurrent episodes of episodic rotational vertigo,fluctuating hearing loss,tinnitus,and a feeling of ear stuffiness.Endolymphatic sac(ES)-related surgery is used primarily in patients with MD who have failed to respond to pharmacologic therapy.Endolymphatic duct blockage(EDB)is a new procedure for the treatment of MD,and related clinical studies are still scarce.This study aims to investigate the dynamic changes in endolymphatic hydrops(EH)and the long-term surgical outcomes in MD patients undergoing EDB,and to evaluate the impact of different types of ES on the surgical efficacy. Methods:A retrospective analysis was conducted on 33 patients with refractory MD who underwent EDB.Based on the morphology of their endolymphatic sacs,patients were divided into a normal-type group(n=14)and an atrophic-type group(n=19).The frequency of vertigo symptoms,hearing,vestibular function,and the dynamic changes of gadolinium-enhanced MRI of the inner ear were compared were compared before and after surgery between the 2 groups. Results:Compared with the atrophic-type group,the patients in the normal-type group had a higher rate of complete vertigo control,better cochlear and vestibular function,and a lower endolymph to vestibule volume ratio(all P<0.05).In addition,7 patients in the normal-type group were found to have reversal of EH,while no reversal of EH was detected in the atrophic-type group after surgery. Conclusion:The response to EDB treatment varies between normal and atrophic MD patients,suggesting that the 2 pathological types of endolymphatic sacs may have different underlying mechanisms of disease.