ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Objective: This study aims to evaluate the clinical benefits of the integrated optical and magnetic surgical navigation system in assisting transforaminal endoscopic lumbar discectomy (TELD) for the treatment of lumbar disc herniation (LDH). Methods: A retrospective analysis was conducted on patients who underwent TELD for LDH at Beijing Chaoyang Hospital, Capital Medical University from November 2022 to December 2023. Patients treated with the integrated optical and magnetic surgical navigation system were defined as the navigation-guided TELD (Ng-TELD) group (30 cases), while those treated with the conventional x-ray fluoroscopy method were defined as the control group (31 cases). Record and compare baseline characteristics, surgical parameters, efficacy indicators, and adverse events between the 2 patient groups. Results: The average follow-up duration for the 61 patients was 11.8 months. Postoperatively, both groups exhibited significant relief from back and leg pain, which continued to improve over time. At the final follow-up, patients’ lumbar function and quality of life had significantly improved compared to preoperative levels (p < 0.05). The Ng-TELD group had significantly shorter total operation time (58.43 ± 12.37 minutes vs. 83.23 ± 25.90 minutes), catheter placement time (5.83 ± 1.09 minutes vs. 15.94 ± 3.00 minutes), decompression time (47.17 ± 11.98 minutes vs. 67.29 ± 24.23 minutes), and fewer intraoperative fluoroscopies (3.20 ± 1.45 vs. 16.58 ± 4.25) compared to the control group (p < 0.05). There were no significant differences between the groups in terms of efficacy evaluation indicators and hospital stay. At the final follow-up, the excellent and good rate of surgical outcomes assessed by the MacNab criteria was 98.4%, and the overall adverse event rate was 8.2%, with no statistically significant differences between the groups (p > 0.05). Conclusion This study demonstrates that the integrated optical and magnetic surgical navigation system can reduce the complexity of TELD, shorten operation time, and minimize radiation exposure for the surgeon, highlighting its promising clinical potential.

Objective: This study aims to evaluate the clinical benefits of the integrated optical and magnetic surgical navigation system in assisting transforaminal endoscopic lumbar discectomy (TELD) for the treatment of lumbar disc herniation (LDH). Methods: A retrospective analysis was conducted on patients who underwent TELD for LDH at Beijing Chaoyang Hospital, Capital Medical University from November 2022 to December 2023. Patients treated with the integrated optical and magnetic surgical navigation system were defined as the navigation-guided TELD (Ng-TELD) group (30 cases), while those treated with the conventional x-ray fluoroscopy method were defined as the control group (31 cases). Record and compare baseline characteristics, surgical parameters, efficacy indicators, and adverse events between the 2 patient groups. Results: The average follow-up duration for the 61 patients was 11.8 months. Postoperatively, both groups exhibited significant relief from back and leg pain, which continued to improve over time. At the final follow-up, patients’ lumbar function and quality of life had significantly improved compared to preoperative levels (p < 0.05). The Ng-TELD group had significantly shorter total operation time (58.43 ± 12.37 minutes vs. 83.23 ± 25.90 minutes), catheter placement time (5.83 ± 1.09 minutes vs. 15.94 ± 3.00 minutes), decompression time (47.17 ± 11.98 minutes vs. 67.29 ± 24.23 minutes), and fewer intraoperative fluoroscopies (3.20 ± 1.45 vs. 16.58 ± 4.25) compared to the control group (p < 0.05). There were no significant differences between the groups in terms of efficacy evaluation indicators and hospital stay. At the final follow-up, the excellent and good rate of surgical outcomes assessed by the MacNab criteria was 98.4%, and the overall adverse event rate was 8.2%, with no statistically significant differences between the groups (p > 0.05). Conclusion This study demonstrates that the integrated optical and magnetic surgical navigation system can reduce the complexity of TELD, shorten operation time, and minimize radiation exposure for the surgeon, highlighting its promising clinical potential.

Objective: This study aims to evaluate the clinical benefits of the integrated optical and magnetic surgical navigation system in assisting transforaminal endoscopic lumbar discectomy (TELD) for the treatment of lumbar disc herniation (LDH). Methods: A retrospective analysis was conducted on patients who underwent TELD for LDH at Beijing Chaoyang Hospital, Capital Medical University from November 2022 to December 2023. Patients treated with the integrated optical and magnetic surgical navigation system were defined as the navigation-guided TELD (Ng-TELD) group (30 cases), while those treated with the conventional x-ray fluoroscopy method were defined as the control group (31 cases). Record and compare baseline characteristics, surgical parameters, efficacy indicators, and adverse events between the 2 patient groups. Results: The average follow-up duration for the 61 patients was 11.8 months. Postoperatively, both groups exhibited significant relief from back and leg pain, which continued to improve over time. At the final follow-up, patients’ lumbar function and quality of life had significantly improved compared to preoperative levels (p < 0.05). The Ng-TELD group had significantly shorter total operation time (58.43 ± 12.37 minutes vs. 83.23 ± 25.90 minutes), catheter placement time (5.83 ± 1.09 minutes vs. 15.94 ± 3.00 minutes), decompression time (47.17 ± 11.98 minutes vs. 67.29 ± 24.23 minutes), and fewer intraoperative fluoroscopies (3.20 ± 1.45 vs. 16.58 ± 4.25) compared to the control group (p < 0.05). There were no significant differences between the groups in terms of efficacy evaluation indicators and hospital stay. At the final follow-up, the excellent and good rate of surgical outcomes assessed by the MacNab criteria was 98.4%, and the overall adverse event rate was 8.2%, with no statistically significant differences between the groups (p > 0.05). Conclusion This study demonstrates that the integrated optical and magnetic surgical navigation system can reduce the complexity of TELD, shorten operation time, and minimize radiation exposure for the surgeon, highlighting its promising clinical potential.

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*

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

This article reports a child with cardioaciocutaneous syndrome (CFCS) caused by a rare microdeletion of chromosome 19p13.3, and a literature review is conducted. The child had unusual facies, short stature, delayed mental and motor development, macrocephaly, and cardiac abnormalities. Whole-exome sequencing identified a 1 040 kb heterozygous deletion in the 19p13.3 region of the child, which was rated as a "pathogenic variant". This is the first case of CFCS caused by a loss-of-function mutation reported in China, which enriches the genotype characteristics of CFCS. It is imperative to enhance the understanding of CFCS in children. Early identification based on its clinical manifestations should be pursued, and genetic testing should be performed to facilitate diagnosis.
Humans ; Chromosome Deletion ; Chromosomes, Human, Pair 19/genetics* ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive/genetics* ; Heart Defects, Congenital/genetics*

OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

Immune checkpoint blockade therapy has demonstrated remarkable efficacy in treating various malignancies; however, its clinical application remains challenged by low response rates and immune-related adverse events. Immunoglobulin superfamily member 11 (IGSF11), an inhibitory immune checkpoint molecule, serves as a specific ligand for the V-domain immunoglobulin suppressor of T cell activation (VISTA). Through the IGSF11/VISTA axis, it suppresses T cell function and represents a promising novel target for cancer immunotherapy. IGSF11 is widely expressed across multiple tumor types, though its regulatory mechanisms vary depending on the malignancy. Studies have confirmed that blocking the IGSF11-VISTA interaction or specifically inhibiting IGSF11 exerts antitumor effects. While IGSF11 is closely associated with patient prognosis, its prognostic significance differs among cancer types. This review systematically summarizes the structural characteristics of IGSF11, its regulatory mechanisms, interaction with VISTA, and functional role within the tumor microenvironment.
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Humans ; Immunotherapy ; Neoplasms/metabolism* ; B7 Antigens/chemistry* ; Animals ; Molecular Targeted Therapy ; Tumor Microenvironment