Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

Objective To explore the clinical significance of long non-coding RNA(lncRNA)VIM-AS5 expres-sion in human breast cancer tissues and its regulatory mechanism involved in cancer cell proliferation and mi-gration.Methods The Lnc2Cancer 3.0 database was used to analyze the expression of VIM-AS5 in breast cancer tissues and its correlation with the clinical stage and survival time of breast cancer patients.RT-qPCR was used to detect the expression of VIM-AS5 in breast cancer cell lines BT-549,MDA-MB-435,MDA-MB-231 and CAL-51.Plasmid with VIM-AS5 overexpression and negative control were all transfected into CAL-51 cells through liposome recorded as VIM-AS5 group and NC group,respectively.The proliferation and migration of CAL-51 cells were detected by colony formation assay and scratch healing method,respectively.Dual-lucif-erase reporter gene experiment verified the targeting relationship between VIM-AS5 and miR-500a.RT-qPCR was used to detect the expression of miR-500a in CAL-51 cells.Western blot was used to detect the expression of JAK/STAT3 pathway in CAL-51 cells.Results The expression of VIM-AS5 in breast cancer tissues was significantly lower than that in adjacent tissues(P＜0.01).VIM-AS5 expression was negatively correlated with the clinical stage of breast cancer patients(P＜0.01).The survival time of breast cancer patients with low VIM-AS5 expression was significantly shorter than that of breast cancer patients with high VIM-AS5 ex-pression(P＜0.01).Compared with mammary epithelial cell line MCF-10 A cells,VIM-AS5 expression was significantly reduced in breast cancer cells(P＜0.01).The counting number of colony formed in the VIM-AS5 group was significantly lower than that in the NC group(P＜0.01).The cell migration rate in the VIM-AS5 group was significantly lower than that in the NC group(P＜0.01).Dual-luciferase reporter gene experiment confirmed that miR-500a was the target gene of VIM-AS5(P＜0.01).VIM-AS5 can negatively regulate the expression of miR-500a(P＜0.01).Compared with the NC group,the expression of JAK/STAT3 pathway proteins JAK,p-STAT3,c-Myc,Bcl-2,and CDK3 in CAL-51 cells of the VIM-AS5 group were significantly decreased.Conclusions VIM-AS5 is low-expressed in breast cancer cells,and up-regulation of VIM-AS5 may inhibit the proliferation and migration of breast cancer cells CAL-51 by targeting at miR-500a/JAK/STAT3 pathway.

Objective To understand the characteristics and temporal trends of stroke incidence in the household population of Shanghai's Qingpu District and to provide a basis for the development of comprehensive prevention and control strategies. Methods The stroke case database for Qingpu District from 2017-2022 was obtained from the Shanghai Stroke and Acute Myocardial Infarction Registry and Reporting Information System. The average age of onset, incidence rate, standardised incidence rate, and constitutive ratio were calculated. Independent samples t-tests were used for comparisons between groups, 2-tests and 2-trend tests for comparisons of rates, and the Joinpoint regression model for calculating the annual percentage change (APC) to analyse the temporal trend of rates. Results Between 2017 and 2022, the average age of stroke onset in the household population of Shanghai's Qingpu District was 73.69±11.60 years. The average annual incidence rate was 556.62/100 000, with an average annual standardised incidence rate of 333.76/100000. There was an increasing trend in the incidence and standardised incidence of stroke in males (APC=7.06%, t=3.44, P=0.03, APC=5.32%, t=3.04, P=0.04). The incidence of stroke increases with age, with cases mainly concentrated in those aged 65 years and above, accounting for 79.47%. Ischemic stroke dominates the stroke typology, accounting for 91.08% of cases, while the incidence of hemorrhagic stroke shows an increasing trend (APC=4.64%, t=4.59, P=0.01). Conclusion The occurrence of stroke in the general population of Shanghai’s Qingpu District is concerning. The study indicates that males, individuals aged 65 years and above, and ischaemic stroke are significant factors that require attention for stroke prevention and control.

Objective To optimize the preparation process of hydroxysafflor yellow A(HSYA)nanoparticle and conduct in vitro release evaluation.Methods HSYA nanoparticles were prepared with PLGA as carrier by modified compound emulsion method.The optimal preparation process of the experiment was selected by Plackett-Burman and Box-Behnken response surface method.The nanoparticles were characterized by using particle size analyzer,TEM scanning electron microscope,Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD).Frozen(4℃)storage stability,stability in physiological medium,lyophilized protective agent and in vitro release rate were investigated.Results The optimal process prescription of nanoparticle is as follow:pH value is 6.95,the dosage is 2.8 mg,and carrier dosage is 18.2 mg.The size of nanoparticles obtained at optimum condition is(176.4±1.29)nm,the polydiseperse index(PDI)is 0.152±0.014,the Zeta potential is(-17.6±0.46)mV,the encapsulation rate is(78.5±0.49)％,drug loading is(7.3±0.07)％.These nanoparticles showed round and good dispersion.Good stability in 4℃ storage environment and different physiological media of nanoparticles were observed.The best lyophilized protective agent was 1％glucose and the in vitro release rate of nanoparticles at 48 hours was 85％.Conclusion The optimization method is reasonable and reliable.The obtained nanoparticles have good stability and sustained-release effect.The in vitro release behavior conformed to first-order kinetic model.

Objective To investigate the feasibility of AccuLearning system for the auto-segmentation of target areas and organs-at-risk(OAR)for total marrow and lymphoid irradiation(TMLI)in children.Methods Thirty pediatric patients who underwent TMLI since 2018 to 2022 were selected.The patients were immobilized in the supine position,and their CT images were acquired on the Philips Brilliance Big Bore CT scanner.After the target areas and OAR were manually delineated and modified,the CT images and manually delineated contours were imported into AccuLearning system for training,validation,and testing of the auto-segmentation model.The auto-segmentation results in 6 TMLI patients in the test set were evaluated in terms of Dice similarity coefficient(DSC),95%Hausdorff distance and average surface distance.Results On the test set with 6 cases,except for the lens that was difficult to be delineated automatically,the DSC values was above 0.70 for all other target areas and OAR,with only one patient having a DSC value of 0.59 for the stomach.The average DSC value for the stomach in all 6 patients was 0.76,and the average DSC values for the other organs were above 0.80.Conclusion The target areas and OAR automatically delineated with the model can meet the requirements of clinical planning after simple modifications.

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·Transcriptomic and lipidomic analysis techniques were used to investigate the role of transient receptor potential vanilloid type 1(TRPV1)channel activation in the regulation of high-fat diet-induced microglial metabolism.Methods· Eight-week-old C57BL/6J mice(WT)and Trpvl-/-(KO)mice were used as experimental animals,and fed high-fat diet(HFD)for 3 days,7 days,and 8 weeks to induce modelling(WT and KO groups,n=3;WT-HFD and KO-HFD groups,n=4).TRPV1 channel expression and cellular localisation were measured by immunofluorescence in the brains of mice in the WT-HFD and KO-HFD group.RNA sequencing and liquid chromatography-mass spectrometry were performed to determine the brain phenotype of mice in the WT-HFD and KO-HFD groups.Results·The expression level of Trpvl mRNA in microglia was significantly increased in mice in the WT-HFD group compared to mice in the WT group.The expression levels of genes related to brain lipid metabolism,mitochondrial function,glucose transfer,and glycolysis were down-regulated in the KO-HFD group of mice compared with the WT-HFD group of mice.Lipidomic analysis showed that although lipids accumulated in the brain tissue of mice in the KO-HFD group,Trpv1 knockdown attenuated HFD-induced microglia activation,and in addition the TRPV1 agonist capsaicin attenuated palmitate-induced depolarisation of mitochondrial membrane potential in vitro.Conclusion·Together,these findings suggest that TRPV1 regulates lipid and glucose metabolism in microglia via fuel availability driven by a mitochondrial mechanism.

Purpose: We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. Materials and Methods: This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. Results: The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. Conclusion EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Objective:To investigate the correlation between triglyceride glucose (TyG) index and severe hypertriglyceridemic pancreatitis (HTGP), and to provide assistance for early evaluation and clinical decision-making of HTGP.Methods:From January 2016 to December 2021, the clinical data of 770 patients diagnosed with HTGP at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were retrospectively collected. According to severity of pancreatitis, the patients were divided into mild acute pancreatitis (MAP), moderate severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) groups, and the differences in TyG index among the 3 groups was compared. According to the quartile range of the TyG index, the patients were divided into TyG Q1, Q2, Q3 and Q4 groups, and the distribution of severity of pancreatitis in each TyG index quartile group was calculated. Kruskal-Wallis H test was used for statistical analysis. Spearman correlation analysis was used to analyze the correlation between TyG index quartile range and the severity of pancreatitis. Linear trend chi-square test was used to analyze the trend of SAP incidence among groups. Binary logistic regression was used to analyze the relationship between TyG index quartile range and the risk of SAP, and the trend test was also conducted. Results:A total of 770 patients with HTGP were included, among them 330 (42.9%), 268 (34.8%) and 172 (22.3%) were MAP, MSAP and SAP, respectively. The TyG indices of MAP, MSAP and SAP group were 11.8(11.3, 12.4), 12.5(11.9, 13.2) and 12.7(12.1, 13.4), respectively, and the differences among the 3 groups were statistically significant ( H=121.77, P<0.001). The TyG index was 12.21 (11.57, 12.94) in the 770 patients. There were 192, 193, 193 and 192 patients enrolled in TyG Q1(TyG index <11.57)、 Q2(TyG index ranged from 11.57 to <12.21)、 Q3(TyG index ranged from 12.21 to <12.94) and Q4(TyG index≥12.94) group, respectively.The correlation test showed that the difference between TyG quartile range and the severity of pancreatitis was statistically significant ( ρ=0.372, P<0.001). The incidence of SAP in TyG Q1, Q2, Q3 and Q4 group was 10.9%(21/192), 14.5%(28/193), 27.5%(53/193) and 36.5%(70/192), respectively. The trend test of SAP incidence among the TyG gruops was statistically significant ( χ2 =44.33, P<0.001). After adjusting for confounding factors, taking the TyG Q1 group as a reference, the OR values of SAP risk (95% confidence interval) of the TyG Q2, Q3 and Q4 groups were 1.250 (0.619 to 2.524), 2.882 (1.506 to 5.514) and 6.660 (3.456 to 12.836), respectively, and the trend test of SAP risk showed a significant difference ( OR=2.508, 95%confidence interval 1.883 to 3.341, P<0.001). Conclusions:There is a correlation between TyG index and severity of pancreatitis in patients with HTGP. As the TyG index increases, the risk of SAP increases in HTGP patients. TyG index may be an early predictor of severe HTGP.

Objective:Efficacy and safety of robot-assisted laparoscopic adrenalectomy as a treatment for large adrenal tumors.Three-dimensional(3D) reconstruction can effectively assist in preoperative planning of robotic adrenalectomy and reduce potential complications.Methods:We retrospectively reviewed the relevant information of patients who had a preoperative 3D reconstruction and underwent RA for adrenal masses larger than 10 cm. Thirteen male patients and sixteen female patients were included. The median(range) age was 43(25, 57) years old and the median tumor diameter was 12.1(10.3, 16.2) cm. The patients underwent preoperative CT enhancement scanning, and three-dimensional images were reconstructed based on the examination data. Robot-assisted laparoscopic adrenalectomy was performed under general anesthesia in 29 cases in this cohort.Results:All surgeries were completed successfully without major complications such as massive bleeding, secondary surgery, or even patient death. The median operative time was 131 (80, 245) min, and the median intraoperative bleeding was 330 (50, 2 200 ml) ml. 9 patients received blood transfusions. There were 11 cases of pheochromocytoma (37.9%), 10 cases of adenocarcinoma (34.5%) as well as 2 cases of teratoma (6.9%) and 6 cases of cortical carcinoma (20.7%). The patients were followed up for a median of 30 months after surgery. Except for 3 cases lost to follow-up and 2 patients with cortical cancer who developed recurrence or metastasis after surgery and died at 16 and 23 months after surgery, respectively, the remaining 24 cases have survived to date.Conclusions:RA is a safe and effective treatment for huge adrenal tumors. The 3D reconstruction could help the preoperative planning of RA and reduce potential complications.