The doublecortin (DCX) gene encodes DCX, a microtubule-associated protein that plays a crucial role in brain development. DCX variants can disrupt microtubule binding and stabilization, interfere with intracellular transport, and affect post-translational modifications. A correlation exists between variant types and clinical severity. Animal models and induced pluripotent stem cell (iPSC) models simulating DCX deficiency revealed the dynamic progression of the disease, which has provided a powerful tool for investigating disease mechanisms and screening therapeutic agents. Currently there is no cure for DCX variants, with treatment primarily relying on anti-epileptic drugs and symptom management. Basic research is now offering new avenues for future therapeutic approaches. This article has summarized the potential pathogenic mechanisms and therapeutic strategies for the DCX variants, with an aim to provide insights for clinical treatment.
Humans ; Doublecortin Protein ; Doublecortin Domain Proteins ; Animals ; Neuropeptides/metabolism* ; Microtubule-Associated Proteins/metabolism* ; Mutation

Background: The hypotension prediction index (HPI) is an algorithm designed to predict hypotension. Some studies have reported that HPI-guided hemodynamic management strategies decrease intraoperative hypotension and complications; however, the effect of HPI on reducing perioperative complications is controversial. This meta-analysis aimed to assess the efficacy of the HPI in reducing major complications and intraoperative hypotension. Methods: We conducted this meta-analysis according to the PRISMA statement and Cochrane Handbook guidelines. A comprehensive literature review was conducted to identify studies focusing on the efficacy of HPI-guided management in reducing intraoperative hypotension and postoperative complications. The PubMed, Embase, Scopus, and Web of Science databases were searched, and the resulting data were combined to calculate the pooled mean differences or risk ratios (RRs) with 95% CIs of both randomized controlled trials (RCTs) and retrospective studies, as appropriate. Heterogeneity and potential publication bias were also assessed. Results: Nineteen articles (12 RCTs and 7 retrospective studies) with 2570 recruited patients were included in this meta-analysis. The critical evaluation of the study quality revealed a low risk of bias in the included RCTs. Among the non-randomized trials, one was rated 7, two were rated 8, and the remaining four were rated 9 on the Newcastle-Ottawa Scale, indicating high quality and a low risk of bias. HPI-guided management significantly reduced intraoperative hypotension and associated major complications (RR = 0.79, 95% CI [0.69–0.90], I2 = 0, P < 0.001). Blood loss and length of hospital stay were comparable between the groups. Conclusions HPI-guided management significantly reduced intraoperative hypotension and major complications.

Bruch's membrane opening(BMO)is the true anatomical border of the optic nerve head and provides higher anatomical accuracy, structural stability and measurement repeatability than traditional assessments based on the clinically visible optic disc margin. Optical coherence tomography(OCT)serves as a key technical tool for quantitative assessment of BMO-associated structural parameters. With the development of spectral-domain OCT(SD-OCT)and swept-source OCT(SS-OCT), parameters such as BMO-minimum rim width(BMO-MRW), BMO-minimum rim area(BMO-MRA), BMO area, offset, tilt, and torsion have emerged as important imaging biomarkers for evaluating optic nerve head morphology and for assisting in the diagnosis, staging, and longitudinal monitoring of glaucoma, myopia, and pathological myopia. Traditionally, the acquisition of these parameters has relied heavily on manual segmentation, which is limited by low efficiency, strong subjectivity, and considerable inter-observer variability. In recent years, artificial intelligence has been increasingly applied to OCT image segmentation, quality control, cross-device calibration, and automated quantitative analysis, thereby improving efficiency, objectivity, and reproducibility, particularly in eyes with complex optic disc morphology. This review summarizes recent advances in the BMO-related terminology standardization, imaging and quantitative methodologies, quality control,artificial intelligence-assisted analysis, as well as clinical evidence of its application in glaucoma, myopia and pathological myopia. Particular emphasis is placed on their potential value in the differential diagnosis and follow-up evaluation of highly myopic eyes with glaucoma, aiming to provide a reference for the standardized clinical application and future translational use of BMO-related parameters.

Acute pancreatitis is a common surgical emergency characterized by severe local or systemic complications during its progression. Diseases of the biliary system are among the serious local complications of acute pancreatitis, primarily including acute acalculous cholecystitis (AAC) and biliary stricture. AAC often occurs in the later stages of acute pancreatitis, exacerbating systemic inflammation and leading to organ failure and life-threatening conditions in severe cases. Biliary stricture is a rare but serious long-term complication of acute pancreatitis, which can induce cholangitis, progressive liver function impairment, and secondary biliary cirrhosis. Due to the clinical symptoms of acute pancreatitis that can mask biliary system diseases, some patients may not receive timely diagnosis and treatment for concurrent biliary issues during the onset of acute pancreatitis, which can be life-threatening in severe cases. Currently, the ideal treatment strategy for biliary system complications secondary to acute pancreatitis remains unclear, lacking definitive guidelines or consensus. This article integrates recent research developments from both domestic and international studies to elucidate the pathogenesis, diagnosis, and treatment strategies for biliary system complications secondary to acute pancreatitis.

Acute pancreatitis is a common surgical emergency characterized by severe local or systemic complications during its progression. Diseases of the biliary system are among the serious local complications of acute pancreatitis, primarily including acute acalculous cholecystitis (AAC) and biliary stricture. AAC often occurs in the later stages of acute pancreatitis, exacerbating systemic inflammation and leading to organ failure and life-threatening conditions in severe cases. Biliary stricture is a rare but serious long-term complication of acute pancreatitis, which can induce cholangitis, progressive liver function impairment, and secondary biliary cirrhosis. Due to the clinical symptoms of acute pancreatitis that can mask biliary system diseases, some patients may not receive timely diagnosis and treatment for concurrent biliary issues during the onset of acute pancreatitis, which can be life-threatening in severe cases. Currently, the ideal treatment strategy for biliary system complications secondary to acute pancreatitis remains unclear, lacking definitive guidelines or consensus. This article integrates recent research developments from both domestic and international studies to elucidate the pathogenesis, diagnosis, and treatment strategies for biliary system complications secondary to acute pancreatitis.

This review aimed to provide a comprehensive analysis of the etiology, epidemiology, pathology, and conventional treatment of heterotopic ossification (HO), especially emerging potential therapies. HO is the process of ectopic bone formation at non-skeletal sites. HO can be subdivided into two major forms, acquired and hereditary, with acquired HO predominating. Hereditary HO is a rare and life-threatening genetic disorder, but both acquired and hereditary form can cause severe complications, such as peripheral nerve entrapment, pressure ulcers, and disability if joint ankylosis develops, which heavily contributes to a reduced quality of life. Modalities have been proposed to treat HO, but none have emerged as the gold standard. Surgical excision remains the only effective modality; however, the optimal timing is controversial and may cause HO recurrence. Recently, potential therapeutic strategies have emerged that focus on the signaling pathways involved in HO, and small molecule inhibitors have been shown to be promising. Moreover, additional specific targets, such as small interfering RNAs (siRNAs) and non-coding RNAs, could be used to effectively block HO or develop combinatorial therapies for HO.
Humans ; Ossification, Heterotopic/genetics*

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.
Humans ; Female ; Pregnancy ; Male ; Chromosomes, Human, Y/genetics* ; Adult ; Chromosome Deletion ; Pregnancy Outcome/genetics* ; Infertility, Male/genetics* ; Spermatozoa/physiology* ; Semen Analysis ; Sex Chromosome Disorders of Sex Development/genetics* ; Sperm Injections, Intracytoplasmic ; Azoospermia/genetics* ; Sex Chromosome Aberrations

OBJECTIVES: Neuropathic pain (NP) is one of the most common forms of chronic pain, yet current treatment options are limited in effectiveness. Peripheral nerve injury activates spinal microglia, altering their inflammatory response and phagocytic functions, which contributes to the progression of NP. Most current research on NP focuses on microglial inflammation, with relatively little attention to their phagocytic function. Early growth response factor 2 (EGR2) has been shown to regulate microglial phagocytosis, but its specific role in NP remains unclear. This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP, with the goal of identifying potential therapeutic targets. METHODS: Adult male Sprague-Dawley (SD) rats were used to establish a chronic constriction injury (CCI) model of the sciatic nerve. Pain behaviors were assessed on days 1, 3, 7, 10, and 14 post-surgery to confirm successful model induction. The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. Adeno-associated virus (AAV) was used to overexpress EGR2 in the spinal cord, and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP. CCI and lipopolysaccharide (LPS) models were established in animals and microglial cell lines, respectively, and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays. After confirming the involvement of microglial phagocytosis in NP, AAV was used to overexpress EGR2 in both in vivo and in vitro models, and phagocytic activity was further evaluated. Finally, eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify potential downstream effectors of EGR2. RESULTS: The CCI model successfully induced NP. Following CCI, EGR2 expression in the spinal cord was upregulated in parallel with NP development. Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats. Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis, which was further amplified by EGR2 overexpression. Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation. Among them, Lag3 emerged as a potential downstream target of EGR2. CONCLUSIONS EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.
Animals ; Microglia/metabolism* ; Phagocytosis/physiology* ; Rats, Sprague-Dawley ; Neuralgia/physiopathology* ; Early Growth Response Protein 2/metabolism* ; Male ; Rats ; Spinal Cord/metabolism* ; Sciatic Nerve/injuries*

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People