Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 µg/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 µg/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

Objective:Using ultrasound imaging technology to evaluate the contraction characteristics of diaphragm in patients with chronic low back pain.Methods:Twenty nine patients with chronic low back pain and 26 healthy persons recruited from the rehabilitation department of the Third Affiliated Hospital of Sun Yat-sen University from November 2019 to April 2020 were selected and divided into the low back pain (LBP) group and the healthy control group. The thickness of the diaphragm (Tdi) of the subjects during deep breathing was evaluated by portable color Doppler ultrasound equipment under different body positions. The subjects were required to perform maximum inspiration for total lung capacity (TLC) and expiration for functional residual capacity (FRC) in the supine and standing position, respectively. The end-inspiratory diaphragm thickness (TdiTLC) and end-expiratory diaphragm thickness (TdiFRC) were recorded, and the diaphragmatic thickening fraction (DTF) was calculated. The general data of subjects with lower back pain and the correlation between Oswestry Dysfunction Index (ODI) and diaphragm function were analyzed; The diaphragm function of healthy control group and LBP group were compared; The receiver operating characteristic (ROC) curve of Tdi and DTF in the diagnosis of lower back pain were analyzed.Results:ODI lifting score was negatively correlated with standing TdiTLC ( r=-0.50, P<0.01). In intra-group comparison, the TdiTLC and TdiFRC values of healthy subjects in standing position were increased compared with those in supine position ( t=6.115, 7.314, all P<0.001); In standing position, TdiTCL and TdiFRC values in LBP group were increased compared with those in supine position ( t=2.834, 4.673, all P<0.01). In comparison between groups, TdiTLC values in supine and standing position of LBP group were significantly lower than those in healthy control group ( t=2.597, 3.338, all P<0.05); In standing position, TdiFRC of patients in LBP group was significantly lower than that of healthy control group ( t=2.098, P=0.041) and DTF value of patients in LBP group was significantly lower than that of healthy control group ( t=2.902, P=0.006). When TdiTCL≤3.3 mm in supine position was used to predict low back pain, the diagnostic sensitivity and specificity were 78.6% and 53.8%, respectively, and the area under the curve was 0.661. When TdiTCL≤4.5 mm in standing position was used to predict low back pain, the diagnostic sensitivity and specificity were 95.7% and 46.2%, respectively, and the area under the curve was 0.759. When DTF≤81.3% in standing position was used to predict low back pain, the diagnostic sensitivity and specificity were 52.2% and 84.6%, respectively, and the area under the curve was 0.698. Conclusions:It is found in our study that the diaphragm contractile function of patients with lower back pain is worse than that of normal subjects, and the difference was significant in standing position. We suggest that the right-side ultrasound image acquisition in the patient′s standing position is helpful to ensure the accuracy and objectivity of the measurement results. TdiTCL≤4.5 mm or DTF≤81.3% in standing position can be used as one of the reference indexes for the combined diagnosis of chronic low back pain.

OBJECTIVE：To explore high-alert drug management mode of our hospital ，and to provide reference for the management and utilization of this category in medical institutions. METHODS ：According to High-alert Drug Catalog （2019 edition）issued by Hospital Pharmacy Committee of Chinese Pharmaceutical Association ，the high-alert drug catalog of our hospital and their risk points were formulated. Relevant training and assessment were conducted for physicians ，pharmacists and nurses throughout the hospital. Using qualification rate of high-alert drug management and utilization as index ，the effectiveness of high-alert drug management and utilization were compared before and after optimization. RESULTS ：In our hospital ，the risk of high-alert drugs was controlled by establishing inspection and supervision group ，pharmacist education ，information management ， prescription review and individualized administration ，medication guidance ，prescription review and medication error reporting and other measures and with continuous optimization. Compared with before optimization ，qulification rate of high-alert drug management and utilization increased from 37.3％ to 80.1％ in clinical departments （P＜0.01），and that increased from 59.2％ to 85.0％ in pharmacy department （P＜0.01）. There were still some problems ，such as the inconsistency of high-alert drugs accounts and materials ，the failure to report all medication errors in time ，the imperfect establishment of prescription review software rules ， the insufficient medication guidance ，and the lack of individual medication varieties. CONCLUSIONS ：By optimizing the management of high-alert drugs ，the management and utlization of this category is improved effectively in clinical departments and pharmacy departments of our hospital.

Objective: To retrospectively analyze the efficacy and prognostic factors of postoperative intensity modulated radiotherapy for grade Ⅱ gliomas. Methods: Retrospective analysis was conducted on patients with postoperative grade Ⅱ glioma in our hospital from Jan. 2010 to Dec. 2018. The primary endpoint was progression-free survival, and the secondary endpoint was overall survival. Correlative analyses of prognosis by age, gender, initial resection status, the maximum diameter of the lesions, bi-hemisphere, astrocytoma, chemoradiation, adjuvant chemotherapy were conducted. Results: A total of 109 cases with grade Ⅱ glioma were enrolled. The follow-up rate was 91.75%, including 10 cases dead and 27 relapsed. There were 24 cases (88.9%) of in-field failure, and 3 cases (11.1%) of out-field failure. 14 cases of recurrence occurred in 81 cases of total resection group, accounting for 17.3%, and 13 in 28 cases of subtotal resection group, accounting for 46.4%. The recurrence rate in the subtotal resection group was significantly higher than that in the total resection group (χ ²=9.484, P<0.05). The 1-, 2-, 3-, 4- and 5-year progression-free survival rates were 92.5%, 86.0%, 80.6%, 77.5% and 66.8%, respectively. The 2-, 3-, 4- and 5-year overall survival rates were 97.2%, 90.8%, 87.7% and 84.5%, respectively. Multivariate analysis showed that patients with subtotal resection(HR=3.608, P<0.05) and bi-hemisphere(HR=3.183, P<0.05)were significantly correlated with the progression free survival. Conclusions Postoperative intensity modulated radiotherapy for grade Ⅱ gliomas can achieve a better PFS. Recurrence in the radiation field is the main failure mode. Initial resection status and bi-hemisphere of tumor are important influential factors for PFS of grade Ⅱ gliomas patients.

Objective:To investigate the impact of severe stenosis or occlusion of intracranial artery in anterior and posterior circulation on cognitive function in patients.Methods:Patients with Alberta stroke program early CT score(ASPECTS) and posterior circulation ASPECTS(pc-ASPECTS) of 10 were selected, and neuropsychological assessments were performed in 30 patients with intracranial artery severe stenosis or occlusion in anterior posterior circulation (anterior circulation group)and 23 patients with intracranial artery severe stenosis or occlusion in posterior circulation(posterior circulation group) and 53 control subjects using MMSE, MoCA and multidimensional psychological assessment system.Results:The scores of time orientation(control group: 5.00(5.00, 10.00), anterior circulation group: 5.00(5.00, 5.00), posterior circulation group: 5.00(5.00, 5.00)), attention (control group: 6.00(5.00, 6.00), anterior circulation group: 5.00(4.00, 6.00), posterior circulation group: 5.00(4.00, 6.00)) and word discrimination test (control group: 70.00(60.00, 82.00), anterior circulation group: 48.00(20.50, 67.50), posterior circulation group: 53.50(33.25, 75.25)) were significantly lower in patients of anterior circulation group and posterior circulation group than those of control group(all P<0.05); The scores of memory(control group: 3.00(2.00, 3.00), anterior circulation group: 2.00(1.00, 3.00), MMSE(control group: 29.00(28.00, 30.00), anterior circulation group: 28.00(26.75, 29.00)) and simple subtraction(control group: 72.00(53.50, 85.50), anterior circulation group: 53.50(37.00, 73.00)) were significantly lower in patients of anterior circulation group than those of control group(all P<0.05); The scores of visuospatial executive function(control group: 4.00(3.00, 5.00), posterior circulation group: 3.00(2.00, 4.00)) and digital sequence reasoning(control group: 74.50(51.50, 83.00), posterior circulation group: 42.00(28.00, 70.00)) were significantly lower in patients of posterior circulation group than those of control group(all P<0.05); The scores of spatial working memory test(control group: 77.50(51.75, 89.00), anterior circulation group: 56.50(34.00, 72.50), posterior circulation group: 31.00(18.50, 58.00))were significantly lower in patients of posterior circulation group than those of the other two groups(all P<0.05). Conclusion:Severe stenosis or occlusion of intracranial arteries in anterior and posterior circulation is associated with cognitive impairment in patients.Vascular lesions in different parts can lead to cognitive impairment in different aspects.

Objective:To evaluate the safety and efficacy of endovascular interventional treatment of the intracranial vertebrobasilar trunk large aneurysms (VBTLAs) compared with conservative treatment.Methods:This is a prospective multi-center cohort study. From October 2012 to October 2018, a total of 69 patients with intracranial vertebrobasilar trunk large aneurysm (diameter>10 mm) from Henan Province People's Hospital and People's Liberation Army Rocket Medical Center were included in this study. Patients themselves chose either endovascular interventional therapy (interventional group) or conservative treatment (conservative group) after discussion with their doctors. The χ 2 test was used to compare the incidence of deaths, stroke, and all other serious adverse events including other site bleeding, myocardial infarction and others between the two groups. Results:A total of 69 patients were enrolled, of whom 51 patients were enrolled in interventional group, 18 patients underwent endovascular reconstructive therapy, 11 patients underwent deconstructive therapy, and 4 patients underwent conjunction interventional treatments. Eighteen patients were enrolled in conservative group, of whom 11 cases received simple risk factor control, 7 cases received antiplatelet and risk factors control. The proportions of hypertensive patients 94.4% (17/18) and giant aneurysms 50.0% (9/18) in the conservative group were higher than those in the surgery group 64.7% (33/51, χ 2=4.500, P=0.034), 19.6% (10/51, χ 2=4.730, P= 0.030).The incidence of all serious adverse events associated with protocol was 15.7% (8/51) in the interventional group and 44.4% (8/18) in the conservative group [risk ratio (RR) =0.353, 95% confidence intervals (CI): 0.156-0.801], and the difference was significant (χ 2=4.668, P=0.031). The incidence of fatal events associated with protocol was 2.0% (1/51) in the interventional group and 38.9% (7/18) in the conservative group (RR=0.050, 95%CI: 0.007-0.382), and the difference was significant (χ 2=14.281, P<0.001). The incidence of hemorrhage events associated with protocol was 2.0% (1/51) in the interventional group and 22.2% (4/18) in the conservative group (RR=0.088, 95%CI: 0.011-0.738), and the difference was significant (χ 2 =5.391, P=0.020). Follow-up imaging showed that the occlusion rate of aneurysms in 44 patients in the interventional group was 56.8% (25/44) after a median follow-up of 6 months. Imaging follow-up was obtained in 9 patients, whose occlusion rate of aneurysms was 0 and the median follow-up time was 12 months, in the conservative group. The difference was significant(χ 2 =7.534, P=0.006). Conclusion:Compared with conservative treatment, endovascular intervention of the intracranial VBTLAs has lower incidences of serious adverse events and death events.

Objective:To explore the diagnosis and treatment of focal segmental glomerulosclerosis (FSGS) post-kidney transplantation in children.Methods:Clinical data were retrospectively analyzed for 6 FSGS children after transplantation from 2015 to 2019. Massive proteinuria (3.2-13 g/24 h) occurred at 4 days-49 days post-transplantation. For proteinuria, glucocorticoid plus therapeutic plasma exchange and/or rituximab were provided with supplemental ACEI/ARB drugs. Five cases received tacrolimus as maintenance therapy while another case had cyclosporin A as an initial intensive therapy and switched to tacrolimus.Results:Four cases achieved complete remission after therapy. One recipient showed partial remission. During a follow up period of 11 months to 4 years, serum creatinine remained normal and stable in five cases while one died from severe pulmonary infection.Conclusions:Once FSGS occurs post-transplantation, prompt treatment of pulse glucocorticoid plus therapeutic plasma exchange and/or rituximab with supplemental ACEI/ARB drugs may yield favorable outcomes.

Objective To analyze the effect of ultrasound-guided glucocorticoid injection on different pathologies of the shoulder retrospectively.Methods Clinical data were collected describing 75 patients with shoulder pain who received ultrasound-guided glucocorticoid injection and finished 3 month follow-ups in the rehabilitation clinic of the Third Affiliated Hospital of Sun Yat-sen University between April and September of 2017.The patients were divided into three groups based on their different injection sites:group 1 was injected at the subacromial bursa alone,group 2 was injected at both the subacromial bursa and the coracoid bursa,while group 3 was injected at the subacromial bursa and the long head of the tendon sheath of the biceps brachii.A shoulder pain and disability index (SPADI) was used to quantify the pain and disability of each patient before and after the injection.Results Significant improvement was observed in the average pain and disability scores of all groups at 1 week,1 month and 3 months after the injection.Moreover,significant and continuous improvement was observed in the average pain and disability scores of groups 1 and 3,as well as the average disability score of group 2 from right after the injection until the last follow-up.However,no significant differences were found in the average pain score between one and three months after the injection.There was no significant difference among the 3 groups in the average pain and disability scores before and immediately after the injection.Conclusion Ultrasound-guided glucocorticoid injection is effective and persistent for treating shoulder pain with different pathologies.