ObjectiveTo investigate the effects of lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） gene G501C on brain structure and cognitive function in patients with white matter hyperintensities （WMH）. MethodsA total of 118 patients with WMH were enrolled. All participants underwent T1-weighted and T2-fluid-attenuated inversion recovery （T2-FLAIR） MRI to assess gray matter structure and WMH burden， and completed the mini-mental state examination （MMSE） and Montreal cognitive assessment （MoCA）. Partial correlation and mediation analyses were performed to explore the impact of LOX-1 polymorphism on cognitive function. ResultsParticipants were divided into GG+GC group （n = 35） and CC group （n = 83）. The GG+GC group showed lower MMSE and MoCA scores （MMSE： P=0.003； MOCA： P=0.015）， as well as greater WMH burden （all P0.001）， compared with the CC group. Voxel-based morphometry （VBM） analysis revealed reduced left thalamic volume in the GG+GC group， which was correlated with cognitive scores （all P0.05）. Subregional thalamic analysis further showed volume reductions in the lateral， ventral， medial， and pulvinar thalamic regions （all P0.05） in the GG+GC group， all positively associated with cognitive performance （all P0.05）. Mediation analyses indicated that volumes of the medial and pulvinar thalamic regions mediated the association between genotype and cognitive function （MMSE， MoCA）， and that WMH volume mediated the effect on MoCA scores. ConclusionThe LOX-1 G501C polymorphism may indirectly affect cognitive function by influencing specific thalamic subregional volumes and white matter damage， suggesting a potential mediating role of thalamic structures between genetic background and cognitive impairment.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

OBJECTIVES: To develop an early atrial fibrillation (AF) risk prediction model based on large-scale electrocardiogram (ECG) data from the Chinese population. METHODS: The data of multiple ECG records of 30 383 patients admitted in the Chinese PLA General Hospital between 2009 and 2023 were randomly divided into the training set and the internal testing set in a 7:3 ratio. The predictive factors were selected based on the training set using univariate analysis, LASSO regression, and the Boruta algorithm. Cox proportional hazards regression was used to establish the ECG model and the composite model incorporating age, gender, and ECG model score. The discrimination power, calibration, and clinical net benefits of the models were evaluated using the area under the receiver operating characteristic curve (AUROC), calibration curves, and decision curves. RESULTS: The cohort included 51.1% male patients with a median age of the patients of 51 (36, 62) years and an AF incidence of 4.5% (1370/30 383). In the ECG model, the parameters related to the P wave and QRS complex were identified as significant predictors. In the testing set, the AUROC of the ECG model for predicting 5-year AF risk was 0.77 (95% CI: 0.74-0.80), which was increased to 0.81 (95% CI: 0.78-0.83) after incorporating age and gender, with a net reclassification improvement of 0.123 and an integrated discrimination improvement of 0.04 (P<0.05). The calibration curve of the model was close to the diagonal line. Decision curve analysis showed that the clinical net benefit of the composite model was higher than that of the ECG model across the majority of threshold probability. CONCLUSIONS The composite model incorporating quantitative ECG features during sinus rhythm, along with age and gender, can effectively predict AF risk in the Chinese population, thus providing a low-cost screening tool for early AF risk assessment and management.
Humans ; Atrial Fibrillation/epidemiology* ; Electrocardiography ; Middle Aged ; Male ; Female ; China/epidemiology* ; Proportional Hazards Models ; Adult ; Risk Factors ; Risk Assessment ; East Asian People

OBJECTIVE: To analyze the effectiveness of three internal fixation methods, namely hollow screw combined with Kirschner wire tension band, hollow screw combined with anchor nail, and modified 1/3 tubular steel plate, in the treatment of avulsion fracture of tibial tubercle (AFTT) in adolescents. METHODS: Between January 2018 and September 2023, 19 adolescent AFTT patients who met the selection criteria were admitted. According to different internal fixation methods, patients were divided into group A (8 cases, hollow screw combined with Kirschner wire tension band), group B (6 cases, hollow screw combined with anchor nail), and group C (5 cases, modified 1/3 tubular steel plate). There was no significant difference in the baseline data of age, gender, side, cause of injury, Ogden classification, and time from injury to operation among the three groups ( P>0.05). The range of motion (ROM), weight-bearing time, normal activity time of knee joint, and the hospital for special surgery (HSS) score at last follow-up were recorded and compared among the three groups. Recorded whether the fracture was displaced, whether the fracture line was blurred at 1 month after operation, whether there was epiphyseal dysplasia, and whether there was incision infection and other complications. RESULTS: There was no significant difference in hospital stay between the groups ( P>0.05). All patients were followed up 10-24 months, with an average of 14.3 months; there was no significant difference between the groups ( P>0.05). All the incisions healed well without soft tissue irritation or fracture nonunion, and no limb shortening deformity or epiphyseal dysplasia was found during follow-up. At 1 month after operation, the knee joint ROM and hospitalization expenses in group A were better than those in groups B and C, the fracture healing time, knee joint weight-bearing time, and normal activity time of knee joint were better than those in group C, and the hospitalization expenses in group C were better than those in group B, with significant differences ( P<0.05); there was no significant difference in the other indicators between the groups ( P>0.05). In group A, the fracture line was blurred 1 month postoperatively, the fracture ends were in close contact, and there was no fracture displacement; in groups B and C, the fracture line was clear in 2 cases, and 1 case in group C had slight fracture displacement; except for 1 case in group B, there was no fracture split in the other two groups. There was no significant difference in the incidences of blur of fracture line, fracture displacement, and intraoperative bone split between the groups at 1 month after operation ( P>0.05). At last follow-up, the HSS scores of knee joints in the three groups were excellent and good, and there was no significant difference between the groups ( P>0.05). CONCLUSION Hollow screw combined with Kirschner wire tension band technique is effective in treating adolescent AFTT, which has the advantages of stabilizing fracture, accelerating fracture healing and rehabilitation, early feasible knee joint functional exercise, and reducing hospitalization expenses.
Humans ; Tibial Fractures/surgery* ; Adolescent ; Male ; Fracture Fixation, Internal/instrumentation* ; Female ; Fractures, Avulsion/surgery* ; Bone Wires ; Bone Screws ; Bone Plates ; Treatment Outcome ; Range of Motion, Articular ; Bone Nails ; Weight-Bearing ; Fracture Healing

OBJECTIVE: To explore effectiveness of intermediate screw assisted reduction and fixation technique in the treatment of Schatzker type Ⅴ and Ⅵ tibial plateau fractures. METHODS: A clinical data of 22 patients with Schatzker type Ⅴ and Ⅵ tibial plateau fractures, who were admitted between June 2022 and December 2023 and met the selection criteria, was retrospectively analyzed. During operation, the intermediate screw assisted reduction and fixation technique was used. There were 14 males and 8 females with an average age of 46.3 years (range, 17-65 years). The fractures were caused by traffic accident in 13 cases, by falls in 5 cases, and by falling from height in 4 cases. According to Schatzker classification criteria, 9 cases were type Ⅴ and 13 cases were type Ⅵ. The interval between injury and operation was 5-12 days (mean, 7.9 days). The operation time, intraoperative fluoroscopy times, and length of hospital stay were recorded. The range of motion of knee joint and Hospital for Special Surgery (HSS) score were recorded at last follow-up. X-ray films were taken to review the fracture healing. Rasmussen score, tibial plateau varus angle (TPVA), and posterior tibial slope (PTS) were estimated before operation, at immediate after operation, and at last follow-up in order to evaluate the fracture reduction effect and postoperative outcome. RESULTS: The operation time was 85-140 minutes (mean, 103.9 minutes). Intraoperative fluoroscopy was performed 7-15 times (mean, 10.1 times). All incisions healed by first intention after operation, and no complication such as nerve or blood vessel injury occurred. The length of hospital stay ranged from 8 to 17 days (mean, 12.4 days). All patients were followed up 10-22 months (mean, 14.8 months). At last follow-up, the range of motion of knee joint was 110°-140° (mean, 125°). HSS score was rated as excellent in 16 cases, good in 5 cases, and fair in 1 case, with an excellent and good rate of 95.5%. X-ray films reexamination showed that all fractures healed with the healing time of 12-17 weeks (mean, 14.8 weeks). No internal fixation failure occurred. Rasmussen score, TPVA, and PTS at immediate after operation and at last follow-up were significantly superior to those before operation ( P<0.05). And there was no significant difference between immediately after operation and last follow-up ( P>0.05). CONCLUSION The treatment of Schatzker type Ⅴ and Ⅵ tibial plateau fractures with intermediate screw assisted reduction and fixation technique is reliable, which can reduce the difficulty of reduction and fixation, improve the efficiency of reduction and fixation, reduce the operation time, achieve satisfactory reduction and fixation effect and postoperative prognosis, and achieve good recovery of knee joint function.
Humans ; Tibial Fractures/diagnostic imaging* ; Male ; Female ; Adult ; Middle Aged ; Bone Screws ; Fracture Fixation, Internal/instrumentation* ; Retrospective Studies ; Adolescent ; Aged ; Young Adult ; Treatment Outcome ; Range of Motion, Articular ; Operative Time ; Length of Stay ; Tibial Plateau Fractures

OBJECTIVE: To evaluate the effectiveness of V-shaped stealth decompression technique using ultrasonic bone scalpel in anterior surgery for adjacent two-level cervical spondylosis. METHODS: A clinical data of 41 patients with adjacent two-level cervical spondylosis, who admitted between January 2020 and December 2023 and met the selection criteria, was analyzed retrospectively. Among them, 22 cases were treated with anterior cervical discectomy and fusion (ACDF) assisted by V-shaped stealth decompression technique using ultrasonic bone scalpel (group A) and 19 cases with anterior cervical corpectomy and fusion (ACCF) (group B). There was no significant difference between the two groups in age, gender, disease duration, surgical segment, preoperative Japanese Orthopedic Association (JOA) score, neck dysfunction index (NDI), pain visual analogue scale (VAS) score, and the anteroposterior diameter of the spinal canal in the responsibility space of axial CT ( P>0.05). The operation time, intraoperative blood loss, postoperative drainage volume, hospital stay, complications during follow-up, JOA score, NDI, and VAS score at last follow-up, and the incidences of intervertebral fusion at 3 months after operation, and cage subsidence at last follow-up were compared between the two groups. RESULTS: The operations in the two groups were successfully completed. The operation time, intraoperative blood loss, postoperative drainage volume, and hospital stay in group A were significantly less than those in group B ( P<0.05). Two cases (9.1%) in group A and 4 cases (21.1%) in group B developed complications, with no significant difference in the incidence between the two groups ( P>0.05). All patients in the two groups were followed up 6-12 months (mean, 9.3 months). There was no significant difference in follow-up time between the two groups ( P>0.05). At last follow-up, the JOA score and VAS score in both groups significantly improved when compared with those before operation ( P<0.05). The change values of VAS score and the improvement rate of JOA score in group A were significantly superior to group B ( P<0.05). There was no significant difference in the change values of NDI and JOA score between the two group ( P>0.05). Imaging reexamination showed that the rate of intervertebral fusion at 3 months after operation was significantly higher in group A (81.8%) than in group B (52.6%) ( P<0.05), and all patients obtained bony intervertebral fusion at last follow-up. At last follow-up, 2 cases (9.1%) in group A and 11 cases (57.9%) in group B had cage sinking, and the difference in the incidence was significant ( P<0.05). No loosening or fracture of internal fixators occurred in all patients. CONCLUSION Using ultrasonic bone scalpel can transform single vertebral ACCF into two-segment ACDF in anterior cervical spondylosis surgery. The V-shaped stealth decompression technique is safe and efficient, with the advantages of minimal trauma, fewer postoperative complications, and rapid recovery of patients.
Humans ; Spondylosis/surgery* ; Male ; Female ; Middle Aged ; Decompression, Surgical/instrumentation* ; Retrospective Studies ; Cervical Vertebrae/surgery* ; Spinal Fusion/instrumentation* ; Diskectomy/instrumentation* ; Adult ; Treatment Outcome ; Aged ; Ultrasonic Surgical Procedures/methods* ; Operative Time

Total laryngectomy is a crucial surgical intervention for patients with advanced malignant tumors of the larynx and nasopharynx. Despite its effectiveness, this procedure permanently severs the connection between the nasal cavity and the lower respiratory tract, leading to the cessation of nasal airflow. This disruption significantly impairs the patient's sense of smell and adversely affects their quality of life. Although olfactory loss is common in these patients, the assessment and rehabilitation of their olfactory function are often overlooked. This article reviews relevant literature on evaluating olfactory function and rehabilitation methods following total laryngectomy, with the aim of providing a theoretical foundation to enhance olfactory rehabilitation and overall quality of life for these patients.
Humans ; Laryngectomy/rehabilitation* ; Quality of Life ; Smell ; Laryngeal Neoplasms/surgery* ; Olfaction Disorders/etiology*

Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

The clinical application of antisense oligonucleotide (ASO) therapeutics faces significant challenges, particularly those related to immunogenicity. To address these issues, researchers have introduced chemical modifications to the nucleic acid backbone and terminal structures of ASOs, thereby markedly improving their in vivo stability, target specificity, and resistance to nuclease degradation. In addition, advances in delivery systems and administration strategies have effectively enhanced delivery efficiency, enabling ASOs to better meet diverse therapeutic requirements. This review provides an overview of recent progress in the development, delivery, and immunological aspects of ASOs, with the aim of offering insights into chemical modification, delivery efficiency, and stability, and ultimately promoting the further advancement of ASO therapeutics in disease treatment.