Objective:To retrospectively analyze the clinical features and surgical efficacy of congenital cholesteatoma （CC） and acquired cholesteatoma （AC） in children. Methods:Clinical data of 169 children with middle ear cholesteatoma were reviewed in the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University from January 2010 to July 2020. The clinical characteristics, stages, surgical methods, and postoperative recurrence rates were analyzed and summarized. Results:The age distribution of enrolled children ranged from 2 to 14 years. The mean age of the CC group was （5.60±2.48） years compared with （6.45±2.48） years in the AC group, and the difference was statistically significant （P<0.05）. Preoperative hearing in the CC group was （40.06±13.52） dB HL, which was better than in the AC group at （48.40±13.84） dB HL （P<0.05）. The proportion of stage Ⅰ in the CC group was lower than that in the AC group according to EAONO/JOS staging （P<0.05）. The recurrence rate after primary surgery was 19.23% （10/52） in the CC group compared with 36.29% （45/124） in the AC group （P<0.05）. The mastoid retention rates after all operations were 28.85% （15/52） in the CC group and 5.65% （7/124） in the AC group （P<0.05）. Conclusion:Compared with congenital cholesteatoma, acquired cholesteatoma in children is more aggressive and has more complications, higher postoperative recurrence rate, and less possibility of mastoid retention. Early clinical detection and treatment are required, and canal wall-down tympanoplasty should be considered in surgery.
Humans ; Cholesteatoma, Middle Ear/congenital* ; Child ; Retrospective Studies ; Child, Preschool ; Adolescent ; Male ; Female ; Recurrence ; Cholesteatoma/congenital* ; Tympanoplasty ; Treatment Outcome

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

OBJECTIVE To establish a clinical pharmaceutical pathway of anti-infective therapy for high-risk populations of antibiotic-associated encephalopathy （AAE）， and analyze its application effects. METHODS Clinical pharmacists developed the “AAE High-Risk Population Screening Form” and “Antibiotic AAE Risk Comparison Form” based on literature and expert opinions， and established the “Clinical Pharmaceutical Pathway of Anti-infective Treatment for AAE High-Risk Population” in our hospital. A prospective， non-randomized controlled study was conducted from May 2023 to April 2024， including 50 cases in the observation group and 50 cases in the control group among patients with pulmonary infections admitted to the Dept. of Internal Medicine in our hospital. The observation group was involved in the development of an anti-infective treatment following the clinical pharmaceutical pathway by clinical pharmacists， while the control group received routine anti-infective treatment by clinical physicians. The occurrence of AAE， the rational antibiotic drug use， and the effectiveness of initial anti-infective treatment in the two groups were observed， and the intervention measures and outcomes of AAE cases were summarized. RESULTS The anti-infective treatment clinical pharmaceutical pathway for AAE high-risk population was preliminarily established in our hospital. The analysis of the application effects showed that there was 1 case of AAE in the observation group and 8 cases in the control group， with a significantly lower incidence of AAE in the observation group than in the control group； the rational antibiotic drug use and the effectiveness of initial anti-infective treatment in the observation group were both significantly superior to those in the control group （P＜0.05）. Drug withdrawal and dressing change were the preferred effective intervention measures for AAE， and encephalopathy treatment drugs could be used as auxiliary measures for symptom relief. Timely and effective intervention was conducive to rapid symptom relief， with a total improvement rate of AAE of 88.89%. CONCLUSIONS The anti-infective treatment clinical pharmaceutical pathway for AAE high-risk population can effectively prevent the occurrence of AAE as well as contribute to promoting rational drug use and the effectiveness of initial anti-infection plans and strengthening treatment outcomes.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

BACKGROUND:Pain mechanisms in patients with lumbar disc herniation are associated with inflammation,autophagy is closely related to intervertebral disc diseases and inflammatory response,and aberrant miR-206 expression can trigger skeletal diseases. OBJECTIVE:To investigate the mechanism of miR-206 on inflammation,analgesia and autophagy related proteins in nucleus pulposus in rats with lumbar disc herniation. METHODS:Sixty SPF male Sprague-Dawley rats were randomly divided into control group,model group,miR-206 mimics-NC group,miR-206 mimics group,miR-206 inhibitor-NC group and miR-206 inhibitor group.Animal models of lumbar disc herniation were established except for the control group.Ten days after modeling,miR-206 mimics-NC group,miR-206 mimics group,miR-206 inhibitor-NC group and miR-206 inhibitor group were injected with miR-206 mimics-NC(20 μmol/L,10 μL),miR-206 mimics(20 μmol/L,10 μL),miR-206 inhibitor-NC(20 μmol/L,10 μL)and miR-206 inhibitor(20 μmol/L,10 μL),respectively.Administration was given once a day for 4 continuous days.The control group and model group were injected with the same dose of normal saline.The paw withdrawal mechanical threshold of bilateral hind feet was measured by Von Frey filaments,and the paw withdrawal thermal latency of bilateral hind feet was measured by heat pain tester.The morphology of dorsal root ganglia was observed by hematoxylin-eosin staining.The expressions of inflammatory factors phospholipase A2,cyclooxygenase 2,prostaglandin E2,tumor necrosis factor α,and interleukin 1β in nucleus pulposus were detected by qPCR.The expressions of autophagy-related proteins LC3I and Beclin-1 were detected by western blot assay. RESULTS AND CONCLUSION:At 3,7,and 14 days after modeling,the paw withdrawal mechanical threshold and paw withdrawal thermal latency were both decreased in the model group compared with the control group,while the levels of phospholipase A2,cyclooxygenase 2,prostaglandin E2,tumor necrosis factor α,interleukin 1β,LC3I and Beclin-1 increased(P<0.05).The above indexes showed no significant changes in the miR-206 inhibitor-NC group and miR-206 mimics-NC group compared with the model group(P>0.05).Compared with the miR-206 mimics-NC group,the miR-206 mimics group had lower paw withdrawal mechanical threshold and paw withdrawal thermal latency and higher levels of phospholipase A2,cyclooxygenase 2,prostaglandin E2,tumor necrosis factor α,interleukin 1β,LC3I,and Beclin-1 levels(P<0.05).Compared with the miR-206 inhibitor-NC group,the rats in the miR-206 inhibitor group showed opposite changes in the above indicators,and there were significant differences between the two groups(P<0.05).To conclude,inhibition of miR-206 can significantly improve the level of inflammatory factors in nucleus pulposus of rats with lumbar disc herniation,increase pain threshold,and reduce autophagy.The mechanism is related to the inhibition of LC3I and Beclin-1 expression.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective To investigate the effect of long non-coding RNA(lncRNA)macrophage migration inhibitory factor antisense RNA1(MIF-AS1)on the malignant biological behavior of prostate cancer(PC)cells by regulating the miR-423-5p/pyrroline-5-carboxylic acid reductase 1(PYCR1)axis.Methods PC3 cells were cultured in vitro to knock down the expression of MIF-AS1 or down-regulate the expression of miR-423-5p.The expression of MIF-AS1,miR-423-5p and PYCR1 mRNA in tumor tissues and adjacent tissues and cells of PC patients were detected.The cell proliferation,apoptosis,migration,and invasion were detected and the expression of PYCR1 protein was detected by Western blot.The relationships between miR-423-5p,IF-AS1 and PYCR1 were verified.Results The MIF-AS1 and PYCR1 mRNA were observed to be highly expressed in the tumor tissues,while miR-423-5p was lowly expressed.Silenced MIF-AS1 inhibited the proliferation,migration and invasion of PC3 cells and up-regulated miR-423-5p induced cell apoptosis(P＜0.05).Inhibition of miR-423-5p expression reversed the inhibitory effect of silencing MIF-AS1 on malignant behavior of PC3 cells(P＜0.05).miR-423-5p was correlated with MIF-AS1 and PYCR1 by targeted regulation.Conclusion Silencing MIF-AS1 may inhibit the expression of PYCR1 by up-regulating miR-423-5p,thereby inhibiting the malignant behavior of PC cells.

Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

Objective:To explore the prevalence and independent associated factors of vascular calcification (VC) in non-dialysis chronic kidney disease (CKD) patients of stage 3-5.Methods:It was a single-center cross-sectional observational study. Non-dialysis stage 3-5 CKD patients ≥18 years old who were admitted to the Department of Nephrology, the First Affiliated Hospital of Sun Yat-sen University from May 1, 2022 to December 31, 2022 with VC evaluation were enrolled. The patients' general information, laboratory examination and imaging data were collected. Coronary artery calcification (CAC), thoracic aorta calcification (TAC), abdominal aorta calcification (AAC), carotid artery calcification and aortic valve calcification (AVC) were evaluated by cardiac-gated electron-beam CT (EBCT) scans, lateral lumbar x-ray, cervical macrovascular ultrasound and echocardiography, respectively. The differences in clinical data and the prevalence of VC at different sites of patients with different CKD stages were compared, and the prevalence of VC at different sites of patients in different age groups [youth group (18-44 years old), middle-aged group (45-64 years old) and elderly group (≥65 years old)] and patients with or without diabetes were compared. Multivariate logistic regression analysis was used to analyse the independent associated factors of VC for different areas.Results:A total of 206 patients aged (51±14) years were included, including 129 (62.6%) males. There were 44 patients with CKD stage 3 (21.4%), 51 patients with CKD stage 4 (24.8%), and 111 patients with CKD stage 5 (53.9%). CKD was caused by chronic glomerulonephritis [104 cases (50.5%)], diabetic kidney damage [35 cases (17.0%)], hypertensive kidney damage [29 cases (14.1%)] and others [38 cases (18.4%)]. Among 206 patients, 131 (63.6%) exhibited cardiovascular calcification, and the prevalence of CAC, TAC, AAC, carotid artery calcification, and AVC was 37.9%, 43.7%, 37.9%, 35.9% and 9.7%, respectively. The overall prevalence of VC in young, middle-aged and elderly patients was 24.6%, 73.6% and 97.4%, respectively. With the increase of age, the prevalence of VC in each site gradually increased, and the increasing trend was statistically significant (all P<0.001). The overall prevalence of VC in CKD patients with diabetes was 92.5% (62/67), and the prevalence of VC at each site in the patients with diabetes was significantly higher than that in the patients without diabetes (all P<0.001). Multivariate logistic regression analysis revealed that age (every 10 years increase, OR=2.51, 95% CI 1.77-3.56, P<0.001), hypertension ( OR=5.88, 95% CI 1.57-22.10, P=0.009), and diabetes ( OR=4.66, 95% CI 2.10-10.35, P<0.001) were independently correlated with CAC; Age (every 10 years increase, OR=6.43, 95% CI 3.64-11.36, P<0.001) and hypertension ( OR=6.09, 95% CI 1.33-27.84, P=0.020) were independently correlated with TAC; Female ( OR=0.23, 95% CI 0.07-0.72, P=0.011), age (every 10 years increase, OR=3.90, 95% CI 2.42-6.29, P<0.001), diabetes ( OR=5.37, 95% CI 2.19-13.19, P<0.001) and serum magnesium ( OR=0.01,95% CI 0-0.35, P=0.014) were independently correlated with AAC. Moreover, age and diabetes were independently correlated with carotid artery calcification, AVC and overall VC Conclusions:The prevalence of VC in non-dialysis CKD patients of stage 3-5 is 63.59%, of which CAC reaches 37.9%, TAC is the most common one (43.7%), while AVC is the least one (9.7%). Age and diabetes are the independent associated factors for VC of all sites except TAC, while hypertension is an independent associated factor for both CAC and TAC.

Objective To carry out a proficiency testing of content determination of geniposide in Gardeniae fructus,evaluate the content determination ability of index components in traditional Chinese medicine in the laboratory of inspection and detection in drug-related fields,and improve the quality control ability of content determination of related laboratories.Methods The laboratory's capability-verification activities were conducted based on the CNAS-RL02 Rules for Proficiency Testing and ISO/IEC 17043 Conformity Assessment-General Requirements for Proficiency Testing.After preparing the sample,the results of homogeneity and stability tests were analyzed according to CNAS-GL003 Guidance on Evaluating the Homogeneity and Stability of Samples Used for Proficiency Testing.After the test results were qualified,they were used as proficiency testing samples and randomly distributed to participants.The results were collected,and the robust statistical method and the Z scores were used to analyze the results of these laboratories'reports.Results 403 laboratories in this proficiency testing program reported the results,of which 367 results were acceptable,accounting for 91.07％,17(4.22％)laboratories obtained suspicious results,and 19 laboratories gave unsatisfactory results,with the dissatisfaction rate of 4.71％.Conclusion The majority of the 403 participant laboratories have the ability to determine the content of geniposide in Gardeniae fructus by HPLC and the laboratory testing ability and quality management level of the drug monitoring system are high.This proficiency testing provides a basis for understanding the technical reserve capacity and management level of China's pharmaceutical inspection and testing laboratories,and provides technical support for future government supervision.