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 To explore the significance of the toxicity mechanism of butyl benzyl phthalate(BBP)in prevention and treatment of pulmonary fibrosis.Methods In this study,we used network toxicology combined with molecular docking technology to screen the targets of BBP and those related to pulmonary fibrosis through PubChem,GeneCards and other databases,and analyzed the intersecting genes by using a Wayne diagram.Protein-protein interaction networks were constructed to screen the core targets,and the pathway mechanisms were revealed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.Finally,molecular docking using AutoDock was performed to verify the binding patterns of core targets and BBP.Results A total of 91 potential targets of BBP-induced lung fibrosis were screened,among which PTGS2 and CYP3A4 were the core targets(binding energies of-1.84 kcal/mol and-1.68 kcal/mol,respectively).Enrichment analysis showed that BBP regulated the fibrosis process through G protein-coupled receptor signaling pathway,calcium signaling pathway and cyclic adenosine monophosphate signaling pathway.Molecular docking confirmed that BBP was stably bound to the core target through hydrogen bonding and hydrophobic interaction.Conclusion This study provides preliminary insights into the molecular mechanism of BBP-induced pulmonary fibrosis through network toxicology,and PTGS2 and CYP3A4 may play key roles in BBP-induced pulmonary fibrosis,which provides a novel reference for the exploration of the mechanism of toxicant-disease association.

AIM To screen the material basis for Rhei Radix et Rhizoma on improving human umbilical vein endothelial cell(HUVECs)injury before and after carbonization.METHODS The HPLC fingerprints were established,after which difference analysis was performed by orthogonal partial least squares discriminant analysis.The LPS-induced HUVECs injury model was established,then NO,MDA levels and SOD activity were detected.Gray correlation analysis and partial least squares regression were adopted in the investigation of spectrum-effect relationship,and active constituents were screened.RESULTS There were 22 and 20 common peaks in the fingerprints for 17 batches of raw products and carbonized products,respectively,along with the similarities of more than 0.8.Twelve main difference components were observable,among which gallic acid,5-hydroxymethylfurfural,catechin,aloe rhodopsin-8-O-β-D-glucoside,rhubarbic acid-8-O-β-D-glucoside and sennosides A were identified.The carbonized products demonstrated stronger effect on improving HUVECs injury than the raw product.The correlations of common peaks were more than 0.5 in the fingerprints for raw products and carbonized products,and peaks 3,5,11,12,15,19,23 exhibited significant effects on their efficacy(VIP values＞1).CONCLUSION This accurate,reliable and reproducible method can provide a basis for clarifying the material basis for hemostatic efficacy of Rhei Radix et Rhizoma and its carbonized product.

Objective:To evaluate the service capability and operational efficiency of surgical departments in a hospital using data analysis models such as entropy weight TOPSIS and Boston matrix analysis, for references for optimizing medical resource allocation, promoting refined management and sustainable development of the hospital.Methods:The operational data of 24 surgical departments (A~X) in a tertiary public hospital in 2023 from its information system were extracted. The number of doctors, actual number of open beds, and average length of stay etc., were served as evaluation indicators. The TOPSIS and rank sum ratio methods were used to evaluate the medical service capabilities, the data envelopment analysis (DEA) was used to analyze operational efficiency, and Boston matrix analysis was used for departmental classification.Results:In terms of medical service capabilities, the top 5 departments were F, S, K, D, and C ( Ci>0.41), all of which were in the excellent category; The bottom three departments were L, N, and G ( Ci<0.04), all of which were in the poor range. From the perspective of operational efficiency, 8 departments had achieved strong DEA effectiveness, while the remaining 16 departments were non DEA effective, resulting in resource redundancy or insufficient output. According to the Boston Matrix analysis, 8 departments (stars) had strong medical service capabilities and high operational efficiency; 6 departments (cash cows) had poor medical service capabilities but high operational efficiency, and 8 departments (dogs) had poor medical service capabilities and operational efficiency; 2 departments (question marks) had strong medical service capabilities but low operational efficiency. Conclusions:This study comprehensively applied multiple data models to objectively and comprehensively evaluate the service capabilities and operational efficiency of surgical departments. Hospitals could develop corresponding resource allocation optimization strategies based on the Boston matrix classification results, combined with the disease characteristics and business scale configuration of each department.

Iodine speciations in aquatic environments are affected by dissolved oxygen,redox potential,microbial activity,organic matter decomposition,light reaction,etc.Accurate quantification of iodine speciation can not only help to understand the geochemical cycle of iodine,but also help to trace and study environmental processes.Based on the combination of ion chromatography(IC)and inductively coupled plasma mass spectrometry(ICP-MS),a rapid and sensitive method was established for determining the speciations of iodine in environmental water samples including seawater,river water,lake water,rainwater,groundwater,etc.The results presented here showed that IO3?and I?in seawater were quickly separated and measured within 120 s when using guard column AG22 and 8 mmol/L(NH4)2CO3 as the mobile phase.While for lake water,river water and precipitation samples with high soluble organically bond iodine(SOI),an AS22 separation column(250 mm×4 mm)connected with a guard column and using 50 mmol/L(NH4)2CO3 as mobile phase could effectively separate unknown SOI from IO3? to achieve accurate quantification of IO3?.For accurate correction of iodine measurement signal fluctuations,133Cs was directly added to the(NH4)2CO3 mobile phase as an internal standard.The SOI content was calculated by the total iodine concentrations minus the sum of IO3?and I?.The precision of the established iodine speciation analytical method was better than 3.5%,and the standard addition experiment showed that the analytical method was accurate.When the injection volume was 25 μL,the detection limits were 0.011?0.025 μg/L for IO3? and 0.023?0.031 μg/L for I?,respectively.The method was successfully used to analyze IO3?,SOI and I? in environmental water samples,such as seawater,river water,rainwater and groundwater.

PURPOSE: The retear rate of rotator cuff (RC) after surgery is high, and the rapid and functional enthesis regeneration remains a challenge. Whether acellular amniotic membrane (AAM) helps to promote the healing of tendon to bone and which treatment is better are both unclear. The study aims to investigate the effect of AAM on the healing of RC and the best treatment for RC repair. METHODS: Thirty-three Sprague Dawley rats underwent RC transection and repair using microsurgical techniques and were randomly divided into the suturing repair only (SRO) group (n = 11), the AAM overlaying (AOL) group (n = 11), and the AAM interposition (AIP) group (n = 11), respectively. Rats were sacrificed at 4 weeks, then examined by subsequent micro-CT, and evaluated by histologic and biomechanical tests. The statistical analyses of one-way ANOVA or Kruskal-Wallis test were performed using with SPSS 23.0. A p < 0.05 was considered a significant difference. RESULTS: AAM being intervened between tendon and bone (AIP group) or overlaid over tendon to bone junction (AOL group) in a rat model, promoted enthesis regeneration, increased new bone and cartilage generation, and improved collagen arrangement and biomechanical properties in comparison with suturing repair only (SRO group) (AOL vs. SRO, p < 0.001, p = 0.004, p = 0.003; AIP vs. SRO, p < 0.001, p < 0.001, p < 0.001). Compared with the AOL group, the AIP group had better results in micro-CT evaluation, histological score, and biomechanical testing (p = 0 0.039, p = 0.011, p = 0.003, respectively). CONCLUSION In the RC repair model, AAM enhanced regeneration of the tendon to bone junction. This regeneration was more effective when the AAM was intervened at the tendon to bone interface than overlaid above the tendon to bone junction.
Animals ; Rats, Sprague-Dawley ; Rotator Cuff Injuries/surgery* ; Amnion/transplantation* ; Rats ; Wound Healing ; Rotator Cuff/surgery* ; Male ; X-Ray Microtomography ; Tendons/surgery* ; Biomechanical Phenomena

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social impairments, repetitive behaviors, and restricted interests. Studies have shown that it is more prevalent in males than females. Although this issue has attracted academic attention since the 20th century, the specific mechanisms underlying the gender differences in ASD remain unclear. This paper reviews the impact of gender differences in ASD, focusing on the female protective effect, DNA methylation, hormone levels, and clinical manifestations. It also discusses corresponding treatment options, particularly suggesting improvements in the diagnostic process, which is often overlooked, in order to provide valuable references for the clinical diagnosis and treatment of ASD.
Humans ; Autism Spectrum Disorder/genetics* ; Female ; Male ; DNA Methylation ; Sex Factors ; Sex Characteristics

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*