BACKGROUND:Studies have shown that irisin can delay joint degeneration by modulating the metabolic homeostasis of chondrocytes and inhibiting inflammatory responses and oxidative stress.OBJECTIVE:To further explore the mechanism by which irisin exerts therapeutic effects on osteoarthritis.METHODS:(1)Bioinformatics analysis:Gene expression data from cartilage tissues of patients with osteoarthritis and healthy controls were obtained from the GSE51588 and GSE207881 datasets.Gene set variation analysis assessed the activation of programmed cell death in osteoarthritis.Differential expression analysis identified differentially expressed genes between osteoarthritis and control samples,followed by pathway enrichment analysis.Ferroptosis-related differentially expressed genes were further identified,with those having an area under the receiver operating characteristic curve greater than 0.9 designated as core genes.(2)Cell experiment.Human articular chondrocytes were divided into four groups:control(chondrocytes),model(inflammatory models were established in chondrocytes induced by tumor necrosis factor α),model+Erastin(a ferroptosis inducer),and model+Erastin+irisin.ELISA measured glutathione,malondialdehyde and reactive oxygen species levels,while JC-1 assays assessed mitochondrial membrane potential.RT-qPCR quantified mRNA levels of core and ferroptosis-related genes,and western blot analyzed the expression of core genes,ferroptosis-related proteins,ERK pathway components,and apoptotic proteins.RESULTS AND CONCLUSION:(1)Gene set variation analysis indicated significant ferroptosis activation in osteoarthritis.(2)Differential expression analysis highlighted significant enrichment of differentially expressed genes in the ERK signaling pathway.Sixteen ferroptosis-related differentially expressed genes including HMOX1,G6PD,and ALOX5,were identified,all with the area under the curve values above 0.9.(3)In the human articular chondrocytes model+Erastin group,glutathione levels and mitochondrial membrane potential decreased significantly,while malondialdehyde and reactive oxygen species levels increased.The expression of HMOX1,G6PD,ALOX5,glutathione peroxidase 4,and SLC7A11 was significantly downregulated,while p-ERK and Bax levels rose,and Bcl2 decreased(all P＜0.05).Irisin treatment significantly improved ferroptosis-related markers(all P＜0.05).To conclude,HMOX1,G6PD,and ALOX5 may be potential therapeutic targets of osteoarthritis.Irisin offers protective effects in osteoarthritis by modulating ferroptosis-related genes and pathways.

BACKGROUND:Studies have shown that irisin can delay joint degeneration by modulating the metabolic homeostasis of chondrocytes and inhibiting inflammatory responses and oxidative stress.OBJECTIVE:To further explore the mechanism by which irisin exerts therapeutic effects on osteoarthritis.METHODS:(1)Bioinformatics analysis:Gene expression data from cartilage tissues of patients with osteoarthritis and healthy controls were obtained from the GSE51588 and GSE207881 datasets.Gene set variation analysis assessed the activation of programmed cell death in osteoarthritis.Differential expression analysis identified differentially expressed genes between osteoarthritis and control samples,followed by pathway enrichment analysis.Ferroptosis-related differentially expressed genes were further identified,with those having an area under the receiver operating characteristic curve greater than 0.9 designated as core genes.(2)Cell experiment.Human articular chondrocytes were divided into four groups:control(chondrocytes),model(inflammatory models were established in chondrocytes induced by tumor necrosis factor α),model+Erastin(a ferroptosis inducer),and model+Erastin+irisin.ELISA measured glutathione,malondialdehyde and reactive oxygen species levels,while JC-1 assays assessed mitochondrial membrane potential.RT-qPCR quantified mRNA levels of core and ferroptosis-related genes,and western blot analyzed the expression of core genes,ferroptosis-related proteins,ERK pathway components,and apoptotic proteins.RESULTS AND CONCLUSION:(1)Gene set variation analysis indicated significant ferroptosis activation in osteoarthritis.(2)Differential expression analysis highlighted significant enrichment of differentially expressed genes in the ERK signaling pathway.Sixteen ferroptosis-related differentially expressed genes including HMOX1,G6PD,and ALOX5,were identified,all with the area under the curve values above 0.9.(3)In the human articular chondrocytes model+Erastin group,glutathione levels and mitochondrial membrane potential decreased significantly,while malondialdehyde and reactive oxygen species levels increased.The expression of HMOX1,G6PD,ALOX5,glutathione peroxidase 4,and SLC7A11 was significantly downregulated,while p-ERK and Bax levels rose,and Bcl2 decreased(all P＜0.05).Irisin treatment significantly improved ferroptosis-related markers(all P＜0.05).To conclude,HMOX1,G6PD,and ALOX5 may be potential therapeutic targets of osteoarthritis.Irisin offers protective effects in osteoarthritis by modulating ferroptosis-related genes and pathways.

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.

This study aimed to identify mutations in the human insulin receptor gene (INSR) and investigate their role in the pathogenesis of severe insulin resistance syndrome. Sanger sequencing of the INSR gene was performed on a patient clinically suspected of having type A insulin resistance syndrome admitted to the Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital. Upon identifying mutations, relevant exons were sequenced in her first-degree relatives. Additionally, control groups consisting of individuals with type 2 diabetes and those with normal glucose tolerance were screened for the mutation detected in the patient. Functional predictions of the INSR protein were made using MutationTaster, SIFT, and PolyPhen2 software. A previously unreported heterozygous missense mutation, c.3652G/A (Asp1218Asn), in exon 20 was identified in both the proband and her father. This mutation was not present in any of the control individuals. Multiple prediction tools indicate that this mutation likely disrupts gene/protein structure or function. The c.3652G/A (Asp1218Asn) heterozygous mutation in INSR is a novel variant that plays a significant role in the pathogenesis of severe insulin resistance in this Chinese family.

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.

This study aimed to identify mutations in the human insulin receptor gene (INSR) and investigate their role in the pathogenesis of severe insulin resistance syndrome. Sanger sequencing of the INSR gene was performed on a patient clinically suspected of having type A insulin resistance syndrome admitted to the Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital. Upon identifying mutations, relevant exons were sequenced in her first-degree relatives. Additionally, control groups consisting of individuals with type 2 diabetes and those with normal glucose tolerance were screened for the mutation detected in the patient. Functional predictions of the INSR protein were made using MutationTaster, SIFT, and PolyPhen2 software. A previously unreported heterozygous missense mutation, c.3652G/A (Asp1218Asn), in exon 20 was identified in both the proband and her father. This mutation was not present in any of the control individuals. Multiple prediction tools indicate that this mutation likely disrupts gene/protein structure or function. The c.3652G/A (Asp1218Asn) heterozygous mutation in INSR is a novel variant that plays a significant role in the pathogenesis of severe insulin resistance in this Chinese family.

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.

Due to traditional professional divisions, the practice of endoscopy by gastro-intestinal surgeons in China remains controversial. However, with the evolution of treatment philo-sophies, medical technology, and equipment advancements, a trend of integration between tradi-tional surgery and endoscopy is emerging. Gastrointestinal surgeons performing endoscopy can maxi-mize patient benefits, and they naturally possess advantages in conducting endoscopic procedures. It is recommended to further establish entry thresholds for surgeons to perform endoscopy, provide standardized endoscopic training for surgeons, and coordinate efforts at the administrative depart-ment. With the support of artificial intelligence, more patients can receive minimally invasive, indivi-dualized, and precise treatments.

Lymphocytic hypophysitis(LYH) is a rare autoimmune disease, which is more common in women and is closely associated with pregnancy. For patients with lymphocytic hypophysitis, the clinical manifestations mainly depend on the speed of disease progression, the extent of lesions, the severity and stage of disease, which can present as mass effect, decreased anterior pituitary hormone function, and central diabetes insipidus, etc. Due to physical changes in pituitary anatomy and hormone levels, as well as restriction of imaging examinations during pregnancy, it poses greater challenge to establish diagnosis in perinatal patients, which demands a comprehensive assessment of the patient′s clinical symptoms and biochemical tests. For treatment, patients with hypopituitarism during pregnancy should be given hormone replacement therapy. Moreover, patients need to adopt optimized tailored therapy according to gestational age and various clinical manifestations. At present, there is no report on the adverse effects of LYH on pregnancy outcome and re-pregnancy. This review discusses the diagnosis, treatment and prognosis of patients with LYH during pregnancy, and provides reference for the clinical management of this condition.

Objective:To explore the effect and mechanism of dendritic cell derived exosomes (Dexs) loading ubiquitinated (Ub) hepatitis D antigen (HDAg) on activating specific cytotoxic T lymphocytes (CTL).Methods:Ub-S-HDAg-Dexs were co-cultured with dendritic cells (DC) which were from the femora of C57BL/6 mice for 48 h, then flow cytometry was used to detect the maturity of DC (CD86, CD80 and major histocompatibility complex (MHC) Ⅱ). The spleen-derived T lymphocytes from C57BL/6 mice were added in vitro to activate DC and co-cultivated for 72 h. The T cells were divided into Ub-S-HDAg-Dexs group (add 50 μg/mL Ub-S-HDAg-Dexs), Blank-Dexs group (add 50 μg/mL DC derived exosomes without plasmid transfection), Con-Dexs group (add 50 μg/mL DC derived exosomes transfected by cantrol plasmid), PBS group (add 50 μL/mL phosphate buffered saline), and Ub-S-HDAg-Dexs+ AG490 group (add 50 μg/mL Ub-S-HDAg-Dexs, DC and T lymphocytes stimulated by exosomes, and 50 μmol/L AG490 was also added to the cell mix). Flow cytometry was used to detect CD8 + T cells secreting interferon-gamma, non-radioactive lactate dehydrogenase release test to detect the killing activity of specific CTL. Real-time quantitative polymerase chain reaction (PCR) and Western blotting were used to detect the mRNA and protein expressions of JAK kinase (JAK) 2, GATA-binding protein 3 (GATA3), T-bet, signal transduction and activator of transcription (STAT) 1 and STAT4. Independent sample t test were used for statistical analysis. Results:The positive rates of the surface molecules CD80, CD86, MHCⅡof DC stimulated by Ub-S-HDAg-Dexs were 83.850%±0.219%、68.910%±0.134%、84.320%±0.445%, respectively.In the Ub-S-HDAg-Dexs group, the rate of CD8 + T cells secreting interferon-gamma was 6.420%±0.028%, which was higher than those of other groups, including PBS group, Blank-Dexs group, Con-Dexs group and Ub-S-HDAg-Dexs+ AG490 group ( t=90.78, 30.32, 63.06 and 85.42, respectively, all P<0.001). The cytotoxicity of T cells in the Ub-S-HDAg-Dexs group was 82.4%±3.9%, which was higher than those of other groups ( t=17.28, 9.74, 3.95 and 15.89, respectively, all P<0.050). The relative mRNA expressions of JAK2, T-bet, STAT1, STAT4 in Ub-S-HDAg-Dexs group were higher than those in other groups, including Con-Dexs group ( t=10.74, 32.34, 13.00 and 16.28, respectively, all P<0.001), Blank-Dexs group ( t=15.05, 21.51, 6.46 and 13.12, respectively, all P<0.050), PBS group ( t=21.83, 41.42, 7.30 and 17.50, respectively, all P<0.050), Ub-S-HDAg-Dexs+ AG490 group ( t=35.75, 20.69, 17.02 and 17.07, respectively, all P<0.001), and the differences were all statistically significant. The protein expressions of T-bet, STAT1, STAT4 in Ub-S-HDAg-Dexs group increased compared with those in PBS group ( t=346.70, 57.54 and 55.81, respectively, all P<0.001), with statistical significance. In the presence of AG490, the protein expressions of T-bet, STAT1 and STAT4 decreased compared with those in Ub-S-HDAg-Dexs group, and the differences were statistically significant ( t=355.40, 52.79 and 126.10, respectively, all P<0.001). Conclusions:Ubiquitinated HDAg transported by exosomes could effectively promote DC maturation, induce T lymphocyte differentiation, and generate specific CTL responses, which provides a new idea for the treatment of hepatitis D.