OBJECTIVE To investigate the potential mechanism of the effect of ginkgo flavone aglycone （GA） against doxorubicin （DOX）-induced cardiotoxicity. METHODS The male ICR mice were randomized into control group （CON group）， model group （DOX group） and GA+DOX group （GDOX group）， with 12 mice in each group. The DOX group was injected with DOX solution at a dose of 3 mg/kg via tail vein every other day， and the GDOX group was given GA suspension intragastrically at a dose of 100 mg/kg every day+DOX solution at a dose of 3 mg/kg via tail vein every other day， for 15 consecutive days. After the end of administration， the serum levels of aspartate aminotransferase（AST）， creatine kinase（CK）， creatine kinase isoenzyme（CK- MB） and lactate dehydrogenase（LDH） in mice were detected in each group. Based on the metabolomics method， UHPLC-Q- Exactive Orbitrap HRMS method was used； based on principal component analysis （PCA） and orthogonal partial least squares- discriminant analysis （OPLS-DA）， the differentially expressed metabolites （DEMs） were screened using the criteria of variable importance in the projection≥1， fold change of peak area＞1 and P＜0.05； biological analysis was conducted based on databases such as HMDB and PubChem. RESULTS Compared with CON group， serum levels of AST， CK， CK-MB and LDH were increased significantly in DOX group （P＜0.05）； compared with DOX group， the serum levels of the above indicators （except for CK-MB） were decreased significantly in GDOX group （P＜0.05）. PCA and OPLS-DA showed that myocardial tissue samples of CON group， DOX group and GDOX group were isolated completely. After database matching， 37 common DEMs were identified， among which 17 DEMs were significantly up-regulated in the DOX group and significantly down- regulated in the GDOX group， and 8 DEMs were significantly down-regulated in the DOX group and significantly up-regulated in the GDOX group； pathway enrichment involved the biosynthesis of unsaturated fatty acids， arachidonic acid metabolism， linoleic acid metabolism， taurine and hypotaurine metabolism； the key metabolites in the above pathways included docosahexaenoic acid， arachidonic acid， phosphatidylcholine （16∶0/18∶3） and taurine. CONCLUSIONS GA may regulate the biosynthesis of unsaturated fatty acids， arachidonic acid metabolism and other metabolic pathways by acting on the core metabolites such as docosahexaenoic acid and arachidonic acid， thus alleviating the cardiotoxic effects of DOX.

OBJECTIVE To investigate the mechanism by which Ginkgo flavone aglycone （GA） reduces the cardiotoxicity of doxorubicin （DOX） based on transcriptomics and proteomics. METHODS Thirty-six mice were randomly assigned to control group （CON group， tail vein injection of equal volume of physiological saline every other day+daily intragastric administration of an equal volume of physiological saline）， DOX group （tail vein injection of 3 mg/kg DOX every other day）， and GDOX group （daily intragastric administration of 100 mg/kg GA+tail vein injection of 3 mg/kg DOX every other day）， with 12 mice in each group. The administration of drugs/physiological saline was continued for 15 days. Mouse heart tissues were collected for RNA-Seq transcriptomic sequencing and 4D-Label-free quantitative proteomic analysis to screen differentially expressed genes and proteins， which were then subjected to Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. The expression levels of Apelin peptide （Apelin）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） mRNA and protein in mouse heart tissues， as well as the phosphorylation levels of PI3K and Akt proteins， were verified. H9c2 cardiomyocytes were divided into control group （CON group）， DOX group （2 μmol/L）， and GDOX group （2 μg/mL GA+2 μmol/L DOX） to determine cell viability and the levels of key glycolytic substances in the cells. RESULTS Six common pathways were identified from transcriptomics and proteomics， including the Apelin signaling pathway， the PI3K-Akt signaling pathway， and insulin resistance. Among them， the Apelin and PI3K-Akt signaling pathways were the most enriched in terms of gene numbers. Target validation experiments showed that compared to the CON group， the relative expression of Apelin， PI3K and Akt mRNA and protein levels， as well as the phosphorylation levels of PI3K and Akt proteins， were significantly decreased in the DOX group （P＜0.05 or P＜0.01）. The relative expression of Apelin， PI3K and Akt mRNA and the phosphorylation levels of PI3K and Akt proteins were significantly increased in the GDOX group as compared with the DOX group （P＜0.05 or P＜0.01）. Cellular experiments indicated that compared to the CON group， cell viability in the DOX group was significantly decreased （P＜0.05）， the relative uptake of glucose and the relative production of pyruvate and lactate were significantly increased （P＜0.05）， and the relative production of ATP was significantly reduced （P＜0.05）. Compared to the DOX group， cell viability in the GDOX group was significantly increased （P＜ 0.05）， and the relative production of pyruvate and lactate was significantly reduced （P＜0.05）. CONCLUSIONS GA may alleviate DOX-induced cardiotoxicity by upregulating the mRNA and protein expression of Apelin， PI3K， and Akt in heart tissues， and regulating glycolytic processes.

BACKGROUND:Irisin,a myokine isolated from the transmembrane protein FNDC5 by muscle cells during exercise,has the function of inducing the browning of white adipose tissue,but its effect on lipotoxicity-induced osteogenic differentiation and the mechanism is unclear. OBJECTIVE:To investigate the effect of irisin on the osteogenic ability of palmitic acid-induced bone marrow mesenchymal stem cells and the mechanism of action. METHODS:CCK-8 assay was used to detect the effect of different concentrations of palmitic acid on the proliferation of mouse bone marrow mesenchymal stem cells and the effect of irisin on the proliferation of mouse bone marrow mesenchymal stem cells in the presence of palmitic acid.After pretreatment with irisin and palmitic acid for 24 hours,osteogenic differentiation of mouse bone marrow mesenchymal stem cells was induced by alkaline phosphatase staining as well as qRT-PCR was performed to detect the expression of osteogenesis-related genes on day 7 of osteogenic induction culture.The expression of proteins related to the AMPK/BMP2/SMAD signaling pathway was detected by western blot assay.Alizarin red staining was conducted on day 21 to detect osteogenic differences. RESULTS AND CONCLUSION:(1)The CCK-8 assay results suggested that the amplification of bone marrow mesenchymal stem cells was inversely proportional to the concentration of palmitic acid,but at 0.02 mmol/L concentration,palmitic acid had no significant effect on the amplification of bone marrow mesenchymal stem cells,and irisin did not affect the proliferation of bone marrow mesenchymal stem cells when its mass concentration was in the range of 0.1-20 μg/L.(2)Alkaline phosphatase staining and alizarin red staining showed that palmitic acid inhibited the osteogenic differentiation ability of bone marrow mesenchymal stem cells.Irisin improved palmitic acid-induced osteogenic inhibition of bone marrow mesenchymal stem cells.qRT-PCR results showed that palmitic acid could cause the downregulation of osteogenic-related genes,and irisin could inhibit this trend.(3)Western blot assay results showed that compared with the palmitic acid intervention group,irisin treatment enhanced AMPK/BMP2/SMAD signal transduction in bone marrow mesenchymal stem cells.It is found that irisin can improve the osteogenic differentiation ability of bone marrow mesenchymal stem cells pretreated with palmitic acid,and proposed that the specific mechanism might be mediated by AMPK/BMP/SMAD signaling pathway.

OBJECTIVE To establish the quality control method for the roots and rhizoma of Toricellia angulata. METHODS The properties of the roots and rhizoma of T. angulata were observed and microscopic identification was conducted. The moisture， total ash， acid-insoluble ash and ethanol-soluble extract were examined according to the method stated in the 2020 edition of Chinese Pharmacopoeia （part Ⅳ）. HPLC fingerprints of 11 batches of the roots and rhizoma of T. angulata were established， common peaks were identified and the similarity was evaluated by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition）. The contents of coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D-glucopyranoside and syringaresinol were determined by HPLC. RESULTS The properties and microscopic identification of the roots and rhizoma of T. angulata were obvious. The average contents of moisture， total ash， acid-insoluble ash and ethanol-soluble extract were 7.54%， 2.18%， 0.15% and 7.81%， respectively. There were 16 common peaks marked in the HPLC fingerprints of 11 batches of the roots and rhizoma of T. angulata， with similarities of 0.856-0.960； five of them were identified， such as coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D-glucopyranoside and syringaresinol. The contents of the above five components were 0.047 2-0.401 6， 0.836 8-8.697 9， 1.245 3-10.950 0， 0.139 0-0.437 8 and 0.016 4-0.635 3 mg/g， respectively. CONCLUSIONS The established method is stable and accurate， which can be used for the quality control of the roots and rhizoma of T. angulata. It is preliminarily proposed that the moisture in the roots and rhizoma of T. angulata is not more than 11.0%， the total ash is not more than 4.0%， the ethanol-soluble extract is not less than 5.0%， the contents of coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D- glucopyranoside and syringaresinol are not less than 0.04，0.83， 1.24， 0.13， 0.01 mg/g， respectively.

Background Alzheimer's disease(AD)is the most common type of dementia.There has been an increasing trend in incidence rate.The drug therapy has been proven ineffective in improving the cognitive function of AD patients or delaying the disease progression,leading to perceived low adherence with treatment and low efficacy.Previous basic research shows that blue light irradiation is helpful to improve the cognitive function of AD model rats,but there is no corresponding clinical study on the improvement effect of blue light irradiation on cognitive function of AD patients.Objective To explore the efficacy of blue light irradiation in improving the cognitive function of AD patients,so as to provide references for cognitive stabilization or improvement of AD patients.Methods A sample of 155 patients who were hospitalized in Geriatric Department of Shenzhen Kangning Hospital from June 2019 to December 2023 and met the International Classification of Diseases,tenth edition(ICD-10)diagnostic criteria for AD were retrospectively selected.Among them,80 cases who received blue light irradiation combined with memantine therapy and conventional psychotherapy were the study group,and 75 cases who only received memantine therapy and conventional psychotherapy were the control group.Blue light irradiation therapy lasted for 4 weeks,5 times per week,with each session lasting for 30 min.Then Mini-Mental State Examination(MMSE)and Activity of Daily Living Scale(ADL)were administered at the baseline and after treatment.Results After treatment,study group reported an increase in MMSE total score,orientation,immediate recall,attention/calculation,delayed recall and language dimension scores(Z=-6.931,-5.773,-4.123,-3.649,-3.508,-4.733,P<0.05),and a decrease in ADL total score(Z=-7.020,P<0.05)compared to baseline data.Analysis indicated that study group scored higher on MMSE total scale,orientation,immediate recall and language dimensions(Z=-2.784,-4.621,-2.483,-3.463,P<0.05),and lower on ADL total score(Z=-3.704,P<0.05)than those of control group after treatment.Conclusion Blue light irradiation for AD patients may improve their cognitive function and activities of daily living.

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.

Objective:To compare the palmar minimally invasive approach by a single incision versus palmar traditional approach for implantation of a locking plate in the treatment of distal radius fractures.Methods:A retrospective analysis was conducted of the 116 patients with distal radius fracture who had been treated with locking plates implanted through a palmar approach at Department of Traumatic Orthopedics, Wuxi Ninth People's Hospital from January 2019 to December 2022. There were 51 males and 65 females aged (57.0±10.6) years. According to the difference in palmar approach, they were divided into a traditional group of 65 cases treated with a traditional palmar approach and a minimally invasive group of 51 cases treated with a minimally invasive palmar approach through a single 1.5 cm incision. The surgical time, intraoperative bleeding, incision length, incision healing, fracture healing time, pain visual analogue scale (VAS) on the 1st and 7th days after surgery, range of motion and grip strength of the affected wrist, and imaging results at the last follow-up were recorded and compared between the 2 groups. The patient rated wrist evaluation (PRWE) and Gartland-Werley wrist evaluation were used to assess functional recovery of the wrist affected at the last follow-up.Results:There was no statistically significant difference in the baseline data between the 2 groups, indicating comparability ( P>0.05). All patients were followed-up for (13.6±2.1) months. All fractures healed. The intraoperative bleeding [(27.3±3.6) mL] in the minimally invasive group was significantly less than that in the traditional group [(41.2±6.8) mL], the incision length [(1.6±0.1) cm] in the former was significantly shorter than that in latter [(6.6 ± 0.6) cm], the postoperative VAS for pain on the 7th day after surgery [(1.8±0.8) points] and incidence of complications [2.0% (1/51)] in the former were significantly lower than those in the latter [(3.0±0.6) points, 12.3% (8/65)] ( P<0.05). However, the surgical time [(70.4±6.9) min] in the former was significantly longer than that in the latter [(67.2±8.0) min] ( P<0.05). There was no statistically significant difference between the 2 groups in terms of incision healing, fracture healing time, VAS for pain on the first postoperative day, wrist range of movement at the last follow-up, grip strength, PRWE score, Gartland-Werley functional recovery, fracture alignment, palm angle, ulnar deviation angle, and radial height at the last follow-up ( P>0.05). Conclusions:Both the palmar minimally invasive approach by a single incision and the traditional palmar approach are effective for implantation of a locking plate in the treatment of distal radius fractures. However, the minimally invasive palmar approach is superior to the traditional palmar approach in terms of incision aesthetics, intraoperative bleeding, surgical trauma response, surgical time and surgical risk.

Humans ; Transcranial Magnetic Stimulation ; Pain Management ; Psychotic Disorders/therapy* ; Depressive Disorder, Major ; Treatment Outcome ; Transcranial Direct Current Stimulation

BackgroundThe diagnosis of Alzheimer's disease （AD） still faces great challenges， and the advantage of electroencephalogram （EEG） diagnosis lies in its portable and non-invasive nature， so the EEG diagnosis of AD has occupied an important place in clinical research. ObjectiveTo evaluate the value of resting state EEG for AD diagnosis， and to provide references for early recognition of AD in clinical practice. MethodsClinical data of AD patients （n=59） in an Inpatient Geriatric Psychiatry Unit of Shenzhen Kangning Hospital from May 2019 to May 2022 were retrospectively analyzed， and healthy elderly individuals attending outpatient clinics at the hospital during the same period were enrolled as control group （n=54）. Eight-channel resting state EEG data were acquired， and the absolute power values in the α， β， θ and δ frequency bands and the α/θ ratio were obtained and calculated using Fast Fourier Transform （FFT）. Cognitive function assessments of patients were done by Mini-Mental State Examination （MMSE） and Montreal Cognitive Assessment （MoCA）. Spearman correlation analysis was used to examine the correlation between EEG findings and MMSE and MoCA scores of AD patienrs. Logistic regression prediction model for AD was built using currently available EEG and clinical variables， and the model performance was assessed using the receiver operating characteristic （ROC） curve and the area under curve （AUC）. ResultsThe θ-band absolute powers in the right mid-frontal （F4） and mid-lateral （F7， F8） regions were higher in AD patients than those in healthy controls， with statistically significant difference （t=-2.844， -2.825， -3.014， P<0.05 or 0.01）. The absolute powers of α/θ ratio in prefrontal （Fp1， Fp2）， mid-frontal （F3， F4） and mid-lateral （F7， F8） regions showed a notable reduction in AD patients compared with healthy controls， with statistical difference （t=2.081， 2.327， 3.423， 2.358， 3.272， 2.445， P<0.05 or 0.01）. Spearman correlation analysis denoted that MMSE score was positively correlated with the absolute powers of α-band， β-band and α/θ ratio （r=0.206， 0.288， 0.372， P<0.05 or 0.01）. MoCA score was positively correlated with β absolute powers and α/θ ratio （r=0.201， 0.315， P<0.05 or 0.01）， and negatively correlated with θ absolute power （r=-0.218， P<0.05）. ROC curve revealed an AUC of 0.882 （95% CI： 0.820~0.943）， a sensitivity of 0.966 and a specificity of 0.673 for the AD prediction model based on EEG variables， while the prediction model for AD using comprehensive variables achieved better predictive efficacy， reaching an AUC， sensitivity and specificity of 0.946 （95% CI： 0.905~0.986）， 0.948 and 0.873， respectively. ConclusionResting state EEG of AD patients is correlated with cognitive function， and are of great value in the diagnosis of AD， with θ absolute power and α/θ ratio in EEG being the most strongly correlated with AD.

Atrial fibrillation (AF) is one of the most common complications after cardiac surgery. The existing treatment of postoperative AF mainly focuses on preoperative prevention, intraoperative protection and postoperative treatment for factors prone to AF before, during and after surgery, but the postoperative treatment in various areas and hospitals is different. This article combines the latest literature published in Europace about the practice guidance of cardioversion of AF and atrial flutter, and summarizes the treatment of electrical cardioversion, in order to provide clinical guidance for electrical cardioversion of AF after cardiac surgery.