Objective: Based on spinopelvic parameters and biomechanical principles, the pedicle-facet joint (PFJ) morphological characteristics of isthmic and degenerative spondylolisthesis were analyzed, and the mechanism of their onset and progression was discussed. Methods: This retrospective cross-sectional study included 194 patients with L5 spondylolysis or L5–S1 low-grade isthmic spondylolisthesis (IS group), 172 patients with L4–5 degenerative spondylolisthesis (DS group), and 366 patients with nonlumbar spondylolysis (NL group). The spinopelvic parameters and PFJ morphological parameters of the patients were measured, the differences in these parameters among and within the 3 groups were compared, and the correlations were analyzed. Results: Sacral slope (SS) and lumbar lordosis (LL) were the highest in the IS group, the second highest in the DS group, and the lowest in the NL group. Among the 3 groups, the L4 facet joint angle (FJA) was the largest in the IS group, the second largest in the NL group, and the smallest in the DS group. The L4 pedicle-facet joint angle (PFA) was the largest in the DS group, the second largest in the IS group, and the smallest in the NL group. Pearson correlation analysis showed that within each group, SS and LL were negatively correlated with FJA and positively correlated with PFA. Conclusion This study found a correlation between the PFJ morphological characteristics of patients with lumbar spondylolisthesis and spinopelvic parameters, suggesting that the morphological characteristics of PFJs may be caused by varying stresses under different spinopelvic morphologies.

OBJECTIVE: To investigate short-term effectiveness of using expert adolescent lateral femoral nail (EALFN) in treating femoral shaft fractures in older children and adolescents. METHODS: A retrospective analysis was conducted on the clinical data of 17 patients with femoral shaft fractures who met the inclusion criteria and were admitted between July 2020 and June 2024. All fractures were fixed with EALFN after reduction. There were 11 males and 6 females, with a mean age of 13.3 years (range, 11-16 years). The average body weight was 51.2 kg (range, 40-84 kg), and the average height was 162.1 cm (range, 150-172 cm). The causes of injury included traffic accidents ( n=9), falling from height ( n=1), and simple falls ( n=7). One patient had an open fracture treated with an external fixator and experienced delayed fracture healing. The remaining patients were closed fractures, with an average time from injury to operation of 5.8 days (range, 2-10 days). Operation time and postoperative hospital stay were documented. During follow-up, X-ray films were taken to observe the fracture healing, and the bilateral femoral length, femoral neck-shaft angle, widest femoral neck diameter (FND), and articular trochanteric distance (ATD) were measured at last follow-up. Hip function was assessed using the Harris score. The differences in the all indicators between the healthy and affected sides were compared. RESULTS: The operation time ranged from 65 to 130 minutes (mean, 94.1 minutes). Postoperative hospital stay ranged from 5 to 40 days (mean, 16.7 days). All patients were followed up 7-36 months (mean, 14.4 months). One patient exhibited delayed fracture healing during follow-up. The distal locking nail was removed at 6 months after operation, and partial weight-bearing was initiated following dynamic fracture stabilization. The fracture healing was achieved, and the intramedullary nail was removed at 24 months after operation. The other fractures healed with the healing time of 6-20 months (mean, 9.6 months), and the intramedullary nails were removed. During follow-up, no femoral fracture, abnormal development of the greater trochanter, or ischemic necrosis of the femoral head occurred. At last follow-up, there was no significant difference in femoral length, femoral neck-shaft angle, FND, ATD, or Harris score between the affected and healthy sides ( P>0.05). CONCLUSION For older children and adolescents with femoral neck fractures, the application of EALFN fixation aligns more closely with the principles of intramedullary central fixation and rapid rehabilitation. This approach is associated with fewer complications and superior short-term effectiveness.
Humans ; Male ; Femoral Fractures/surgery* ; Female ; Child ; Adolescent ; Retrospective Studies ; Bone Nails ; Fracture Fixation, Intramedullary/instrumentation* ; Fracture Healing ; Treatment Outcome

OBJECTIVE: To review the research progress of three-dimensional (3D) bioprinting technology for wound dressing design and preparation. METHODS: The literature on 3D bioprinted wound dressings in recent years, both domestically and internationally, was retrieved. The core principles of 3D bioprinting technology, mainstream methods, and their applications in wound dressings design and preparation were summarized. RESULTS: By leveraging precise spatial manipulation capabilities and multi-material integration, 3D bioprinting technology constructs the functionalized wound dressings with complex structures and bioactivity. These dressings primarily function across several dimensions: wound hemostasis, infection control, controlled drug release, and monitoring wound healing. CONCLUSION Although 3D bioprinted wound dressings can promote wound healing through multiple dimensions, large-scale clinical validation is still lacking. Future efforts should further clarify their clinical value and scope of application to provide more efficient, precise, and patient-comfortable treatment options for refractory wounds .
Humans ; Wound Healing ; Printing, Three-Dimensional ; Bioprinting/methods* ; Bandages ; Tissue Engineering/methods* ; Tissue Scaffolds ; Biocompatible Materials

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

Icariin is a pure compound derived from Epimedium brevicornu Maxim, and it helps the regulation of male reproduction. Nevertheless, the role and underlying mechanisms of Icariin in mediating male germ cell development remain to be clarified. Here, we have demonstrated that Icariin promoted proliferation and DNA synthesis of mouse spermatogonial stem cells (SSCs). Furthermore, surface plasmon resonance iron (SPRi) and molecular docking (MOE) assays revealed that phosphodiesterase 5A (PDE5A) was an important target of Icariin in mouse SSCs. Mechanically, Icariin decreased the expression level of PDE5A. Interestingly, hydrogen peroxides (H 2 O 2 ) enhanced the expression level of phosphorylation H2A.X (p-H2A.X), whereas Icariin diminished the expression level of p-H2A.X and DNA damage caused by H 2 O 2 in mouse SSCs. Finally, our in vivo animal study indicated that Icariin protected male reproduction. Collectively, these results implicate that Icariin targets PDE5A to regulate mouse SSC viability and DNA damage and improves male reproductive capacity. This study thus sheds new insights into molecular mechanisms underlying the fate decisions of mammalian SSCs and offers a scientific basis for the clinical application of Icariin in male reproduction.
Male ; Animals ; Flavonoids/pharmacology* ; Mice ; Cyclic Nucleotide Phosphodiesterases, Type 5/drug effects* ; DNA Damage/drug effects* ; Cell Survival/drug effects* ; Cell Proliferation/drug effects* ; Spermatogonia/drug effects* ; Reproduction/drug effects* ; Adult Germline Stem Cells/metabolism* ; DNA Replication/drug effects*

Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly desired. Here, we discover that gossypol (GSP, a natural compound) dramatically enhances the chemosensitivity of cabazitaxel (CTX), even at previously ineffective concentrations. Based on this interesting finding, we exploit a carrier-free chemotherapeutic nano-booster for prostate cancer treatment, which is molecularly co-assembled by GSP and cabazitaxel (CTX). GSP not only readily forms nanoassembly with CTX, but also functions as a chemotherapeutic enhancer that unlocks an ultra-low-dose chemotherapeutic window. Not only that, precise dual-drug nanoassembly confers CTX a significantly larger maximum tolerable dose. As expected, the nano-booster exerts striking therapeutic benefits in mouse prostate tumor xenograft models. This study advances chemotherapeutic window expansion and self-sensitized chemotherapy toward clinical applicability.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective:To investigate the level of occupational health literacy (OHL) of key populations in Gansu Province in 2022, analyze the influencing factors, and provide a scientific basis for the formulation of health education measures for occupational populations.Methods:From April to December 2022, a stratified cluster random sampling method was adopted to select 11472 workers engaged in frontline jobs in 8 key industries across 86 counties and districts in Gansu Province as the research subjects. The "National Occupational Health Literacy Monitoring and Survey Personal Questionnaire" was used to investigate their OHL. The content includes basic demographic information and occupational health literacy level, and the chi-square test analysis was carried out by SPSS 23.0 software, and the influencing factors were analyzed by logistic regression analysis model.Results:In 2022, a total of 11 118 valid questionnaires were completed in Gansu Province, and the OHL level of key populations in Gansu Province was 48.3%. The OHL levels of occupational health legal knowledge, basic knowledge of occupational health protection, basic skills of occupational health protection and healthy working methods were 50.3%, 81.7%, 33.1% and 63.3%, respectively. In the eight key industries, the OHL level of workers from high to low is: ferrous and non-ferrous metal smelting and rolling processing industry (56.6%) , non-metallic mineral products industry (56.5%) , ferrous and non-ferrous metal mining and dressing industry (54.3%) , environmental sanitation industry (50.3%) , medical and health industry (49.9%) , education industry (40.9%) , transportation industry (40.4%) , and express delivery/takeaway delivery industry (23.3%) . The results of logistics regression analysis showed that gender, age, ethnicity, marital status, education level, average monthly income, nature and scale of employers, and length of service were the influencing factors of OHL level of front-line workers in eight industries in Gansu Province (all P<0.05) . Conclusion:In 2022, the OHL level of key populations in Gansu Province was 48.3%, which needs to be further improved. Occupational health publicity should be strengthened for low-income, low-educated, newly recruited, young and micro-enterprise occupational groups.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.