Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

BACKGROUND:Studies have shown that cardiomyocyte apoptosis is closely related to cardiac decompensation and the cardiac aging process.Appropriate exercise can alter heart pump function in patients with heart failure as well as attenuate aging-induced cardiomyocyte apoptosis,hypertrophy,and fibrotic damage. OBJECTIVE:To investigate the effects of long-term aerobic exercise on cardiomyocyte apoptosis and the thioredoxin system in aging rats. METHODS:Thirty-six male Sprague-Dawley rats were selected and divided into three age groups:3-month-old young group,9-month-old middle-aged group,and 18-month-old elderly group,with 12 rats in each group.Within each age group,rats were randomly assigned to sedentary and exercise subgroups(n=6 per group).The sedentary groups did not undergo any exercise intervention.The exercise groups were acclimated to a treadmill environment and subsequently subjected to treadmill exercise for 45 minutes per day,at a speed of 15 m/min,5 days per week for 10 weeks in total.At 24 hours after the final intervention,ELISA was employed to measure serum levels of cardiac troponin I and creatine kinase-MB in rats.TUNEL assay was utilized to detect cardiomyocyte apoptosis,while western blot assay was employed to assess the protein expression of Bax,Bcl-2,Caspase 3,thioredoxin-1,thioredoxin-2,thioredoxin reductase-1,thioredoxin reductase-2,thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardial tissue. RESULTS AND CONCLUSION:Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged sedentary groups and elderly exercise group(P<0.01).Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged exercise groups and elderly exercise group(P<0.01).Positive apoptotic cells in rat myocardial tissue,along with increased protein expression of Bax and Caspase 3,exhibited an age-related upward trend,while Bcl-2 protein expression showed a declining trend.In comparison with the sedentary groups within each age category,the number of apoptotic cardiomyocytes and the expression of Bax and Caspase 3 proteins were reduced to different degrees,and the expression of Bcl-2 protein was increased to different degrees in the corresponding exercise groups.Compared with the young sedentary group,middle-aged sedentary group and elderly exercise group,elderly sedentary rats showed a significant decrease in the expression of myocardial thioredoxin 1,thioredoxin 2,thioredoxin reductase 1,and thioredoxin reductase 2 proteins(P<0.05,P<0.01).The expression of myocardial thioredoxin 1,thioredoxin 2,and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the young exercise group(P<0.05,P<0.01),while the expression of thioredoxin reductase 1 and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the middle-aged exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly sedentary group than the young sedentary group,middle-aged sedentary group and elderly exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly exercise group than the young exercise group and middle-aged exercise group(P<0.01).To conclude,aerobic exercise may enhance the anti-apoptotic effects of thioredoxin by down-regulating the expression of thioredoxin-interacting protein in aging rat hearts,leading to the downregulation of apoptosis signal-regulated kinase 1 and P38 mitogen-activated kinase protein,thereby alleviating myocardial cell apoptosis in aging rat hearts.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective To investigate the impact of total parathyroidectomy with autotransplantation (tPTx+AT)on bone mineral density and serum soluble Klotho (sKlotho)level in patients with secondary hyperparathyroidism (SHPT).Methods A total of 86 patients undergoing tPTx+AT in the Second Affiliated Hospital of Anhui Medical University from June 2019 to May 2022 were recruited in this study.Their demographic characteristics were collected before surgery,along with serum levels of corrected calcium,phosphorus,intact parathyroid hormone (iPTH),alkaline phosphatase (ALP),fibroblast growth factor 23 (FGF23),and sKlotho before and at 5 d,and 1,3,6,12 and 24 months after surgery.Dual energy X-ray absorptiometry was used to determine the BMD values of the lumbar spine L1-L4 before surgery and at 3,6,12 and 24 months after surgery.The changes in BMD and serum FGF23 and sKlotho levels before and after tPTx+AT were observed.Results Surgical treatment was successfully completed in all 86 patients,with their clinical symptoms such as bone pain and skin itching significantly improved postoperatively,and markedly decreased serum calcium,phosphorus,iPTH,ALP and FGF23 levels.The sKlotho level was significantly lower at 5 d postoperatively than that preoperatively,with that at 1 month after surgery increased by approximately 24.5％ than the preoperative level,and then the level was in a stable trend.The BMD values at the lumbar spine L1-L4 were increased postoperatively,and reached the highest levels at 12 months postoperatively.Further analyses showed that dialysis vintage,duration of SHPT,and ALP,iPTH and FGF23 levels were negatively correlated with the Z-scores of the lumbar spine L1-L4,while sKlotho level was positively correlated with the Z-scores.Conclusion tPTx+Atcan significantly improve the clinical symptoms of SHPT patients,regulate the balance of calcium and phosphorus metabolism,increase sKlotho level and reduce FGF23 level.It is an effective method to improve BMD.

Objectives:This study aims to explore the clinical significance of lateral pelvic sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence navigation in laparoscopic lateral pelvic lymph node dissection (LLND) and evaluate the accuracy and feasibility of this technique to predict the status of lateral pelvic lymph nodes (LPLNs).Methods:The clinical and pathological characteristics, surgical outcomes, lymph node findings and perioperative complications of 16 rectal cancer patients who underwent SLNB using ICG fluorescence navigation in laparoscopic LLND in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during April 2017 and October 2022 were retrospectively collected and analyzed. The patients did not receive preoperative neoadjuvant radiotherapy and presented with LPLNs but without LPLN enlargement (MRI showed the maximum short axes of the LPLNs were ≥5 mm and <10 mm at first visit).Results:All 16 patients were successfully performed SLNB using ICG fluorescence navigation in laparoscopic LLND. Three patients underwent bilateral LLND and 13 patients underwent unilateral LLND. The lateral pelvic sentinel lymph nodes (SLNs) were clearly fluorescent before dissection in 14 patients and the detection rate of SLNs for these patients was 87.5%. Lateral pelvic SLN metastasis was diagnosed in 2 patients and negative results were found in 12 patients by frozen pathological examinations. Among the 14 patients in whom lateral pelvic SLNs were detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLNs. The specificity, sensitivity, negative predictive value, and accuracy was 85.7%, 100%, 100%, and 100%, respectively.Conclusions:This study indicates that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure with good accuracy. This technique may replace preventive LLND for locally advanced lower rectal cancer.

Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9％NaCl),model group(intraperitoneal injection of 40％CC14 peanut oil solution induced HF model,intragastric administration of 0.9％NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.

Objectives:This study aims to explore the clinical significance of lateral pelvic sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence navigation in laparoscopic lateral pelvic lymph node dissection (LLND) and evaluate the accuracy and feasibility of this technique to predict the status of lateral pelvic lymph nodes (LPLNs).Methods:The clinical and pathological characteristics, surgical outcomes, lymph node findings and perioperative complications of 16 rectal cancer patients who underwent SLNB using ICG fluorescence navigation in laparoscopic LLND in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during April 2017 and October 2022 were retrospectively collected and analyzed. The patients did not receive preoperative neoadjuvant radiotherapy and presented with LPLNs but without LPLN enlargement (MRI showed the maximum short axes of the LPLNs were ≥5 mm and <10 mm at first visit).Results:All 16 patients were successfully performed SLNB using ICG fluorescence navigation in laparoscopic LLND. Three patients underwent bilateral LLND and 13 patients underwent unilateral LLND. The lateral pelvic sentinel lymph nodes (SLNs) were clearly fluorescent before dissection in 14 patients and the detection rate of SLNs for these patients was 87.5%. Lateral pelvic SLN metastasis was diagnosed in 2 patients and negative results were found in 12 patients by frozen pathological examinations. Among the 14 patients in whom lateral pelvic SLNs were detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLNs. The specificity, sensitivity, negative predictive value, and accuracy was 85.7%, 100%, 100%, and 100%, respectively.Conclusions:This study indicates that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure with good accuracy. This technique may replace preventive LLND for locally advanced lower rectal cancer.

Objective To investigate the correlations of serum cell division cycle 42 (CDC-42), β₂-microglobulin (β₂-MG) and fibulin 1 (FBLN1) levels with abdominal aortic calcification (AAC) in patients with maintenance hemodialysis (MHD). Methods General information and biochemical indicators of 74 MHD patients were collected, and they were divided into no to mild AAC group (n=36) and moderate to severe AAC group (n=38) based on the Abdominal Aortic Calcification Score (AACs). Serum levels of CDC-42, β₂-MG and FBLN1 were compared between the two groups, and multivariate Logistic regression analysis was used to explore the risk factors for AAC in MHD patients. Results The dialysis vintage, serum phosphorus, intact parathyroid hormone (iPTH), CDC-42, β₂-MG and FBLN1 levels in the moderate to severe AAC group were significantly higher than those in the no to mild AAC group (P < 0.05). AAC in MHD patients was positively correlated with serum phosphorus, iPTH, CDC-42, β₂-MG, FBLN1, and dialysis vintage (P < 0.05). High levels of CDC-42, β₂-MG and FBLN1 as well as long dialysis vintage were independent risk factors for AAC in MHD patients (P < 0.05). Conclusion Serum CDC-42, β₂-MG and FBLN1 levels are positively correlated with AAC in MHD patients. High levels of CDC-42, β₂-MG and FBLN1 as well as long dialysis vintage are independent risk factors for AAC in MHD patients.

Humans ; Multiple Myeloma/drug therapy* ; Feasibility Studies ; Antibodies, Monoclonal/adverse effects* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols