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.

Growth and development-related diseases result from the interplay of biological, psychological, and social factors. The collaboration between healthcare, sports, and education sectors integrates multidisciplinary resources and strengths to promote standardized diagnostic and therapeutic processes. This approach establishes a comprehensive closed-loop system encompassing early screening and referral, diagnosis and comprehensive evaluation, intervention and support plan formulation, as well as long-term management andoutcome assessment. It provides systematic scientific support for the healthy growth of children and adolescents, shifting disease intervention to the subclinical stage. Against the backdrop of societal informatization and intelligent development, this diagnostic and therapeutic model not only safeguards the holistic health of children and adolescents but also offers novel perspectives and feasible pathways for managing growth and development-related diseases. The implementation of this systematic diagnostic and therapeutic paradigm presents an innovative solution with Chinese characteristics for addressing such conditions, while injecting new vitality into the advancement of national health initiatives.

The growth and development of children is an important stage for health, and its monitoringand intervention are related to the long-term development of individuals. The construction of a standardized and multi-dimensional database of pediatric growth and development-related diseases is an important basis for realizing precise diagnosis and treatment and health management. Based on the needs of clinical practice, this study proposes to establish a specialized database of pediatric growth and development-related diseases that integrates facial phenotypes and clinical diagnosis and treatment information. This study elaborates on the construction process, including data sources, data collection content, and the operation and management of the database; and proposes key points for quality control, including the establishment of quality control nodes, database construction standards, and a full-process quality control framework. The above ensure the integrity, logic and effectiveness of the data, so that the database can provide an objective basis for the screening and diagnosis of pediatric growth and development-related diseases. On the basis of scientific data management and strict quality control, the database will help reveal the patterns of children's growth and development, and promote the level of children's health management.

To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents.

To investigate the mediating role of vitamin D in the association between exerciseand triglyceride among adolescents, as well as its potential molecular mechanisms.

To investigate body composition and associated factors in adolescents undergoing long-term regular sports training.

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

OBJECTIVE: To summarize the methods of ankle hinge position design in the correction of clubfoot deformity by Ilizarov method, and to explore its application value in the prevention of ankle dislocation. METHODS: A retrospective study was conducted including 28 patients with rigid clubfoot deformity (34 feet) who met the selection criteria and admitted between September 2021 and December 2024. There were 19 males and 9 females with an average age of 31.8 years (range, 19-47 years). According to Dimeglio classification, there were 21 feet of degree Ⅲ and 13 feet of degree Ⅳ. The causes were traumatic sequelae in 9 cases, congenital foot deformity in 15 cases, spina bifida sequelae in 1 case, peripheral neuropathy in 1 case, and cerebral palsy sequelae in 2 cases. The malformation lasted from 6 to 46 years, with an average of 29.3 years. All patients were treated with Ilizarov circular external fixator, and the hinge position of ankle joint was planned according to the standard lateral X-ray film of foot and ankle and the principle of Ilizarov limb deformity correction center of rotation angulation (CORA) before operation. The 2008 International Clubfoot Study Group (ICFSG) scoring system was used to evaluate the efficacy. RESULTS: The deformity of rigid clubfoot was completely corrected in all patients, and the patients could walk with plantar weight-bearing, and the ankle weight-bearing walking significantly improved when compared with that before operation. There was no complication such as ankle dislocation, talus impact or extrusion, local skin necrosis, needle tract infection, or numbness of extremities during the correction process. All patients were followed up 5-39 months, with an average of 18.1 months. At last follow-up, according to the ICFSG scoring system, 23 feet were excellent, 10 feet were good, and 1 foot was fair, and the excellent and good rate was 97%. CONCLUSION Designing the position of the ankle hinge according to the principle of CORA can effectively avoid ankle dislocation, talus impingement, tibiotalar joint extrusion, and other ankle adverse events in the process of correcting clubfoot deformity, which has good application value in clinical practice.
Humans ; Male ; Female ; Clubfoot/diagnostic imaging* ; Ilizarov Technique/instrumentation* ; Adult ; Retrospective Studies ; External Fixators ; Ankle Joint/diagnostic imaging* ; Middle Aged ; Joint Dislocations/prevention & control* ; Treatment Outcome ; Young Adult

Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade (ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified; some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration (FDA) for clinical treatment. However, limited responses and immune-related adverse events (irAEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoplasms/drug therapy* ; Immunotherapy/methods* ; Animals

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].