Uveal melanoma(UM)is the most common primary intraocular malignancy in adults and arises predominantly from the choroid. Mitochondria, as essential organelles, not only fuel energy metabolism, but also orchestrate signal transduction and apoptosis. Recent studies have progressively uncovered the multifaceted roles of mitochondria in UM, including mitochondrial DNA copy-number alterations, reprogramming of mitochondria-related metabolic genes, and mitochondria-dependent autophagy. Moreover, mitochondria modulate UM progression partly through the PI3K/AKT axis. Natural compounds and small-molecule drugs that impair mitochondrial function have also shown promising activity in inducing UM cell dysfunction. These findings provide new insights into UM pathogenesis and highlight mitochondria as potential therapeutic targets.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To analyze the clinical efficacy of pasteurization-inactivated tumor bone replantation combined with intramedullary vascularized fibula for reconstructing bone defects after surgery for malignant bone tumors in children and adolescents.Methods:A retrospective analysis was performed on the data of 54 patients who underwent pasteurization-inactivated tumor bone replantation combined with intramedullary vascularized fibula reconstruction for bone defects after surgery for malignant bone tumors at the Bone and Soft Tissue Tumor Treatment Center of Peking University People's Hospital from September 2015 to September 2023. There were 39 males and 15 females, with an age of 12.4±5.6 years (range, 4 to 23 years). The tumor types included 33 cases of osteosarcoma, 19 cases of Ewing sarcoma, and 2 cases of soft tissue sarcoma. All cases were at Enneking stage IIB. The tumor locations were 30 cases in the femur, 19 cases in the tibia, 4 cases in the ilium, and 1 case in the humerus. The survival rate, bone healing time, tumor recurrence, and metastasis were observed. The limb function was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 score.Results:All patients successfully completed the surgery and were followed up, with a follow-up time of 44.6±27.1 months (range, 12 to 96 months). The operation time was 527±132 min (range, 150 to 730 min), and the blood loss was 730±591 ml (range, 300 to 2,800 ml). The length of inactivated tumor bone was 16.5±4.5 cm (range, 9.1 to 24.0 cm), the defect length accounted for 43.4%±12.2% of the total length of the affected bone (range, 23.8% to 75.5%), the proximal osteotomy of the long bones in the extremities was 14.1±8.3 cm from the articular surface (range, 1.9 to 31.1 cm), the distal osteotomy was 9.4±6.2 cm from the articular surface (range, 1.7 to 22.9 cm), and the length of the harvested vascularized fibula was 18.0±4.0 cm (range, 11.0 to 26.4 cm). At the last follow-up, 51 patients were alive, including 47 with no evidence of tumor and 4 with tumor; 3 patients died of tumor progression. Local recurrence occurred in 5 patients, including 4 with soft tissue recurrence in the surgical area (3 underwent surgical resection and 1 received radiotherapy) and 1 with recurrence at the site of inactivated bone. Distant metastasis occurred in 11 patients, including 5 with lung metastasis only, 2 with bone metastasis only, and 4 with combined lung and bone metastasis. Among the 5 patients with lung metastasis only, lung metastases were resected, with 3 surviving with tumor, 2 surviving without tumor; the 2 patients with bone metastasis only underwent surgical resection of bone metastases, both surviving without tumor. Among the 4 patients with combined lung and bone metastasis, 3 died of tumor progression and 1 survived with tumor. The Kaplan-Meier curve showed a 5-year survival rate of 90.8%±6.2% and a 5-year recurrence-free and metastasis-free survival rate of 68.7%±7.9%. The osteotomy healing time at the diaphysis was 8.4±2.3 months (range, 4 to 13 months), the osteotomy healing time at the metaphysis was 5.9±1.7 months (range, 3 to 10 months), and the healing time between inactivated tumor bone and fibula was 6.4±2.0 months (range, 4 to 11 months). No nonunion occurred. The MSTS-93 score at the last follow-up was 94.4%±4.8% (range, 80% to 100%).Conclusion:Pasteurization-inactivated tumor bone replantation combined with intramedullary vascularized fibula reconstruction for bone defects after surgery for malignant bone tumors in children and adolescents has satisfactory clinical efficacy, high bone healing rate, and low rates of local recurrence and distant metastasis.

Objective:To evaluate the preliminary clinical efficacy of minimally invasive extendable prostheses in limb-salvage treatment for distal femoral osteosarcoma in children.Methods:A retrospective analysis was conducted on 36 children who underwent reconstruction of bone defects after distal femoral osteosarcoma resection with minimally invasive extendable prostheses at Peking University People's Hospital between December 2021 and December 2023. The cohort included 22 males and 14 females, with a mean age of 10.1±2.7 years (range: 4.3-14.3 years). Among them, 27 cases were primary tumor resections with post-resection bone defects of 17.4±3.2 cm (range: 13.5-25.0 cm), and 9 cases were revision surgeries. Preoperatively, femoral limb length discrepancy (LLD) was 29.6±14.3 mm (range: -1.2-55.0 mm), tibial LLD was 16.0±11.3 mm (range: -4.8-30.0 mm), and total lower limb LLD was 45.1±23.6 mm (range: -5.5-77.0 mm). The prosthesis was modular and compatible with existing tumor prosthesis components via taper connections. Lengthening was achieved by axial screw manual expansion through a 3-4 cm parapatellar arc incision, using a specialized wrench for adjustment. X-rays were performed pre-implantation, before and after each lengthening, and at the last follow-up to assess femoral, tibial, and total lower limb LLD, as well as extension length. At the final follow-up, limb function was assessed using the Musculoskeletal Tumor Society (MSTS)-93 score, and extension-related complications were analyzed.Results:All 36 children successfully underwent implantation and subsequent extension when indicated. The mean follow-up was 14.9±8.1 months (range: 6-31 months). Eleven patients underwent 16 lengthening procedures, with a mean of 1.5±0.8 per case (range: 1-3) and an average extension of 21.1±8.3 mm (range: 9.2-42.8 mm), achieving a total mean recovery of 31.0±16.1 mm (range: 10.4-61.7 mm). Two patients reached the maximum 5 cm extension capacity and underwent minor procedures to retract the extension device and secure the prosthesis. The remaining 25 patients did not require extension as their LLD was <2 cm. At the last follow-up, femoral, tibial, and total lower limb LLDs were 10.6±11.4 mm (range: -8.6-41.4 mm), 9.1±12.7 mm (range: -9.5-39.5 mm), and 20.1±21.0 mm (range: -10.4-72.5 mm), respectively. The mean MSTS-93 score for the 11 extended patients was 90.0%±12.7% (range: 80.0%-96.7%). Complications included two cases of aseptic loosening requiring revision, one transient peroneal nerve palsy after fixed-length filling, and three cases of prosthesis segment retraction due to excessive exercise. Retractions occurred at 9.1±3.3 months (range: 5.3-11.3 months) and were corrected during subsequent extensions without revision.Conclusions:Minimally invasive extendable prostheses allow individualized limb lengthening through small parapatellar incisions based on LLD and soft tissue tension. The extension mechanism is stable, and functional recovery is favorable.

Objective To investigate the effects of liraglutide on the gut microbiota of db/db diabetic mice and the predictive value of the microbial structure for the hypoglycemic efficacy.Methods The db/db mice were randomly divided into control group and liraglutide group(0.4 μg/g).Fasting blood glucose levels were measured in the mice,and fecal samples were collected to determine the structure of the gut microbiota.Results Compared with the control group,the liraglutide group exhibi-ted a significant increase in the average number of operational taxonomic unit(OTU)(P＜0.01).The number of observed species,Chao1 index and ACE index were all significantly higher in the liraglutide group than those in the control group(P＜0.05).Additionally,the liraglutide group showed a signifi-cant increase in the relative abundance of Firmicutes and a significant decrease in the abundance of Actinobacteria compared with the control group(P＜0.01).The percentage decrease in blood glucose levels in db/db mice was positively correlated with the abundance of Pseudomonadaceae and negatively correlated with the abundances of Clostridiaceae and Peptostreptococcaceae.Conclusion Liraglutide treatment can modulate the structure of the gut microbiota,increasing the number of OTU and diversity,particularly enhancing the abundance of beneficial bacteria such as Clostridium,Lachnospira and Oscillospira.The gut microbiota structure in mice serves as a predictive factor for the hypoglycemic efficacy of liraglutide,with diabetic mice exhibiting a higher abundance of Pseudomonas being more likely to benefit from liraglutide-induced hypoglycemic therapy.

Objective To explore the application value of microwave ablation under ultrasound-magnetic resonance imaging(US-MRI)in the treatment of small liver cancer.Methods A total of 94 patients with small liver cancer were selected and randomly divided into observation group and control group using a random number table method,with 47 patients in each group.The observation group underwent microwave ablation under US-MRI,while the control group received surgical resection.The tumor control rate,periopera-tive indicators,liver function indicators[total bilirubin(TBIL),albumin(ALB),aspartate aminotransferase(AST),and alanine amin-otransferase(ALT)],postoperative complications,and 6-month follow-up status were compared between the two groups.Results There was no significant difference in tumor control rate between the two groups(P>0.05).In the observation group,the proportion of patients with smaller intraoperative blood loss,shorter operative time and postoperative performance status(PS)score of 0-1 was higher than those in the control group(P<0.05).After treatment,the levels of TBIL,AST and ALT were lower and the level of ALB was higher,and the incidence of complications was lower in the observation group(P<0.05).There were no significant differences between the two groups in residual lesion and recurrence(P>0.05).Conclusion The short-term efficacy of microwave ablation under US-MRI in the treatment of small liver cancer is similar to that of surgical treatment,and the microwave ablation under US-MRI can also reduce liver function injury,reduce intraoperative blood loss and shorten operation time.

Objective:To analyze the clinicopathological characteristics and prognostic factors of patients with Castleman disease (CD).Methods:A retrospective case-series study was conducted. A total of 85 patients newly diagnosed with CD in the First Affiliated Hospital of Air Force Medical University between July 2007 and August 2024 were collected. Their clinical characteristics and prognostic factors were analyzed.Results:Among the 85 patients, 45 had unicentric Castleman disease (UCD) and 40 had multicentric Castleman disease (MCD). In the UCD group, females were more commonly affected (64.4%, 29/45), with a median age of onset of 39 years. The primary lesions were mainly located in the retroperitoneum, neck, abdomen, and axilla; and the hyaline vascular subtype was the predominant pathological type (69.4%, 25/36). In the MCD group, males were more frequently affected (62.5%, 25/40), with a median age of onset of 50 years; and the plasmacytic subtype was the main pathological type (68.2%, 15/22). Compared with UCD patients, MCD patients presented more systemic symptoms and signs [85.0% (34/40) vs. 13.3% (6/45), χ2 = 43.66, P < 0.001], splenomegaly [42.5% (17/40) vs. 2.2% (1/45), χ2 = 20.58, P < 0.001], hepatomegaly [25.0% (10/40) vs. 0 (0/45), χ2 = 10.46, P = 0.001], edema or effusion in serous cavity [67.5% (27/40) vs. 8.9%(4/45), χ2 = 31.40, P < 0.001], hematological system involvement [32.5% (13/40) vs. 0 (0/44), χ2 = 16.92, P < 0.001], and renal involvement [22.5% (9/40) vs. 2.3%(1/44), χ2 = 6.36, P = 0.012]. Laboratory findings showed that the levels of hemoglobin and albumin in MCD patients were lower than those in UCD patients, while white blood cell count in MCD patients was higher than that in UCD patients. Additionally, MCD patients exhibited elevated levels of C-reactive protein, interleukin-6, vascular endothelial growth factor, erythrocyte sedimentation rate, and ferritin compared to UCD patients (all P < 0.05). Among UCD patients, 40 cases underwent simple surgical resection, with no deaths during follow-up and the 5-year overall survival (OS) rate of 100.0%; among MCD patients, 34 cases received chemotherapy, 4 received siltuximab, 3 died during follow-up with a 5-year OS rate of 87.5%; and there was no statistically significant difference in OS between the MCD and UCD groups ( χ2 = 3.67, P = 0.055). Among MCD patients, the OS of those with renal involvement (9 cases) was worse than that of those without renal involvement (31 cases) ( χ2 = 8.39, P = 0.004). Conclusions:CD is a highly heterogeneous disorder. Surgical resection is the primary treatment for UCD, with a favorable prognosis. Chemotherapy is the main treatment for MCD, with a relatively poor prognosis.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks