AIM:This study was performed to investigate the impact of neutrophil extracellular traps(NETs)on scar formation following urethral trauma.METHODS:(1)Clinical samples were derived from patients of Department of Urology,The First Affiliated Hospital of Fujian Medical University,from June 2021 to December 2022.Levels of NETs in the blood and urine were compared between patients with urethral trauma(n=20)and those without urethral trauma(controls,n=20).The relationship between NETs and scar formation was analyzed.(2)Urethral fibroblasts were isolated from urethral scar tissues,and neutrophils were induced to produce NETs in vitro.The urethral fibroblasts were treated with normal saline,0.5 mg/L NETs,or 1.5 mg/L NETs to investigate the effects of NETs on activation and collagen syn-thesis of urethral fibroblasts.Additionally,a rabbit model of urethral trauma was established and the animals were dioided into four groups to explore the therapeutic potential of deoxyribonuclease I(DNase I)in preventing urethral scar forma-tion:control,operation + transforming growth factor-β1(TGF-β1),operation + normal saline,and operation+DNase I.RESULTS:The level of NETs in urine increased after urethral trauma(P<0.05),but the level of NETs in blood did not change(P>0.05).In the animal models,the urethral scar became more severe as the level of NETs in the urine increased(P<0.05).At the cellular level,NETs promoted the viability,migration,and collagen synthesis of urethral fibroblasts(P<0.05)..Additionally,urethral injection of DNase I after trauma reduced the level of NETs and inhibited the formation of urethral scar tissue in the animal models(P<0.05).CONCLUSION:Infiltration of NETs promotes activation of urethral fibroblasts and scar formation after urethral trauma.

Background In recent years, a growing number of studies have indicated that perfluorooctanoic acid (PFOA) exposure can impact heart development, though the specific mechanisms remain elusive. The aryl hydrocarbon receptor (AHR) is a critical environmental sensor capable of inducing oxidative stress and cell apoptosis. Objective To explore the role of AHR in the cardiac developmental toxicity of PFOA by using zebrafish embryo as an in vivo model. Methods Zebrafish embryos at 2 h post-fertilization (2 hpf) were exposed to dimethyl sulfoxide (DMSO) control, 1, 10, 100, and 1000 μg·L⁻¹ of PFOA. The AHR inhibitor CH223191 (CH) was added to the high-concentration group (1000 μg·L⁻¹) to form an intervention group. Under a dissecting microscope, the survival rate, mortality rate, heart rate, and heart malformation rate of 72 hpf zebrafish larvae were assessed. The activity of AHR was measured using 7-ethoxyresorufin-O-dealkylation (EROD) staining. The levels of intracellular and mitochondrial ROS in the heart of zebrafish larvae were assessed using dichloro-dihydro-fluorescein diacetate and MitoSOX™ Red, respectively. Apoptosis was examined using acridine orange (AO) staining and Immunofluorescence method. Total RNA was extracted from dissected hearts, and mRNA expression levels of oxidative stress-related genes (sod2, cat) and apoptosis-related gene (p53) were analyzed using quantitative PCR. Results Compared to the DMSO control group, PFOA at even the lowest concentration (1 μg·L⁻¹) increased heart malformation rate (P＜0.05) and reduced heart rate (P＜0.01) in the zebrafish larvae at 72 hpf, and the results showed a clear concentration-response relationship. Adding the AHR inhibitor CH significantly decreased heart malformation rate and restored heart rate to the control group level. The EROD results showed that PFOA at 1000 μg·L⁻¹ increased AHR activity (P＜0.001). Further studies revealed that PFOA caused a dose-dependent increase in intracellular ROS (P<0.001) and an increase in mitochondrial ROS (P<0.001) in the heart region of zebrafish larvae. A high dose of PFOA (1000 μg·L⁻¹) also induced elevated mRNA expression levels of oxidative stress-related genes sod2 and cat (P<0.05). Addition of the AHR inhibitor CH effectively antagonized PFOA-induced (1000 μg·L⁻¹) oxidative stress in the heart of zebrafish larvae (P<0.001). In addition, PFOA exposure induced a concentration-dependent increase in apoptotic bodies in the heart of zebrafish larvae (P<0.05). Moreover, PFOA at 1000 μg·L⁻¹ caused an increase in the cleaved-caspase 3 immunofluorescence signal (P<0.05) as well as overexpression of the apoptosis-associated gene p53 (P<0.001).which were attenuated by the CH supplementation. Conclusion PFOA triggers oxidative stress and apoptosis via AHR activation in the heart of zebrafish larvae, resulting in cardiac defects.

Objective:To construct a prognostic nomogram based on epithelial-stromal interaction protein 1(EPSTI1)and predict the pro-gnosis of clear cell renal cell carcinoma(ccRCC).Methods:A retrospective analysis was performed from January 2012 to December 2015 at The First Affiliated Hospital of Fujian Medical University,on 221 patients with ccRCC who underwent surgical treatment in our center and 533 patients with ccRCC in The Cancer Genome Atlas(TCGA)database.Immunohistochemical(IHC)staining was performed on adjacent nor-mal and cancerous tissues to analyze the expression level of EPSTI1 and its correlation with clinicopathological characteristics.Kaplan-Meier survival analysis was performed for the overall survival(OS)and disease-free survival(DFS)of patients with high and low EPSTI1 expression levels.Univariate and multivariate Cox proportional hazards models were used to analyze the prognostic factors for OS,and a nomogram model was constructed and verified.Results:The IHC scores and mRNA expression levels of EPSTI1 were significantly higher in ccRCC tissues than in normal tissues(all P<0.001).EPSTI1 was expressed at higher levels in cancer tissues at higher T stages(P=0.036,P=0.006).The EPSTI1 protein expression level was related to the maximum tumor diameter and TNM stage(P=0.002,P=0.032,respectively).The OS and DFS were higher in the low-EPSTI1-expression group than the high-EPSTI1-expression group(P=0.046,P=0.003,P=0.001).Univariate and multivariate Cox regression analyses showed that a high EPSTI1 protein expression level,WHO/ISUP grade,and AJCC/TNM stage were independent risk factors for poor prognosis(P=0.009,P=0.039,P<0.001).The prognostic nomogram model constructed based on the above variables was su-perior to the AJCC/TNM stage in predicting the 5-year OS,and the calibration curve showed that the predicted value of the model was con-sistent with the actual value.Conclusions:The nomographic model based on EPSTI1,AJCC/TNM staging and WHO/ISUP staging has a strong predictive ability for the prognosis of renal clear cell carcinoma.

Objective:To evaluate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of myelofibrosis (MF).Methods:In this case series, the clinical data of 18 patients with MF who received allo-HSCT in the Department of Hematology, Peking University People′s Hospital from December 2008 to December 2023 were retrospectively studied. Kaplan-Meier survival analysis and competitive risk model were used to evaluate the probabilities of 3-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplant related mortality (TRM). The transplant related complications were also analyzed.Results:Among the 18 patients included, there were 12 males and 6 females, with a median age of 50 (range: 28-64) years. All 18 patients achieved neutrophil engraftment, and the time of neutrophil engraftment [ M ( Q1, Q3)] was 16.0 (11.8, 18.0) days. Twelve patients achieved platelet engraftment, and the platelet engraftment time was 21.0 (16.2, 43.2) days. Six patients had grade Ⅱ to Ⅳ acute graft-versus-host disease (GVHD), and six patients had chronic GVHD. The 3-year OS rate and DFS rate after transplantation were 62.2% and 52.2%, respectively. The 3-year CIR and TRM were 29.7% and 24.6%, respectively. Four patients died during follow-up, with the main cause of death being infections. Conclusion:Matched sibling allo-HSCT is a feasible option for the treatment of MF.

Epilepsy is one of common diseases of nervous system,which is mainly manifested as repeat-ed abnormal neuronal discharges in the brain.If it cannot be effectively controlled,it can cause irreversible neuronal damage in the brain.Non-coding RNAs plays an important role in the development and progression process of epilepsy and are involved in regulating autophagy,apoptosis,neuroinflammation,synaptic remode-ling and other physiological and pathological processes,especially in the regulation of autophagy in epileptic neuronal cells.This article reviews the regulatory relationship between microRNA and long non-coding RNAs,circRNAs in non-coding RNAs with autophagy in the occurrence and development of epilepsy to pro-vide a direction for the precise treatment and prevention of epilepsy.

The core competencies of Operating Room specialist nurses are the key to being competent in Operating Room nursing work. However, the core competencies that Operating Room specialist nurses should possess in China are not yet clear, and there is no unified and standardized training model. This paper summarizes the concepts, core competency standards, and training models of Operating Room specialist nurses, explores the existing problems in admission conditions, curriculum arrangement, training content, training methods, and assessment of Operating Room specialist nurses, and puts forward suggestions for the training of Operating Room specialist nurses in China, in order to promote the improvement of core competency of Operating Room specialist nurses and the homogenization and standardization of training models.

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

There are over 6000 rare diseases in the world, affecting more than 300 million people. Early and precise diagnosis of rare diseases has always been the goal in clinical medicine. Emerging computer vision technology now greatly enhance medicine and healthcare and shows the potential in assisting the diagnosis and treatment for rare diseases. The technology can be a useful tool for extracting disease-relevant patterns from medical imaging. However, the effectiveness of its application depends on the complexity of the medical cases. In this paper, we summarize the challenges and emerging solution for the application of computer vision in diagnosis, rehabilitation as well as management of rare musculoskeletal diseases.

In the last decade, it has become increasingly recognized that a balanced gut microbiota plays an important role in maintaining the health of the host. Numerous clinical and preclinical studies have shown that changes in gut microbiota composition are associated with a variety of neurological diseases, e.g., Parkinson's disease, Alzheimer's disease, and myasthenia gravis. However, the underlying molecular mechanisms are complex and remain unclear. Behavioral phenotypes can be transmitted from humans to animals through gut microbiota transplantation, indicating that the gut microbiota may be an important regulator of neurological diseases. However, further research is required to determine whether animal-based findings can be extended to humans and to elucidate the relevant potential mechanisms by which the gut microbiota regulates neurological diseases. Such investigations may aid in the development of new microbiota-based strategies for diagnosis and treatment and improve the clinical management of neurological disorders. In this review, we describe the dysbiosis of gut microbiota and the corresponding mechanisms in common neurological diseases, and discuss the potential roles that the intestinal microbiome may play in the diagnosis and treatment of neurological disorders.
Animals ; Humans ; Gastrointestinal Microbiome/physiology* ; Nervous System Diseases ; Parkinson Disease ; Microbiota ; Brain

OBJECTIVE: To explore the clinical feature and genetic variant of a child with autosomal recessive Charlevoix-Saguenay type spastic ataxia (ARSACS). METHODS: Clinical data of a child who was admitted to the West China Second Hospital of Sichuan University on April 30, 2021 was collected. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The child, a 3-year-and-3-month-old female, had a complain of "walking instability for over a year". Physical and laboratory examination revealed progressive and aggravated gait instability, increased muscle tone of the right limbs, peripheral neuropathy of the lower limbs, and thickening of retinal nerve fiber layer. The results of WES revealed that she has harbored a maternally derived heterozygous deletion of exons 1 to 10 of the SACS gene, in addition with a de novo heterozygous c.3328dupA variant in exon 10 of the SACS gene. Based on the ACMG guidelines, the exons 1-10 deletion was rated as likely pathogenic (PVS1+PM2_Supporting), and the c.3328dupA was rated as a pathogenic variant (PVS1_Strong+PS2+PM2_Supporting). Neither variant was recorded in the human population databases. CONCLUSION The c.3328dupA variant and the deletion of exons 1-10 of the SACS gene probably underlay the ARSACS in this patient.
Female ; Humans ; Heat-Shock Proteins/genetics* ; Muscle Spasticity/genetics* ; Mutation ; Spinocerebellar Ataxias/pathology* ; Child, Preschool