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*

BACKGROUND:Osteoporosis is often accompanied by sarcopenia and an increased risk of fractures from falls.Recent studies have indicated a close relationship between lipid metabolism and sarcopenia.Abnormal lipid metabolism may directly impact muscle physiological function and metabolism. OBJECTIVE:To investigate the relationship between lipid metabolism and sarcopenia and evaluate their causal relationship using Mendelian randomization. METHODS:Mendelian randomization was used to explore the causal relationship between low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,triglycerides,and muscle mass.Research data from genome-wide association studies were used and a sensitivity analysis was conducted to verify the reliability of the results.Approximate indicators of muscle mass,including trunk lean mass and appendicular lean mass,were used as outcome measures. RESULTS AND CONCLUSION:The study found a negative correlation of low-density lipoprotein cholesterol and triglycerides with muscle mass,while no correlation was observed between high-density lipoprotein cholesterol and muscle mass.The results of the sensitivity analysis indicated a robust causal relationship.Using Mendelian randomization,this study provides evidence of a causal relationship between low-density lipoprotein cholesterol and triglycerides and muscle mass.This finding deepens our understanding of the effects of lipids on sarcopenia and has important clinical implications for the prevention and treatment of sarcopenia and osteoporosis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the surgical effect of pedicled upper lip mucosal flap in repairing nasal septal mucosal defects after rhinoplasty.Methods:A retrospective analysis was performed from January 2016 to October 2022, the clinical data of patients with nasal septal mucosal defects after rhinoplasty were collected in the Department of Plastic and Aesthetic (Burn) Surgery at the Second Xiangya Hospital of Central South University. The pedicled upper lip mucosal flap was utilized for repair based on the patient’s medical history and wound condition. The pedicle of the flap was designed 1 cm adjacent to the frenulum of the upper lip, and an appropriate flap was incised based on the size of the wound, with dissection performed up to the superficial layer of the orbicularis oris muscle. The dissection establishes an upper lip tunnel that connects the gingival-buccal groove to the nasal cavity. The pedicled upper lip mucosal flap was elevated and transposed into the nasal cavity via the upper lip tunnel. The position of the flap was adjusted to ensure complete coverage and fixation of the nasal septal defect wound using 5-0 absorbable suture. The visual analogue scale (VAS) and the nasal obstruction symptom evaluation (NOSE) scale were utilized to facilitate patients’ satisfaction evaluation and assessment of nasal obstruction symptoms before surgery and at 6 months post-surgery. The VAS total score was 10 points, with higher scores indicating greater levels of patient satisfaction. The NOSE scale comprises of 5 items, each assigned a score ranging from 0 to 4, denoting absence of symptoms, very mild presence, moderate intensity, relatively severe manifestation, and highly severe indication respectively. The measurement data of VAS and NOSE scores before surgery and at 6 months post-surgery was expressed by Mean±SD, using paired t-test. The score distribution of the NOSE scale was represented by the number of cases, using Mann-Whitney U test. Results:The study included a total of 15 female patients, with an average age of (27.6±2.9) years (ranging from 23 to 33 years). Eleven cases presented with preoperative cartilage exposure, and the size of tissue defect ranged from 0.9 cm×0.5 cm to 1.5 cm×0.7 cm. Nine patients had a history of smoking. Skin grafting was performed in 9 patients, while nasal mucosal metastasis was observed in 8 patients. The dimensions of the flap varied from 4.0 cm×1.2 cm to 7.0 cm×1.5 cm. The postoperative recovery was satisfactory, with successful survival of the skin flaps and no occurrences of infection, hematoma, wound dehiscence, or flap necrosis. The average duration of follow-up was (8.2±2.1) months (ranging from 6 to 12 months). The postoperative VAS score (7.73±0.88) was significantly higher compared to the preoperative score (1.86±0.74) ( P<0.01). Additionally, the postoperative NOSE score (4.66±1.71) showed a significant decrease from the preoperative score (10.73±2.68), with a statistically significant difference ( P<0.01). Among them, after surgery items of stuffy or unbreathable nose (2 cases vs. 15 cases), nasal obstruction (1 case vs. 14 cases), and feeling that the nose was not enough to breathe during exercise or exertion (4 cases vs. 14 cases) scored≥2 points were significantly less than those before operation (all P<0.01). Conclusion:The utilization of pedicled upper lip mucosal flap in the reconstruction of severe nasal septal mucosal defects following rhinoplasty has proven to be highly effective. The postoperative satisfaction of patients is remarkably high, the ventilation function exhibits significant improvement, and no severe complications are observed.

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 evaluate the effectiveness of surgical methods for correcting pollybeak deformity in Chinese rhinoplasty.Methods:A retrospective chart review was conducted for patients who underwent pollybeak correction between January 2021 and December 2022 at the Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital of Central South University. Individualized correction was tailored based on the etiology and severity of the nasal deformity of each patient, involving techniques such as resection of the anterior part of the nasal septum, reconstruction of nasal tip support, reconstruction of the middle part of the nasal vault, and excision of skin in the upper region of the nasal tip. A modified classification system for pollybeak deformity, the supratip fullness rating scale (SFRS), was developed to evaluate supratip fullness (0-3 points, with higher scores indicating more apparent deformity). The patients aesthetic outcomes were assessed by surgeons using the visual analogue scale (VAS) (0-10 points, with higher scores indicating more apparent deformity), and patient self-assessed using the rhinoplasty outcome evaluation (ROE) questionnaire (0-100 points, with higher scores indicating higher satisfaction). The measurement data of normal distribution was expressed as Mean±SD and analyzed by paired t-test; the measurement data of non-normal distribution was expressed as M( Q1, Q3) and analyzed by Wilcoxon signed rank test. Results:In a cohort study of 53 rhinoplasty patients (7 male, 46 female; age range 19-45 years, mean 29 years), comprising 15 primary and 38 secondary surgeries, nasal tip deformities were evaluated. Deformities were classified as mild (5 cases), moderate (25 cases), and severe (23 cases). Over a follow-up period of 6-17 months (mean 9.5 months), significant aesthetic improvements in the nasal tip region were observed. The SFRS scores decreased from 2(2, 3) preoperatively to 0(0, 0) postoperatively ( Z = -6.58, P < 0.001), and VAS scores decreased from 7.47±1.73 to 1.79±1.67 ( t = -25.61, P < 0.001). High patient satisfaction was indicated by a mean ROE score of 82.45±11.55. No significant complications, such as nasal tip ptosis, skin necrosis, or scar hyperplasia, were reported. Conclusion:Selecting an appropriate surgical method based on the severity and cause of pollybeak deformity can achieve satisfactory outcomes. Post-operative patients exhibit significant aesthetic improvement in the upper nasal tip area, resulting in high patient satisfaction.

Objective:To evaluate the effectiveness of surgical methods for correcting pollybeak deformity in Chinese rhinoplasty.Methods:A retrospective chart review was conducted for patients who underwent pollybeak correction between January 2021 and December 2022 at the Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital of Central South University. Individualized correction was tailored based on the etiology and severity of the nasal deformity of each patient, involving techniques such as resection of the anterior part of the nasal septum, reconstruction of nasal tip support, reconstruction of the middle part of the nasal vault, and excision of skin in the upper region of the nasal tip. A modified classification system for pollybeak deformity, the supratip fullness rating scale (SFRS), was developed to evaluate supratip fullness (0-3 points, with higher scores indicating more apparent deformity). The patients aesthetic outcomes were assessed by surgeons using the visual analogue scale (VAS) (0-10 points, with higher scores indicating more apparent deformity), and patient self-assessed using the rhinoplasty outcome evaluation (ROE) questionnaire (0-100 points, with higher scores indicating higher satisfaction). The measurement data of normal distribution was expressed as Mean±SD and analyzed by paired t-test; the measurement data of non-normal distribution was expressed as M( Q1, Q3) and analyzed by Wilcoxon signed rank test. Results:In a cohort study of 53 rhinoplasty patients (7 male, 46 female; age range 19-45 years, mean 29 years), comprising 15 primary and 38 secondary surgeries, nasal tip deformities were evaluated. Deformities were classified as mild (5 cases), moderate (25 cases), and severe (23 cases). Over a follow-up period of 6-17 months (mean 9.5 months), significant aesthetic improvements in the nasal tip region were observed. The SFRS scores decreased from 2(2, 3) preoperatively to 0(0, 0) postoperatively ( Z = -6.58, P < 0.001), and VAS scores decreased from 7.47±1.73 to 1.79±1.67 ( t = -25.61, P < 0.001). High patient satisfaction was indicated by a mean ROE score of 82.45±11.55. No significant complications, such as nasal tip ptosis, skin necrosis, or scar hyperplasia, were reported. Conclusion:Selecting an appropriate surgical method based on the severity and cause of pollybeak deformity can achieve satisfactory outcomes. Post-operative patients exhibit significant aesthetic improvement in the upper nasal tip area, resulting in high patient satisfaction.

Objective:To investigate the surgical effect of pedicled upper lip mucosal flap in repairing nasal septal mucosal defects after rhinoplasty.Methods:A retrospective analysis was performed from January 2016 to October 2022, the clinical data of patients with nasal septal mucosal defects after rhinoplasty were collected in the Department of Plastic and Aesthetic (Burn) Surgery at the Second Xiangya Hospital of Central South University. The pedicled upper lip mucosal flap was utilized for repair based on the patient’s medical history and wound condition. The pedicle of the flap was designed 1 cm adjacent to the frenulum of the upper lip, and an appropriate flap was incised based on the size of the wound, with dissection performed up to the superficial layer of the orbicularis oris muscle. The dissection establishes an upper lip tunnel that connects the gingival-buccal groove to the nasal cavity. The pedicled upper lip mucosal flap was elevated and transposed into the nasal cavity via the upper lip tunnel. The position of the flap was adjusted to ensure complete coverage and fixation of the nasal septal defect wound using 5-0 absorbable suture. The visual analogue scale (VAS) and the nasal obstruction symptom evaluation (NOSE) scale were utilized to facilitate patients’ satisfaction evaluation and assessment of nasal obstruction symptoms before surgery and at 6 months post-surgery. The VAS total score was 10 points, with higher scores indicating greater levels of patient satisfaction. The NOSE scale comprises of 5 items, each assigned a score ranging from 0 to 4, denoting absence of symptoms, very mild presence, moderate intensity, relatively severe manifestation, and highly severe indication respectively. The measurement data of VAS and NOSE scores before surgery and at 6 months post-surgery was expressed by Mean±SD, using paired t-test. The score distribution of the NOSE scale was represented by the number of cases, using Mann-Whitney U test. Results:The study included a total of 15 female patients, with an average age of (27.6±2.9) years (ranging from 23 to 33 years). Eleven cases presented with preoperative cartilage exposure, and the size of tissue defect ranged from 0.9 cm×0.5 cm to 1.5 cm×0.7 cm. Nine patients had a history of smoking. Skin grafting was performed in 9 patients, while nasal mucosal metastasis was observed in 8 patients. The dimensions of the flap varied from 4.0 cm×1.2 cm to 7.0 cm×1.5 cm. The postoperative recovery was satisfactory, with successful survival of the skin flaps and no occurrences of infection, hematoma, wound dehiscence, or flap necrosis. The average duration of follow-up was (8.2±2.1) months (ranging from 6 to 12 months). The postoperative VAS score (7.73±0.88) was significantly higher compared to the preoperative score (1.86±0.74) ( P<0.01). Additionally, the postoperative NOSE score (4.66±1.71) showed a significant decrease from the preoperative score (10.73±2.68), with a statistically significant difference ( P<0.01). Among them, after surgery items of stuffy or unbreathable nose (2 cases vs. 15 cases), nasal obstruction (1 case vs. 14 cases), and feeling that the nose was not enough to breathe during exercise or exertion (4 cases vs. 14 cases) scored≥2 points were significantly less than those before operation (all P<0.01). Conclusion:The utilization of pedicled upper lip mucosal flap in the reconstruction of severe nasal septal mucosal defects following rhinoplasty has proven to be highly effective. The postoperative satisfaction of patients is remarkably high, the ventilation function exhibits significant improvement, and no severe complications are observed.

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*