OBJECTIVES: To observe the therapeutic effect of spermine in neonatal mouse models of severe hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) infection and explore its therapeutic mechanism in light of regulation of macrophage GBP5/NLRP3 inflammasome pathway. METHODS: Neonatal BALB/c mice (3-5 days old) were divided into control group, EV71 infection group and Spermine treatment group. The mice in the latter two groups received an intraperitoneal injection of 50 μL EV71 suspension (1×10⁶ TCID50 of EV71), followed 3 days later by intraperitoneal injection of 50 μL PBS or 100 μmol/L spermine. GBP5, NLRP3, CXCL10, and TNFSF10 expressions in heart, liver, lung and kidney tissues of the mice were detected using Western blotting and qPCR, and tissue pathologies and macrophage infiltration were assessed with HE staining and immunohistochemistry. In cultured THP-1 and RAW264.7 cells, the effects of EV71 infection, GBP5 siRNA transfection and treatment with spermine or eflornithine on GBP5, NLRP3, CXCL10, and TNFSF10 mRNA expressions were investigated using qPCR. RESULTS: In the neonatal mice, EV71 infection resulted in multiple organ damage, macrophage infiltration and activation of the GBP5/NLRP3 pathway, and spermine treatment significantly improved tissue injuries, reduced macrophage infiltration, and down-regulated the expressions of GBP5, NLRP3 and the inflammatory factors in the infected mice. In THP-1 and RAW264.7 cells, EV71 infection caused significant upregulation of GBP5, NLRP3, CXCL10, and TNFSF10 expressions, which were obviously lowered by spermine treatment. In THP-1 cells, treatment with eflornithine significantly suppressed the reduction of GBP5, NLRP3, CXCL10, and TNFSF10 expressions induced by GBP5 siRNA transfection. CONCLUSIONS Spermine suppressed EV71 infection-induced inflammatory responses by inhibiting GBP5-mediated NLRP3 inflammasome activation, suggesting a new strategy for treatment of severe HFMD.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Mice ; Macrophages/metabolism* ; Enterovirus A, Human ; Mice, Inbred BALB C ; Inflammasomes/metabolism* ; Spermine/therapeutic use* ; Animals, Newborn ; Humans ; Enterovirus Infections ; Hand, Foot and Mouth Disease/drug therapy* ; RAW 264.7 Cells ; Chemokine CXCL10/metabolism*

OBJECTIVES: To investigate the causal relationship between gut microbiota and kidney stones. METHODS: Mendelian randomization analysis was conducted based on data from the MiBioGen consortium gut microbiota GWAS (exposure factors) and the IEU Open GWAS kidney stone dataset ukb-b-8297 (outcome variables) using the inverse variance weighted, MR-Egger regression, weighted median, weighted mode, and simple mode methods. Heterogeneity, pleiotropy, and leave-one-out sensitivity analyses were also performed. In the animal experiment, 12 male SD rats were randomized into control group with saline treatment and kidney stone model group treated with 1% ethylene glycol and 2% ammonium chloride for 28 consecutive days. Urine, blood, and intestinal samples of the rats were collected for testing the changes in renal function and intestinal barrier-related indicators, and kidney and colon pathologies were examined with histological staining and immunohistochemistry. The changes in diversity and abundance of gut microbiota were analyzed using 16S rRNA gene sequencing. RESULTS: Mendelian randomization analysis showed that decreased abundances of Lachnospiraceae NK4A136 group (OR=0.9974, 95% CI: 0.9948-0.9999, P=0.0393) and Gordonibacter (OR=0.9987, 95% CI: 0.9974-0.9999, P=0.0403) were associated with an increased risk of kidney stones without significant heterogeneity or horizontal pleiotropy, and sensitivity analyses suggested robustness of the results. The rat models of kidney stones exhibited significant renal function impairment and calcium oxalate crystal deposition, accompanied by decreased expressions of intestinal barrier-related proteins with lowered intestinal α- and β-diversity indices. Intestinal Gordonibacter abundance was significantly reduced in the rat models while the Lachnospiraceae NK4A136 group did not differ significantly between the control and model groups. CONCLUSIONS Decreased Gordonibacter abundance in gut microbiota is associated with an increased risk of kidney stones. The protective role of the Lachnospiraceae NK4A136 group against kidney stones as suggested by Mendelian randomization analysis fails to be supported by the experimental evidence and awaits further investigation.
Animals ; Kidney Calculi/microbiology* ; Gastrointestinal Microbiome ; Mendelian Randomization Analysis ; Rats, Sprague-Dawley ; Rats ; Male ; Disease Models, Animal ; Intestines/microbiology* ; RNA, Ribosomal, 16S/genetics*

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.

Objective:To investigate the perioperative adverse events and complications of flow-diverter devices in the treatment of unruptured intracranial aneurysms.Methods:This is a retrospective case series study. The clinical and imaging data of 174 patients with unruptured intracranial aneurysms treated with flow-diverter devices in the Department of Neurointervention, Department of Neurology, the First Medical Center of Chinese People′s Liberation Army General Hospital from January 2020 to January 2024 were retrospectively analyzed. There were 63 males and 111 females, with an age of (53.9±11.4) years (range:23 to 76 years).The occurrence, development and outcome of perioperative complications and related adverse events during treatment were collected and analyzed. The degree of aneurysm embolization was evaluated using the O′Kelly-Marotta (OKM) grading system,with OKM grade C and D as successful occlusion.Results:A total of 187 flow-diverter devices (from 7 different brands) were implanted in 174 patients (with 294 aneurysms). Of these, 151 cases involved standalone stent embolization, 26 cases involved stent embolization combined with coil assistance, and 5 cases involved the use of two flow-diverter devices simultaneously. Twenty-nine cases (16.7%,29/174) suffered intraoperative adverse events, including 10 cases of poor stents deployment, 3 cases of stents migration into the aneurysm sac, 1 cases of abnormal guidewire movement, 4 cases of ischemic events. Complications occurred in 10 patients (5.7%, 10/174), and neurological deficits occurred in 5 patients (2.9%, 5/174). A total of 129 patients completed follow-up for more than 12 months after surgery. There were 117 aneurysms with OKM grade D and 22 with OKM grade C, showing a satisfactory healing rate of 77.7% (139/179).Conclusion:The effect of flow-diverter devices in the treatment of intracranial aneurysms is satisfactory, but complications and adverse events cannot be ignored, especially the relatively high incidence of perioperative adverse events, which requires neurointerventional physicians to be vigilant.

Objective:To investigate the perioperative adverse events and complications of flow-diverter devices in the treatment of unruptured intracranial aneurysms.Methods:This is a retrospective case series study. The clinical and imaging data of 174 patients with unruptured intracranial aneurysms treated with flow-diverter devices in the Department of Neurointervention, Department of Neurology, the First Medical Center of Chinese People′s Liberation Army General Hospital from January 2020 to January 2024 were retrospectively analyzed. There were 63 males and 111 females, with an age of (53.9±11.4) years (range:23 to 76 years).The occurrence, development and outcome of perioperative complications and related adverse events during treatment were collected and analyzed. The degree of aneurysm embolization was evaluated using the O′Kelly-Marotta (OKM) grading system,with OKM grade C and D as successful occlusion.Results:A total of 187 flow-diverter devices (from 7 different brands) were implanted in 174 patients (with 294 aneurysms). Of these, 151 cases involved standalone stent embolization, 26 cases involved stent embolization combined with coil assistance, and 5 cases involved the use of two flow-diverter devices simultaneously. Twenty-nine cases (16.7%,29/174) suffered intraoperative adverse events, including 10 cases of poor stents deployment, 3 cases of stents migration into the aneurysm sac, 1 cases of abnormal guidewire movement, 4 cases of ischemic events. Complications occurred in 10 patients (5.7%, 10/174), and neurological deficits occurred in 5 patients (2.9%, 5/174). A total of 129 patients completed follow-up for more than 12 months after surgery. There were 117 aneurysms with OKM grade D and 22 with OKM grade C, showing a satisfactory healing rate of 77.7% (139/179).Conclusion:The effect of flow-diverter devices in the treatment of intracranial aneurysms is satisfactory, but complications and adverse events cannot be ignored, especially the relatively high incidence of perioperative adverse events, which requires neurointerventional physicians to be vigilant.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*

Microglia/physiology* ; Neurons/physiology* ; Cells, Cultured

Objective:To investigate the safety and effectiveness of Neuroform Atlas stent-assisted coiling in the endovascular treatment of intracranial aneurysms.Methods:This was a retrospective, single-center observational study of 77 patients who underwent endovascular treatment of intracranial aneurysms using the Neuroform Atlas device at the Department of Neurology, People′s Liberation Army General Hospital from July 2020 to May 2022. There were 34 males and 43 females, with a median (range) age of 59 (23-81) years. The degree and effect of aneurysm embolization were evaluated by modified Raymond grading post procedure and after 6 months. Complications occurring during the perioperative period were recorded. Vaso computed tomography was performed immediately after the operation to assess stent opening and adherence. Digital subtraction angiography was performed 6 months after discharge and the aneurysm was classified as cured, stable, or recurrent.Results:A total of 87 Atlases were successfully released in 77 cases. Angiography performed immediately after the embolization revealed 19 (24.7%) modified Raymond grade Ⅰ, 10 (13.0%) grade Ⅱ, and 48 (62.3%) grade Ⅲa cases. Three perioperative complications were observed including thrombotic events in 2 cases and stent migration in 1 case. A follow-up angiogram was available for 47 aneurysms, and showed that modified Raymond grade Ⅰ occlusion was achieved in 38 (80.9%) cases, grade Ⅱ in 2 (4.3%) cases, and grade Ⅲa in 7 (14.9%) cases. At the 6-month follow-up, 38 patients were cured and 7 were stable, whereas 2 patients experienced a recurrence of aneurysm. Stenosis of the parent artery occurred in 3 (6.4%) cases, including 2 at the head and 1 inside the stent.Conclusions:The results of this preliminary study suggest that Neuroform Atlas stent-assisted coiling has a high occlusion rate and low incidence of complications in the endovascular treatment of aneurysms. However, the effectiveness of this procedure for large aneurysms and long-term outcomes require further investigation.