Objective: To evaluate the intervention effect of school based salt reduction health education, so as to provide a scientific basis for constructing a more effective and sustainable salt reduction intervention model for children. Methods: According to a randomized controlled trial design, in June 2022, probability proportional to size sampling was used to select 501 second grade students (248 in the control group and 253 in the intervention group) from 10 primary schools in Zhenjiang (intervention group) and 10 primary schools in Yangzhou (control group), Jiangsu Province. An one year school based salt reduction health education intervention was implemented. This included 20 online and 8 offline health education sessions, monitoring of salt consumption in the canteen, and the establishment of a salt reduction environment on campus. The control group received no additional salt reduction interventions. A questionnaire survey and 24 hour urinary sodium test were conducted before and after the intervention. The difference in differences method was used to evaluate the intervention effect. Results: After the intervention, the intervention group showed significant net intervention effects in knowledge aspects, including knowing that primary school students consume less salt than adults ( OR=3.55,95%CI =1.69-7.47), daily salt intake of primary school students ( OR=6.64,95%CI =3.71-11.87), long term high salt intake leading to hypertension ( OR=6.83,95%CI =3.93-11.91), low salt intake not causing hair graying ( OR= 1.66 ,95%CI =1.00-2.75), salt content in food labels ( OR=4.56,95%CI =2.63-7.91), and common high salt foods ( OR=3.39,95%CI =1.87-6.14) (all P <0.05). In terms of attitude, the net intervention effect for having a positive attitude toward using less salt in home cooking was significantly increased ( OR=1.88,95%CI =1.13-3.12, P <0.05). There were no statistically significant net intervention effects for salt reduction related behaviors (all P >0.05). There was no statistically significant difference in the changes of 24 hour urinary sodium between the intervention group and the control group before and after intervention ( P >0.05). Conclusions School based salt reduction health education effectively improves students salt reduction knowledge and attitudes but has a limited effect on behavior change. The home-school collaboration should be strengthened, and the dietary environment should be optimized simultaneously.

Objective To investigate the anti-intrahepatic cholangiocarcinoma （ICC） activity and mechanism of 2-heptyl-3-hydroxy-4（1H）-quinolone （PQS）, a secondary metabolite of polar marine microorganisms. Methods Patient-derived organoid （PDO） models were established using intrahepatic cholangiocarcinoma （ICC） tumor tissues obtained from Renji Hospital, Shanghai Jiao Tong University School of Medicine. Hematoxylin and eosin （HE） staining was performed to assess the histomorphological characteristics of both patient ICC tissues and corresponding PDOs. Immunohistochemistry （IHC） was employed to evaluate CYP3a expression in patient ICC tissues and PDOs. The antiproliferative activity of PQS against stably passaged PDOs was determined using an adenosine triphosphate （ATP）-based bioluminescence assay, and dose-response curves were fitted to calculate the half-maximal inhibitory concentration （IC₅₀） for assessing the anti-ICC efficacy of PQS. In the human intrahepatic cholangiocarcinoma RBE cell model, the effects of PQS on RBE cell proliferation were evaluated by the cell counting kit-8 （CCK-8） assay; colony formation capacity was assessed by the plate colony formation assay; cell cycle distribution and apoptosis were analyzed by flow cytometry; and the protein expression levels of cyclin-dependent kinase 2（CDK2）, CDK4, RelA（p65）, and nuclear factor-κB1（p50） were detected by Western blotting. Results Two ICC PDO models were successfully established. Histomorphological observation revealed that the PDO tissues after serial passaging exhibited morphological features essentially consistent with the corresponding patient ICC tissues, both presenting as cystic vesicle-like structures. Immunohistochemical analysis demonstrated that CYP3a was expressed in both PDO tissues and patient ICC tissues. ATP-based bioluminescence assay results indicated that PQS effectively suppressed ATP content in PDO tissues, with a fitted dose-response curve yielding an IC₅₀ value of 2.49 µmol/L. In the RBE cell model, PQS inhibited RBE cell viability in a concentration-dependent manner, and the fitted dose-response curve yielded an IC₅₀ value of 1.05 µmol/L. Furthermore, PQS at concentrations of 1, 2, and 4 µmol/L significantly suppressed colony formation of RBE cells, arrested the cell cycle at the S phase, induced apoptosis, and downregulated the expression of proteins associated with the NF-κB signaling pathway. Conclusion ICC PDO models were successfully established, confirming the anti-ICC activity of PQS. PQS inhibited RBE cell proliferation, potentially via the NF-κB signaling pathway, by arresting the cell cycle at the S phase and inducing apoptosis of RBE cells

Objective To investigate the anti-intrahepatic cholangiocarcinoma （ICC） activity and mechanism of 2-heptyl-3-hydroxy-4（1H）-quinolone （PQS）, a secondary metabolite of polar marine microorganisms. Methods Patient-derived organoid （PDO） models were established using intrahepatic cholangiocarcinoma （ICC） tumor tissues obtained from Renji Hospital, Shanghai Jiao Tong University School of Medicine. Hematoxylin and eosin （HE） staining was performed to assess the histomorphological characteristics of both patient ICC tissues and corresponding PDOs. Immunohistochemistry （IHC） was employed to evaluate CYP3a expression in patient ICC tissues and PDOs. The antiproliferative activity of PQS against stably passaged PDOs was determined using an adenosine triphosphate （ATP）-based bioluminescence assay, and dose-response curves were fitted to calculate the half-maximal inhibitory concentration （IC₅₀） for assessing the anti-ICC efficacy of PQS. In the human intrahepatic cholangiocarcinoma RBE cell model, the effects of PQS on RBE cell proliferation were evaluated by the cell counting kit-8 （CCK-8） assay; colony formation capacity was assessed by the plate colony formation assay; cell cycle distribution and apoptosis were analyzed by flow cytometry; and the protein expression levels of cyclin-dependent kinase 2（CDK2）, CDK4, RelA（p65）, and nuclear factor-κB1（p50） were detected by Western blotting. Results Two ICC PDO models were successfully established. Histomorphological observation revealed that the PDO tissues after serial passaging exhibited morphological features essentially consistent with the corresponding patient ICC tissues, both presenting as cystic vesicle-like structures. Immunohistochemical analysis demonstrated that CYP3a was expressed in both PDO tissues and patient ICC tissues. ATP-based bioluminescence assay results indicated that PQS effectively suppressed ATP content in PDO tissues, with a fitted dose-response curve yielding an IC₅₀ value of 2.49 µmol/L. In the RBE cell model, PQS inhibited RBE cell viability in a concentration-dependent manner, and the fitted dose-response curve yielded an IC₅₀ value of 1.05 µmol/L. Furthermore, PQS at concentrations of 1, 2, and 4 µmol/L significantly suppressed colony formation of RBE cells, arrested the cell cycle at the S phase, induced apoptosis, and downregulated the expression of proteins associated with the NF-κB signaling pathway. Conclusion ICC PDO models were successfully established, confirming the anti-ICC activity of PQS. PQS inhibited RBE cell proliferation, potentially via the NF-κB signaling pathway, by arresting the cell cycle at the S phase and inducing apoptosis of RBE cells

As China accelerates its efforts in deep space exploration and long-duration space missions, including the operationalization of the Tiangong Space Station and the development of manned lunar missions, safeguarding astronauts’ physiological and cognitive functions under extreme space conditions becomes a pressing scientific imperative. Among the multifactorial stressors of spaceflight, microgravity emerges as a particularly potent disruptor of neurobehavioral homeostasis. Dopamine (DA) plays a central role in regulating behavior under space microgravity by influencing reward processing, motivation, executive function and sensorimotor integration. Changes in gravity disrupt dopaminergic signaling at multiple levels, leading to impairments in motor coordination, cognitive flexibility, and emotional stability. Microgravity exposure induces a cascade of neurobiological changes that challenge dopaminergic stability at multiple levels: from the transcriptional regulation of DA synthesis enzymes and the excitability of DA neurons, to receptor distribution dynamics and the efficiency of downstream signaling pathways. These changes involve downregulation of tyrosine hydroxylase in the substantia nigra, reduced phosphorylation of DA receptors, and alterations in vesicular monoamine transporter expression, all of which compromise synaptic DA availability. Experimental findings from space analog studies and simulated microgravity models suggest that gravitational unloading alters striatal and mesocorticolimbic DA circuitry, resulting in diminished motor coordination, impaired vestibular compensation, and decreased cognitive flexibility. These alterations not only compromise astronauts’ operational performance but also elevate the risk of mood disturbances and motivational deficits during prolonged missions. The review systematically synthesizes current findings across multiple domains: molecular neurobiology, behavioral neuroscience, and gravitational physiology. It highlights that maintaining DA homeostasis is pivotal in preserving neuroplasticity, particularly within brain regions critical to adaptation, such as the basal ganglia, prefrontal cortex, and cerebellum. The paper also discusses the dual-edged nature of DA plasticity: while adaptive remodeling of synapses and receptor sensitivity can serve as compensatory mechanisms under stress, chronic dopaminergic imbalance may lead to maladaptive outcomes, such as cognitive rigidity and motor dysregulation. Furthermore, we propose a conceptual framework that integrates homeostatic neuroregulation with the demands of space environmental adaptation. By drawing from interdisciplinary research, the review underscores the potential of multiple intervention strategies including pharmacological treatment, nutritional support, neural stimulation techniques, and most importantly, structured physical exercise. Recent rodent studies demonstrate that treadmill exercise upregulates DA transporter expression in the dorsal striatum, enhances tyrosine hydroxylase activity, and increases DA release during cognitive tasks, indicating both protective and restorative effects on dopaminergic networks. Thus, exercise is highlighted as a key approach because of its sustained effects on DA production, receptor function, and brain plasticity, making it a strong candidate for developing effective measures to support astronauts in maintaining cognitive and emotional stability during space missions. In conclusion, the paper not only underscores the centrality of DA homeostasis in space neuroscience but also reflects the authors’ broader academic viewpoint: understanding the neurochemical substrates of behavior under microgravity is fundamental to both space health and terrestrial neuroscience. By bridging basic neurobiology with applied space medicine, this work contributes to the emerging field of gravitational neurobiology and provides a foundation for future research into individualized performance optimization in extreme environments.

Objective To investigate the efficacy of leaflet augmentation technique to repair the recurrent mitral valve (MV) regurgitation after mitral repair in children. Methods A retrospective analysis was conducted on the clinical data of children who underwent redo MV repair for recurrent regurgitation after initial MV repair, using a leaflet augmentation technique combined with a standardized repair strategy at Fuwai Hospital, Chinese Academy of Medical Sciences, from 2018 to 2022. The pathological features of the MV, key intraoperative procedures, and short- to mid-term follow-up outcomes were analyzed. Results A total of 24 patients (12 male, 12 female) were included, with a median age of 37.6 (range, 16.5–120.0) months. The mean interval from the initial surgery was (24.9±17.0) months. All children had severe mitral regurgitation preoperatively. The cardiopulmonary bypass time was (150.1±49.5) min, and the aortic cross-clamp time was (94.0±24.2) min. There were no early postoperative deaths. During a mean follow-up of (20.3±9.1) months, 3 (12.5%) patients developed moderate or severe mitral regurgitation (2 severe, 1 moderate). One (4.2%) patient died during follow-up, and one (4.2%) patient underwent a second MV reoperation. The left ventricular end-diastolic diameter was significantly reduced postoperatively compared to preoperatively [ (43.5±8.6) mm vs. (35.8±7.8)mm, P<0.001]. Conclusion The leaflet augmentation technique combined with a standardized repair strategy can achieve satisfactory short- to mid-term outcomes for the redo mitral repair after previous MV repair. It can be considered a safe and feasible technical option for cases with complex valvular lesions and severe pathological changes.

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*

OBJECTIVES: To explore the efficacy and adverse reactions of nusinersen combined with risdiplam in the treatment of spinal muscular atrophy (SMA). METHODS: A retrospective analysis was conducted on the clinical data of 10 pediatric SMA patients treated with nusinersen combined with risdiplam at the Children's Medical Center of Xiangya Hospital, Central South University. RESULTS: Among the 10 SMA patients, there were 4 with type I, 4 with type II, and 2 with type III. Nine patients initially received nusinersen monotherapy, while 1 patient received nusinersen combined with risdiplam. The median duration of combination therapy with nusinersen and risdiplam for the 10 patients was 10.5 months (range: 0.5-20.0 months), with 6 patients undergoing combination therapy for more than 6 months, showing improvements in motor and/or respiratory function. The remaining 4 patients had combination treatment durations of 0.5, 1.0, 1.3, and 4.0 months, respectively, with no significant overall improvement. After combined treatment, 5 patients experienced skin hyperpigmentation, 2 had lumbar puncture site pain, 1 experienced vomiting, 1 had increased sputum production, and 1 had reduced total sleep time. All adverse reactions were mild and did not require medical intervention. CONCLUSIONS Nusinersen combined with risdiplam demonstrates efficacy in the treatment of SMA, and no significant adverse reactions have been observed.
Humans ; Oligonucleotides/adverse effects* ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Infant ; Muscular Atrophy, Spinal/drug therapy* ; Drug Therapy, Combination ; Child ; Azo Compounds ; Pyrimidines

OBJECTIVE: To investigate the regulatory effects of two traditional mineral medicines (TMMs), Gypsum Fibrosum (Shigao, GF) and Terra Flava Usta (Zaoxintu, TFU), on gut-beneficial bacteria in mice, and preliminarily explore their mechanisms of action. METHODS: Mice were randomly divided into 3 groups (n=10 per group): the control group (standard diet), the GF group (diet supplemented with 2% GF), and the TFU group (diet supplemented with 2% TFU). After 4-week intervention, 16S rRNA gene sequencing was used to analyze the changes in the gut microbiota (GM). Scanning electron microscopy, in combination with coumarin A tetramethyl rhodamine conjugate and Hoechst stainings, was used to observe the bacteria and biofilm formation. RESULTS: Principal coordinate analysis revealed that GF and TFU significantly altered the GM composition in mice. Further analysis revealed that GF and TFU affected different types of gut bacteria, suggesting that different TMMs may selectively modulate specific bacterial populations. For certain bacteria, such as Faecalibaculum and Ileibacterium, both GF and TFU exhibited growth-promoting effects, implying that they may be sensitive to TMMs and that different TMMs can increase their abundance through their respective mechanisms. Notably, Lactobacillus reuteri, a widely recognized and used probiotic, was significantly enriched in the GF group. Random forest analysis identified Ileibacterium valens as a potential indicator bacterium for TMMs' impact on GM. Further mechanistic studies showed that gut bacteria formed biofilm structures on the TFU surface. CONCLUSIONS This study provides new insights into the interaction between TMMs and GM. As safe and effective natural clays, GF and TFU hold promise as potential candidates for prebiotic development.
Animals ; Gastrointestinal Microbiome/drug effects* ; Bacteria/growth & development* ; Mice ; Biofilms/drug effects* ; Male ; RNA, Ribosomal, 16S/genetics*

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry