Acute ischemic stroke (AIS) is a kind of central nervous system disease that seriously threatens human health and life. Current treatment for AIS is mainly reperfusion. However, the time-sensitive of reperfusion limits its clinical application, and a considerable part of patients within the time window cannot achieve the expected effect after reperfusion; related complications of reperfusion have not been completely solved. So far, some clinical trials have confirmed that neuroprotectants are useful supplements and adjuncts to reperfusion. This paper reviews the recent advance in neuroprotectants combined with reperfusion in AIS to provide references for AIS treatment.

Hemophilic arthritis(HA),caused by recurrent bleeding,can seriously affect patient quality of life and consumes extensive social and medical resources.There is thus a need to establish an animal model of HA for research;however,this is limited by ethical requirements.Here we review the recent literature and summarize research progress into animal models of HA at home and abroad,from the aspects of species selection,modeling method,histopathology,and imaging evaluation method.Species selection includes rodents such as mice,New Zealand rabbits,beagles,miniature pigs,and crab-eating macaques.Modeling method comprise gene knockout trauma models,gene knockout spontaneous models,and injection models.Among these,the gene knockout spontaneous model closely mimics the pathological process of spontaneous bleeding and concurrent arthritis in human HA,making it more relevant to human HA.However,due to high modeling costs,phenotypic instability,and low survival rates,this model is not the preferred choice for animal experimental studies.In contrast,gene knockout trauma models exhibit characteristics such as short modeling time,strong stability,and high success rates,thus being widely utilized in animal experimental research.Evaluation of HA models involves various imaging method including MRI,micro-CT,MSKUS/PD,in addition to various gross scoring method.By reviewing the progress of HA model research,more experimental evidence is provided for investigating the pathogenesis and validating the efficacy of HA treatments,thereby compensating for the lack of clinical data,particularly in the field of traditional Chinese medicine therapy.

Objective To investigate the dynamic changes and molecular mechanisms of myocardial injury and autophagy as the body's self-protective mechanism at different time points after cerebral ischemia/reperfusion(CI/R).Methods A CI/R model was established in male Sprague-Dawley rats using the Longa thread method.Rats that underwent CI/R following middle cerebral artery occlusion were classified into 6-,12-,24,and 48-hour groups according to the reperfusion time.The concentrations of reactive oxygen species and reac-tive nitrogen species were measured to evaluate myocardial oxidative stress.Cardiomyocyte apoptosis and autophagosomes were observed in the myocardium.Additionally,dynamic changes in myocardial autophagy,autophagic flux,and protein and gene expression of auto-phagy regulators were detected.Results Oxidative-stress-induced injury and apoptosis were observed in the myocardium after CI/R.The number of autophagosomes in cardiomyocytes increased,peaking in the 12 h group,and autophagic flux was impaired during the first 12 h after CI/R.Beclin 1,mammalian target of rapamycin(mTOR),and adenosine monophosphate-activated protein kinase(AMPK)expression levels in the myocardium increased during the first 48 h after CI/R,peaking in the 12 h group.This was consistent with changes in autophagy,which showed significant differences compared with the control group.Conclusion These results indicated that autophagy plays a protective role against CI/R-induced myocardial injury.Furthermore,Beclin 1-mediated autophagy/apoptosis and mTOR-mediated autophagy mutual feedback pathways play important roles in the regulation of autophagy.

Immune Checkpoint Inhibitors ; Transcriptome ; Immunotherapy ; Biomarkers, Tumor

Objective:To explore the clinical effect of laparoscopic anatomical hepatic segment Ⅷ (S8) resection.Methods:Of 16 patients with liver cancer who underwent laparoscopic anatomical hepatic S8 resection at the National Cancer Center from October 2020 to October 2022 were were enrolled, including 13 males and 3 females, aged (59.1±10.9) years. The operation time, intraoperative blood loss, occurrence of intraoperative blood transfusion, and postoperative complications were retrospectively analyzed. Recurrence and survival were followed up by outpatient and telephone reviews.Results:Laparoscopic anatomical hepatic S8 resection was successfully performed in 16 patients without conversion to laparotomy. Among them, 10 patients underwent the intraoperative ultrasound guided hepatic parenchymal approach, and 6 underwent laparoscopic Glissonean pedicle puncture for the positive staining of S8 using indocyanine green. The operation time was (274.8±82.8) min, and the intraoperative blood loss was [ M( Q1, Q3)] 100.0 (50.0, 200.0) ml. There were no intraoperative blood transfusion or postoperative complication. The drainage tube was successfully removed and the patients were discharged 5 to 7 days after surgery. The patients were followed up for 5 to 24 months and all survived. Two patients had tumor recurrence. Conclusion:Laparoscopic anatomical S8 resection is safe and feasible.

OBJECTIVE: To investigate the effects of gene of phosphate and tension homology (PTEN)-induced putative kinase 1 (PINK1)/Parkin pathway on hippocampal mitophagy and cognitive function in mice with sepsis-associated encephalopathy (SAE) and its possible mechanism. METHODS: A total of 80 male C57BL/6J mice were randomly divided into Sham group, cecal ligation puncture (CLP) group, PINK1 plasmid transfection pretreatment groups (p-PINK1+Sham group, p-PINK1+CLP group), empty vector plasmid transfection control group (p-vector+CLP group), with 16 mice in each group. The mice in CLP groups were treated with CLP to reproduce SAE models. The mice in the Sham groups were performed laparotomy only. Animals in the p-PINK1+Sham and p-PINK1+CLP groups were transfected with PINK1 plasmid through the lateral ventricle at 24 hours before surgery, while mice in the p-vector+CLP group were transfected with the empty plasmid. Morris water maze experiment was performed 7 days after CLP. The hippocampal tissues were collected, the pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and the mitochondrial autophagy was observed under a transmission electron microscopy after uranyl acetate and lead citrate staining. The expressions of PINK1, Parkin, Beclin1, interleukins (IL-6, IL-1β) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blotting. RESULTS: Compared with the Sham group, CLP group mice in Morris water maze experiment had longer escape latency, shorter target quadrant residence time, and fewer times of crossing the platform at 1-4 days. Under the light microscope, the hippocampal structure of the mouse was injured, the neuronal cells were arranged in disorder, and the nuclei were pyknotic. Under the electron microscope, the mitochondria appeared swollen, round, and wrapped by bilayer or multilayer membrane structures. Compared with the Sham group, CLP group had higher expressions of PINK1, Parkin, Beclin1, LC3II/LC3I ratio, IL-6 and IL-1β in hippocampus, indicating that sepsis induced by CLP could activated inflammatory response and caused PINK1/Parkin-mediated mitophagy. Compared with the CLP group, p-PINK1+CLP group had shorter escape latencies, spent more time in the target quadrant and had more number of crossings in the target quadrant at 1-4 days. Under the light microscope, the hippocampal structures of mice was destroyed, the neurons were arranged disorderly, and the nuclei were pyknotic. Under transmission electron microscope, swollen and rounded mitochondria and mitochondrial structure wrapped by double membrane or multilayer membrane structure were observed. Compared with the CLP group, the levels of PINK1, Parkin, Beclin1 and LC3II/LC3 ratio in the p-PINK1+CLP group were significantly increased [PINK1 protein (PINK1/β-actin): 1.95±0.17 vs. 1.74±0.15, Parkin protein (Parkin/β-actin): 2.06±0.11 vs. 1.78±0.12, Beclin1 protein (Beclin1/β-actin): 2.11±0.12 vs. 1.67±0.10, LC3II/LC3I ratio: 3.63±0.12 vs. 2.27±0.10, all P < 0.05], while the levels of IL-6 and IL-1β were significantly decreased [IL-6 protein (IL-6/β-actin): 1.69±0.09 vs. 2.00±0.11, IL-1β protein (IL-1β/β-actin): 1.11±0.12 vs. 1.65±0.12, both P < 0.05], suggesting that overexpression of PINK1 protein could further activate mitophagy and reduce the inflammatory response caused by sepsis. There was no statistically significant difference in the above pathological changes and related indicators between Sham group and p-PINK1+Sham group, CLP group and p-vector+CLP group. CONCLUSIONS PINK1 overexpression can further activate CLP-induced mitophagy by upregulating Parkin, thereby inhibiting inflammation response and alleviate cognitive function impairment in SAE mice.
Male ; Animals ; Mice ; Mice, Inbred C57BL ; Sepsis-Associated Encephalopathy ; Phosphates ; Actins ; Beclin-1 ; Interleukin-6 ; Autophagy ; Ubiquitin-Protein Ligases ; Cognitive Dysfunction ; Sepsis ; Mitochondria ; Protein Kinases

Background::Primary cardiac lipoma is very rare, and no consensus has been developed regarding its ideal treatment strategy. This study reviewed the surgical treatment of cardiac lipomas in 20 patients over 20 years.Methods::Twenty patients with cardiac lipomas were treated at Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2002, to January 1, 2022. The patients' clinical data and pathological reports were retrospectively analyzed, and the follow-up with a range of 1 year to 20 years was conducted.Results::The cardiac lipomas were located in the right atrium (RA) or superior vena cava (SVC) in seven patients (35%) (RA in six patients and SVC in one patient), left ventricle in eight patients (40%) (left ventricular chamber in four patients and left ventricular subepicardium and myocardium in four patients), right ventricle in three patients (15%) (right ventricular chamber in one patient and right ventricular subepicardial layer and myocardium in two patients), subepicardial interventricular groove in one patient (5%), and pericardium in one patient (5%). Complete resection was achieved in 14 patients (70%), including seven patients with lipomas in the RA or SVC. Incomplete resection occurred in six patients (30%) with lipomas in the ventricles. No perioperative deaths occurred. Long-term follow-up was conducted for 19 patients (95%), including two (10%) who died. Both patients who died had lipomas incompletely resected due to ventricles involvement, and preoperative malignant arrhythmias persisted post-operatively.Conclusions::The complete resection rate was high, and the long-term prognosis was satisfactory in patients with cardiac lipomas that did not involve the ventricle. The complete resection rate was low in patients with cardiac lipomas in ventricles; and complications, including malignant arrhythmia, were common. Failure of complete resection and post-operative ventricular arrhythmia are correlated with post-operative mortality.

Objective:To investigate the MRI features of fibro-adipose vascular anomaly (FAVA).Methods:The clinical, pathological and MRI data of the FAVA patients confirmed clinically and pathologically in Henan Provincial People’s Hospital from January 2016 to June 2021 were retrospectively analyzed, including 17 females and 13 males, aged 4-53 (18.5±12.8) years.Through the analysis of the MRI images of FAVA performance, including the lesion area, shape, signal, the degree of reinforcement, inner structure, outer structure and other image characteristics, summarize the MRI features.Results:The lesions located at the lower leg (12 cases), thigh (12 cases), upper arm (4 cases), forearm (1 case) and trunk (1 case). Twenty-four case of lower limbs. All cases involved the muscular layer, including 21 cases of superficial muscle layer, 7 cases of deep muscle layer, and 2 cases of both. Twenty-three cases of superficial muscle layer. Most of the affected muscles were quadriceps femoris and gastrocnemius. Morphology: all lesions were intramuscular solid masses growing parallel to the long axis of the muscle. There were 11 cases of focal type, 11 cases of locally infiltrating type, and 8 cases of diffuse type. MRI findings: all lesions showed mixed signal. On T1WI, 28 cases showed cloud-like, band-like and patchy high signal on the background of medium and high signal. On T2WI-FS, all the 30 cases showed low to medium signal areas on the background of high signal, which were dendrimer, ribbon and cloud-like. The lesions showed moderate to obvious heterogeneous progressive enhancement. Twenty-seven lesions had different shapes of vascular shadow, and 28 lesions had drainage vein shadow adjacent to the lesions, 24 of which were located at the proximal end of the lesions. Fascial tail sign was found at the periphery of the lesions in 26 cases, of which 23 cases were located at the upper and lower ends of the lesions.Conclusion:FAVA is a complex vascular malformation with unclear pathological classification. MRI usually shows a solid mass in the superficial muscle layer of the lower limbs parallel to the long axis of the muscle, with cloud-like, band-like, and patchy hyperintensity on the background of high signal on T1WI, and dendritic, band-like, and cloud-like hypointensity on the background of high signal on T2WI-FS, which is helpful for the diagnosis of FAVA. Combined with the data of fascial tail sign, draining vein and clinical manifestations, the diagnosis of FAVA can be confirmed to a certain extent, which can provide reference and basis for clinical decision making.

Objective:To investigate the MRI features of fibro-adipose vascular anomaly (FAVA).Methods:The clinical, pathological and MRI data of the FAVA patients confirmed clinically and pathologically in Henan Provincial People’s Hospital from January 2016 to June 2021 were retrospectively analyzed, including 17 females and 13 males, aged 4-53 (18.5±12.8) years.Through the analysis of the MRI images of FAVA performance, including the lesion area, shape, signal, the degree of reinforcement, inner structure, outer structure and other image characteristics, summarize the MRI features.Results:The lesions located at the lower leg (12 cases), thigh (12 cases), upper arm (4 cases), forearm (1 case) and trunk (1 case). Twenty-four case of lower limbs. All cases involved the muscular layer, including 21 cases of superficial muscle layer, 7 cases of deep muscle layer, and 2 cases of both. Twenty-three cases of superficial muscle layer. Most of the affected muscles were quadriceps femoris and gastrocnemius. Morphology: all lesions were intramuscular solid masses growing parallel to the long axis of the muscle. There were 11 cases of focal type, 11 cases of locally infiltrating type, and 8 cases of diffuse type. MRI findings: all lesions showed mixed signal. On T1WI, 28 cases showed cloud-like, band-like and patchy high signal on the background of medium and high signal. On T2WI-FS, all the 30 cases showed low to medium signal areas on the background of high signal, which were dendrimer, ribbon and cloud-like. The lesions showed moderate to obvious heterogeneous progressive enhancement. Twenty-seven lesions had different shapes of vascular shadow, and 28 lesions had drainage vein shadow adjacent to the lesions, 24 of which were located at the proximal end of the lesions. Fascial tail sign was found at the periphery of the lesions in 26 cases, of which 23 cases were located at the upper and lower ends of the lesions.Conclusion:FAVA is a complex vascular malformation with unclear pathological classification. MRI usually shows a solid mass in the superficial muscle layer of the lower limbs parallel to the long axis of the muscle, with cloud-like, band-like, and patchy hyperintensity on the background of high signal on T1WI, and dendritic, band-like, and cloud-like hypointensity on the background of high signal on T2WI-FS, which is helpful for the diagnosis of FAVA. Combined with the data of fascial tail sign, draining vein and clinical manifestations, the diagnosis of FAVA can be confirmed to a certain extent, which can provide reference and basis for clinical decision making.

Objective:To study the use of the Glissonean pedicle approach based on the triangular area among the right anterior pedicle, the right posterior pedicle and the right hepatic vein ( "APR triangle" ), followed by indocyanine green fluorescence negative staining in laparoscopic anatomical resection of right hepatic segments.Methods:The clinical data of 34 patients with liver tumors who underwent laparoscopic anatomical right hepatic segmentectomy at the Chinese Academy of Medical Sciences and Peking Union Medical College from September 2020 to September 2021 were analyzed retrospectively. Of the 34 patients, there were 24 males and 10 females, aged (58.3±10.3) years old. Data on completion of operation, operation time, intraoperative blood loss, intraoperative blood transfusion, postoperative complications and postoperative hospital stay were collected.Results:All the 34 patients had malignant liver tumors, and they were successfully operated using total laparoscopic surgery. There was no conversion to open surgery. Three patients underwent segment V resection, 3 patients segment VI resection, 5 patients segment VII resection, 2 patients segment V + segment VI resection, 9 patients segment VI + segment VII resection, 3 patients segment V + segment VII resection, 5 patients segment V dorsal segment + segment VI + segment VII resection, 3 patients right posterior section resection + anterior dorsal segment resection and 1 patient anterior dorsal section resection. The operation time was (275.58±82.28) min, the amount of intraoperative blood loss was 100(100, 300) ml, and there were no patients requiring blood transfusion during the operation. Liquid food was started on the first day after operation, and out-of bed activities were carried out on the second to third days after operation. The Clavien Dindo classification of postoperative complications was grade I in 32 patients and grade III in 2 patients. The postoperative hospital stay was (7.23±3.10) d. All tumor margins were negative for malignancy. All the 34 patients were followed-up for (8.94±2.94) months. By the end of follow-up, 34 patients had survived without tumor recurrence.Conclusion:The right Glisson pedicle approach based on the "APR triangle" and the anatomical resection of right hepatic segments with fluorescence negative staining were safe and feasible.