AIM:To analyze the clinical phenotypes and genotypes of children with incontinentia pigmenti(IP)and enhance clinicians' understanding of the condition.METHODS: A family with IP diagnosed in February 2020 at the ophthalmology department of People's Hospital of Ningxia Hui Autonomous Region was enrolled. The proband and family members underwent comprehensive systemic and ocular examinations. Peripheral venous blood was collected for DNA extraction, followed by whole-exome sequencing and MLPA assay to identify pathogenic variants. Corresponding treatments were administered based on the severity of fundus lesions, and ocular clinical features and therapeutic outcomes were monitored during follow-up.RESULTS: The child in this study was a female, aged 8 years, with typical skin changes and scarring alopecia and dental abnormalities at the time of initial consultation. The results of genetic testing suggested that the child carried a heterozygous deletion of exons 4-10 of the IKBKG gene chrX:153440010-153446570del. The child had asymmetric lesions in both eyes, with severe lesions in the left eye, atrophy of the eyeballs, and ocular B-ultrasound suggesting structural disturbances in the eye, and neovascularization was seen in the peripheral retina of the right eye, and the patient was given laser photocoagulation treatment for the right eye, and no progression of retinopathy was detected during follow-up.CONCLUSION:Children with IP have different ocular clinical phenotypes, and retinal vasculopathy is the main change. Early screening and timely and standardized treatment are crucial for children diagnosed with IP.

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

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.

Demyelination and remyelination play key roles in spinal cord injury (SCI), affecting the recovery of motor and sensory functions. Research in rodent models is extensive, but the study of these processes in non-human primates is limited. Therefore, our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis. In a previous study, we created an SCI model in M. fascicularis by controlling the contusion displacement. We used Eriochrome Cyanine staining, immunohistochemical analysis, and toluidine blue staining to evaluate demyelination and remyelination. The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally, the former mainly impacting sensory pathways, while the latter primarily affected motor pathways. Toluidine blue staining showed myelin loss and axonal distension at the injury site. Schwann cell-derived myelin sheaths were only found at the center, while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas. Our study showed that long-lasting demyelination occurs in the spinal cord of M. fascicularis after SCI, with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.
Animals ; Spinal Cord Injuries/physiopathology* ; Demyelinating Diseases/etiology* ; Remyelination/physiology* ; Macaca fascicularis ; Disease Models, Animal ; Myelin Sheath/pathology* ; Oligodendroglia/pathology* ; Schwann Cells/pathology* ; Female ; Spinal Cord/pathology* ; Axons/pathology*

Objective:To explore the influencing factors for pneumonia occurrence within three months in patients undergoing partial laryngectomy combined with radiotherapy, and to construct a nomogram prediction model for the risk of pneumonia occurrence.Methods:A total of 165 patients with laryngeal squamous cell carcinoma who underwent partial laryngectomy combined with postoperative radiotherapy in the Affiliated Cancer Hospital of Zhengzhou University from 2017 to 2023 were divided into three groups: a group without pneumonia, a low risk pneumonia group, and a medium to high risk pneumonia group according to the occurrence of pneumonia. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff values of the mean dose to the larynx (Larynx-Dmean) and the mean dose to the pharyngeal constrictor muscles (PCM-Dmean) for predicting the occurrence of pneumonia. Logistic regression analysis was used to screen out the influencing factors of pneumonia within three months after partial laryngectomy combined with radiotherapy, and a nomogram prediction model was constructed.Results:Among the 165 patients, 59 were in the group without pneumonia, 60 were in the group with a low risk of pneumonia, and 46 were in the group with a medium to high risk of pneumonia. The overall incidence of pneumonia was 64.2% (106/165). ROC curve analysis showed that the area under the curve (AUC) of the Larynx-Dmean for predicting the occurrence of pneumonia was 0.876, and the optimal cutoff value was 60.8 Gy. When the Larynx-Dmean was >60.8 Gy, the incidence of pneumonia was 96.7%. The AUC of the PCM-Dmean for predicting the occurrence of pneumonia was 0.747, and the optimal cutoff value was 54.6 Gy. When the PCM-Dmean was >54.6 Gy, the incidence of pneumonia was 74.7%. The AUC of the Larynx-Dmean for predicting the occurrence of medium to high risk pneumonia was 0.987, and the optimal cutoff value was 68.2 Gy. When the Larynx-Dmean was >68.2 Gy, the incidence of medium to high risk pneumonia was 100.0%. The AUC of the PCM-Dmean for predicting the occurrence of medium to high risk pneumonia was 0.850, and the optimal cutoff value was 58.7 Gy. When the PCM-Dmean was >58.7 Gy, the incidence of medium to high risk pneumonia was 85.2%. Multivariate logistic regression analysis showed that the incidence of pneumonia was higher in patients with a history of smoking ( OR=1.54, 95% CI: 1.02-1.74), a higher smoking index ( OR=2.43, 95% CI: 1.16-7.59), a higher Larynx-Dmean ( OR=3.79, 95% CI: 1.25-6.49), and a higher PCM-Dmean ( OR=2.44, 95% CI: 1.53-3.16). A nomogram prediction model for the risk of pneumonia and medium to high risk pneumonia within three months after partial laryngectomy combined with radiotherapy was successfully constructed, with C indices of 0.78 and 0.98, respectively, which had good predictive performance and clinical efficacy. Conclusions:When the Larynx-Dmean was >60.8 Gy and the PCM-Dmean was >54.6 Gy for postoperative radiotherapy after partial laryngectomy, the possibility of pneumonia occurrence in patients within three months increased significantly. Smoking history, smoking index, Larynx-Dmean, and PCM-Dmean were independent influencing factors for the occurrence of pneumonia. The nomogram prediction model constructed based on this can guide clinicians to take intervention measures to prevent the occurrence of pneumonia in patients with laryngeal cancer.

Objective:To integrate the best available evidence regarding the management of perinatal intraventricular hemorrhage (IVH) in preterm infants.Methods:Using keywords such as "intracranial hemorrhage", "intraventricular hemorrhage", "germinal matrix hemorrhage", and their Chinese equivalents, we systematically searched for clinical decisions, guidelines, expert consensuses, evidence summaries, group standards, systematic reviews, and meta-analyses related to IVH management in preterm infants. Data sources included BMJ Best Practice, UpToDate, World Health Organization website, Guidelines International Network, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, Registered Nurses' Association of Ontario, National Guideline Clearinghouse, American Academy of Pediatrics, Canadian Paediatric Society, European Foundation for the Care of Newborn Infants, British Association of Perinatal Medicine, Yiigle, Cochrane Library, Joanna Briggs Institute, PubMed, Web of Science, CINAHL, MEDLINE, Embase, China National Knowledge Infrastructure, Wanfang Data, and SinoMed. The search period spanned from January 2015 to December 2024. Literature screening, quality appraisal, evidence extraction, and synthesis were performed independently according to uniform standards.Results:A total of 12 publications were included, comprising three clinical decisions, three evidence-based guidelines, and six expert consensuses. Thirty-seven best evidence statements were synthesized across four domains: risk factor identification, diagnosis and monitoring, antenatal and delivery room management, and neonatal intensive care unit management. These included 28 strong recommendations (Grade A) and nine weak recommendations (Grade B).Conclusion:The 37 summarized best evidence statements provide an evidence-based foundation for developing clinical management protocols for perinatal IVH in preterm infants.

The basic structure and working principle of the fluorine multifunctional module were described in brief.Six cases of common faults of the fluorine multifunctional module during automatic synthesis of 18F-PSMA were introduced in terms of the cause and maintenance.References were provided for treating similar faults.[Chinese Medical Equipment Journal,2025,46(2):112-116]

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective : To construct triggering receptor expressed on myeloid cells 2(TREM2) gene knockout(TREM2-/-) mice using CRISPR/Cas9 technology, to breed TREM2-/- mice and to analyze the genotype of TREM2-/- mice. Methods : CRISPR/Cas9 technology was used to selectively knock out exon 2-3 regions of TREM2 gene to construct a TREM2-/- mouse model, and the genetic background of all mice was C57BL/6J. Polymerase chain reaction(PCR) was used to identify the genotype of mice. Quantitative real-time PCR(qPCR) and Western blot were used to detect the expression level of TREM2 in major tissues of mice, and the authenticity and scientific nature of PCR identification results were verified from mRNA level and protein level. According to the sgRNA sequence, the possible off-target sites were predicted on the CCTop website, and the tail DNA of mice was extracted and amplified by PCR and then Sanger sequencing was performed to detect whether there was off-target effect in TREM2-/- mice. Results : TREM2-/- mice were successfully constructed by CRISPR/Cas9 technology, and the mice were genotyped. The results of agarose gel electrophoresis showed that the mouse genotype with only 415 bp band amplified was wild type(WT), the mouse genotype of the 449 bp band amplified only was TREM2-/-, and the mouse genotypes amplified with 415 bp and 449 bp double bands were heterozygous. qPCR results showed that compared with WT mice, the mRNA expression of TREM2 in heart and brain tissues of TREM2-/- mice was down-regulated(P-/- mice was reduced(P-/- mice. Conclusion TREM2-/- mice are successfully constructed and bred, a reliable genotype identification method is established, the genetic stability of the mouse model is verified, which will provide an important genetic animal model for the study of TREM2 gene function.