Neurofilament proteins(NFs),defined as a type Ⅳ intermediate filaments,are important components of the neuronal cytoskeleton.They play a key physiological role in maintaining the structural integrity and plasticity of axons and in ensuring the axonal transport function.Under pathological conditions,NFs detach from axons and undergo abnormal aggregation,causing axonal transport dysfunction.In addition,some components of the detached NFs leak into the peripheral circulation system.In patients with amyotrophic lateral sclerosis(ALS),the concentration of NFs is significantly elevated in the cerebrospinal fluid and blood,and the changes in NFs concentration is significantly positively correlated with the disease progression of ALS,suggesting the potential of NFs being used as early diagnostic biomarkers for ALS.In this review,we explored the relationship between NFs structure,assembly,and physiological function,focusing on the molecular mechanisms and clinical manifestations of ALS caused by abnormal assembly of NFs.We comprehensively summarized recent advances in the application of NFs as a new humoral biomarkers for early diagnosis and therapeutic monitoring of ALS.Key challenges in biomarker development—including undefined pathological neurofilament light chain(NFL)fragments,limited antibody availability,and poor assay reproducibility—are discussed.Strategies,including ultrasensitive detection technologies such as single molecule array(Simoa),antibody optimization based on pathological fragment identification,and multi-omics biomarker panels,should be integrated.These approaches may lead to breakthroughs,pave the way for precision-based ALS diagnosis,provide theoretical support for promoting its clinical translation and application,and offer ideas for future research.

Objective To investigate and analyze the occupational stress levels and influencing factors among radiation workers in China, and provide a reference for alleviating occupational stress and promoting mental health. Methods Using the general situation questionnaire, Effort-Reward Imbalance questionnaire, and radiation protection knowledge questionnaire, a convenience sampling method was adopted to investigate the occupational stress of 243 radiation workers in Liaoning, Fujian, Guangdong, and Xinjiang provinces. The independent samples t-test, one-way analysis of variance, chi-square test, and binary logistic regression were used to analyze the influencing factors. Results The average score of Effort-Reward Imbalance was 0.97 ± 0.22, and 100 (41.15%) radiation workers had occupational stress. There were significant differences in the detection rate of occupational stress among radiation workers of different ages, working years in radiation positions, monthly incomes, daily sleep durations, and daily working hours (P < 0.05). Logistic regression analysis identified daily working hours as a factor contributing to occupational stress. Conclusion The occupational stress among radiation workers in China is relatively severe. It is recommended to pay attention to the associated risks and implement targeted intervention measures to reduce the impact of occupational stress.

Objective To analyze the differential expression of non-coding RNAs (ncRNAs) from liver tissues adjacent to hepatic cystic echinococcosis (CE) lesions and distant normal liver tissues using whole transcriptome sequencing, and perform functional annotations of differentially expressed ncRNAs, so as to explore the potential role of ncRNAs in the pathogenesis of CE. Methods Intraoperative liver tissue specimens adjacent to hepatic CE lesions and distant normal liver tissue specimen were sampled from patients with hepatic CE, and the expression profiles of microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs) were detected using whole transcriptome sequencing. Differentially expressed genes were identified, and functional annotations were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In addition, a circRNA/lncRNA-miRNA-messenger RNA (mRNA) competing endogenous RNA (ceRNA) network was constructed using the Cytoscape software, and the expression of hub miRNAs in the network was validated using real-time quantitative reverse transcription PCR (RT-qPCR) assay. Results A total of 41 differentially expressed miRNAs were identified between the adjacent and distal tissues of hepatic CE lesions, including 8 up-regulated and 33 down-regulated miR-NAs, which were significantly enriched in biological processes of Ras signaling and neutrophil activation. Five differentially expressed circRNAs were detected, including 3 up-regulated and 2 down-regulated circRNAs, which were significantly enriched in molecular functions of hormone signaling pathways and RNA transcription regulation. A total of 447 differentially expressed lncRNAs were identified, including 200 up-regulated and 247 down-regulated lncRNAs, which were involved in cell proliferation, immune regulation, and extracellular matrix remodeling pathways. MiRNA target analysis predicted hsa-miR-27a-5p, hsa-miR-21-3p, and hsa-miR-181b-2-3p as hub nodes in the ceRNA network. RT-qPCR assay detected that the relative expression levels of ENSG00000253736, HAS2-AS1, PCSK6, hsa-miR-21-3p, hsa-miR-27a-5p, MIR23AHG, VIPR1-AS1, LINC02910, and hsa-miR-181b-2-3p were 3.00 ± 0.25, 2.75 ± 0.33, 1.01 ± 0.51, 2.65 ± 0.41, 1.01 ± 0.29, 1.10 ± 0.31, 1.05 ± 0.27, 0.25 ± 0.49, and 2.56 ± 0.35 in adjacent tissues of hepatic CE lesions, normalized to that in distant tissues from hepatic CE lesions, respectively (t = 6.21, 5.83, 7.51, 7.46, 6.12, 6.65, 7.13, 1.87 and 7.81, all P values < 0.01), which was consistent with whole transcriptome sequencing results. Conclusions Differentially expressed ncRNAs from adjacent and distal liver tissues of hepatic CE lesions may contribute to the pathological mechanisms of CE through mediating cell proliferation, immune evasion, and inflammatory responses, in which hsa-miR-27a-5p and hsa-miR-21-3p may serve as hub miRNAs.

Gastroesophageal reflux disease (GERD) is a chronic digestive system disorder triggered by multiple factors, which is clinically prevalent and affects patients' quality of life. Laparoscopic fundoplication serves as the mainstay of surgical treatment for GERD, requiring standardized preoperative examinations to assess patients' reflux status and esophageal motility for individualized selection of fundoplication techniques. Intraoperative regulation of the fundoplication tension with a bougie aims to balance the anti-reflux efficacy and the risk of postoperative dysphagia. Additionally, membranous anatomy research guided by embryonic development facilitates optimization of surgical approaches and provides a theoretical basis for surgical innovation. This article deeply discusses the status of GERD diagnosis and treatment, as well as the surgical anti-reflux mechanisms, from multiple aspects including pathogenesis, diagnosis, and surgical management. We also contemplate the existing challenges in the embryonic development and anatomy of the anti-reflux barrier.

Gastroesophageal reflux disease (GERD) is a chronic digestive system disorder triggered by multiple factors, which is clinically prevalent and affects patients' quality of life. Laparoscopic fundoplication serves as the mainstay of surgical treatment for GERD, requiring standardized preoperative examinations to assess patients' reflux status and esophageal motility for individualized selection of fundoplication techniques. Intraoperative regulation of the fundoplication tension with a bougie aims to balance the anti-reflux efficacy and the risk of postoperative dysphagia. Additionally, membranous anatomy research guided by embryonic development facilitates optimization of surgical approaches and provides a theoretical basis for surgical innovation. This article deeply discusses the status of GERD diagnosis and treatment, as well as the surgical anti-reflux mechanisms, from multiple aspects including pathogenesis, diagnosis, and surgical management. We also contemplate the existing challenges in the embryonic development and anatomy of the anti-reflux barrier.

Protease activating receptor (PAR) is a member of G protein-coupled receptor family, which includes four subtypes, namely PAR1, PAR2, PAR3 and PAR4. Except PAR2 trypsin receptor, other subunits belong to thrombin receptor. These receptors exist widely in various tissues of the body, especially in the digestive system to play a certain biological effect. In recent ten years, studies have shown that PAR1 and PAR2 play a key role in immune inflammatory response, which has aroused people′s attention. At present, it is of clinical value to study the development of gastroesophageal reflux disease (GERD) by exploring the unique activation mode of PAR2 in the pathological processes of esophageal mucosal damage, pain transmission, immune inflammatory response, stress and so on. This review aims to elucidate the molecular mechanism of PAR2 in gastroesophageal inflammation.

Obesity is one of the main risk factors for gastroesophageal reflux disease (GERD). With the development of social economy, the global obesity population shows a continuous growth trend, leading to an increase in the incidence rate of GERD. Obesity, especially the central obesity, is closely related to GERD. The increase of intra-abdominal pressure caused by obesity may lead to the destruction of "anti-reflux barrier" through a variety of mechanical mechanisms, and the various cytokines produced by visceral adipose tissue in obesity population may contribute to the occurr-ence and development of GERD through various biological effects. The authors explore the mechanism of obesity in the occurrence and development of GERD from both mechanical and biological effects, aiming to help clinical physicians improve their understanding of GERD.

Objective To evaluate the value of perfusion imaging mismatch and low perfusion ratio(HIR)based on CT perfusion imaging in predicting acute intracranial large vessel occlusion(LVO)associated with intracranial atherosclerotic stenosis(ICAS).Methods A total of 82 pa-tients with acute intracranial LVO who underwent emergency thrombectomy in our hospital from February 2019 to December 2020 were enrolled in this study.According to the etiology,they were divided into ICAS-related LVO group(ICAS-LVO,65 cases)and cardiogenic embolism group(17 cases).ROC curve was plotted to analyze the predictive value of CT perfusion imaging parame-ters.Results Compared with the cardiogenic embolism group,the ICAS-LVO group had signifi-cantly larger male ratio,higher BMI and TG level,more severe progression of disease,longer time from onset to surgery,larger proportion of ischemic penumbra and higher mismatch ratio,and ob-viously less ratio of atrial fibrillation,lower BNP and HDL levels,smaller infarct volume,and lower HIR(P＜0.05,P＜0.01).ROC curve analysis showed that HIR and mismatch ratio had good predictive value for the etiology of ICAS-LVO.The optimal cut-off value of HIR was 0.26,with an AUC value of 0.74,a specificity of 0.88,and a sensitivity of 0.54.The optimal cutoff for the mismatch ratio was 3.84,with an AUC value of 0.84,a specificity of 0.75,and a sensitivity of 0.90.Generalized linear model revealed that HIR and cerebral blood volume index had no signifi-cant difference in prognostic performance(P=0.175).Conclusion HIR and mismatch ratio are helpful to identify the pathogenesis earlier and formulate surgical strategies more accurately,thereby reducing iatrogenic injury to a greater extent,increasing the effective reperfusion rate,re-ducing the disability and mortality,and improving the prognosis of clinical outcomes.

Objective To evaluate the effects of enhanced external counterpulsation (EECP) on exercise capacity and quality of life in patients with chronic heart failure. Methods PubMed, The Cochrane Library, EMbase, CNKI, Wanfang Data, VIP and CBM databases from January 1, 2010 to October 1, 2022 were searched by computer for the randomized controlled trial (RCT) about the intervention of EECP in patients with heart failure. Two researchers independently screened literature and extracted data. The meta-analysis was performed by RevMan 5.3. Results Nineteen RCTs were included. After EECP treatment, 6-minute walk distance (MD=57.37, 95%CI 40.89 to 70.85, P<0.001) and left ventricular ejection fraction improved (SMD=0.85, 95%CI 0.55 to 1.14, P<0.001). B-type natriuretic peptide decreased significantly (SMD=−0.67, 95%CI −1.09 to −0.25, P=0.002). The left ventricular end diastolic diameter (MD=−7.77, 95%CI −11.49 to −4.04, P<0.001), and the left ventricular end systolic diameter were significantly reduced (MD=−8.53, 95%CI −13.47 to −3.60, P<0.001). The quality of life of patients was improved (MD=16.34, 95%CI 0.59 to 32.10, P=0.04). Conclusion EECP can improve the exercise ability and the quality of life in patients with heart failure. However, more and larger well-designed RCTs are still needed to verify this conclusion.

BACKGROUND:The proximal femoral nail antirotation is the preferred treatment for reverse osteoporotic intertrochanteric fractures.Bone cement enhancement can reduce the probability of proximal femoral nail antirotation cut-out and cut-through,but there are no relevant biomechanical studies demonstrating the effect of bone cement content and location on the stress and displacement of the fracture end. OBJECTIVE:To investigate the effects of different contents and locations of bone cement in cement-reinforced proximal femoral nail antirotation on stress,strain,and displacement of reverse osteoporotic femoral intertrochanteric fractures in the elderly by finite element analysis. METHODS:A healthy adult female right femur model was extracted by Mimics software and smoothed in Geometric software.Five types of internal fixation methods of proximal femoral nail antirotation(cementless,cephalic spherical 1 mL,cephalic spherical 2 mL,cephalic spherical 3.4 mL,and cylindrical 5 mL around spiral blade)and femoral intertrochanteric fracture(AO subtype 31-A3.1 type)model were established in Solidworks software.After assembly,the total stress distribution,peak stress and displacement of the five models of implants with the femur were compared in Ansys software. RESULTS AND CONCLUSION:(1)The peak stresses of proximal femoral nail antirotation with head-end spherical 1 mL,head-end spherical 2 mL,head-end spherical 3.4 mL,and cylindrical 5 mL enhanced proximal femoral nail antirotation around the spiral blade respectively were 571.07 MPa(located at the junction of the spiral blade and the main nail),495.45 MPa(located at the junction of the spiral blade and the main nail),467.20 MPa(located at the junction of the main nail and the distal screw connection),642.70 MPa(located at the junction of the main nail and distal screw connection),and 458.58 MPa(located at the junction of the spiral blade and the main nail).(2)The maximum displacements of proximal femoral nail antirotation with head end sphere 1 mL,head end sphere 2 mL,head end sphere 3.4 mL,and with cylindrical 5 mL enhancement around the spiral blade were 9.260 5,7.589 1,7.316 8,6.790 7,and 6.615 7 mm,respectively,all of which were located at the proximal end of the femoral head.(3)These findings revealed that for reverse femoral intertrochanteric fractures treated with proximal femoral nail antirotation,the bone cement enhancement had significant mechanical stability compared with no enhancement,and the enhancement of the spiral blade 5 mL around the perimeter was the best,which is more preferable for aged unstable intertrochanteric fractures.