OBJECTIVE To study the efficacy of Tianjiang xueshuantong pills in the treatment of coronary heart disease. METHODS In accordance with the common pathogenesis of coronary heart disease， acute myocardial ischemia model， hyperlipidemia model， blood stasis model， and carotid artery thrombosis model were established using Wistar rats or SD rats as the experimental subjects. The effects of Tianjiang xueshuantong pills administered at high， medium， and low doses （0.6， 1.2 and 2.4 g/kg） on hemodynamic parameters and myocardial enzyme markers [lactate dehydrogenase （LDH）， creatine kinase-MB （CK- MB）]， oxidative stress factors [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）]， inflammatory cytokines [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， intercellular adhesion molecule-1 （ICAM-1）]， myocardial infarction percentage， serum lipid indexes [total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）]， platelet aggregation function 话：022-84845240。E-mail：jiangx@tjipr.com [maximum aggregation rate （MAR）]， and thrombus formation indexes [thrombosis time， thrombus mass， thrombus protein content， plasminogen activator inhibitor-1 （PAI-1）， and tissue-type plasminogen activator （t-PA）] were evaluated in the rat models. RESULTS In myocardial ischemia tests， Tianjiang xueshuantong pills significantly reduced the percentage of myocardial infarction and the levels of CK-MB， LDH， MDA， GSH， IL-6， TNF-α， IL- 1β， and MCP-1 in serum （P＜0.05 or P＜0.01）. In hyperlipidemia tests， high dose of Tianjiang xueshuantong pills significantly reduced the serum levels of TC， LDL and significantly increased the level of HDL in rats after 2 weeks and 4 weeks of administration. In blood stasis tests， different doses of Tianjiang xueshuantong pills significantly reduced MAR of rats （P＜0.01）. In artery thrombosis tests， high dose of Tianjiang xueshuantong pills significantly prolonged the time of thrombosis formation （P＜ 0.01）， significantly reduced the weight and protein content of thrombus and the level of PAI-1 in serum （P＜0.01）. CONCLUSIONS Tianjiang xueshuantong pills exert therapeutic effects on coronary heart disease through multi-dimensional synergistic actions， including anti-myocardial ischemia， lipid-lowering， and anti-thrombotic effects.

BACKGROUND: Post-stroke disability diminishes the physical activity (PA) level of survivors, potentially affecting their long-term prognosis. This study endeavors to explore the correlation between daily PA level and the all-cause mortality in patients with a history of stoke in the United States. METHODS: Data of stroke survivors were sourced from the National Health and Nutritional Examination Survey (NHANES) 2007-2018. The population was stratified into three groups based on their PA level. Kaplan-Meier method with log-rank tests for significance was used for survival analysis. Weighted Cox proportional hazards regression models were employed to estimate the hazard ratios (HRs) for all-cause mortality. Subgroup analysis was conducted to strengthen the results. RESULTS: A total of 1395 participants were recruited, comprising 679 males and 716 females, with a median age of 68 years. Based on their PA levels, 779 individuals were classified as inactive, 156 as insufficiently active, and 460 as sufficiently active. Following a median observation period of 59 months, there were 476 recorded deaths, with 349, 47, and 80 cases in the three respective groups. Compared to the inactive group, the HRs and 95% confidence intervals (CIs) for all-cause mortality in participants who were insufficiently active and sufficiently active were 0.58 (0.40, 0.84) and 0.47 (0.33, 0.67), respectively. The Kaplan-Meier curve revealed a significant difference in overall survival between the three groups, as confirmed by the log-rank test (P < 0.0001). Subgroup analysis further validated our results and demonstrated that the protective impact of PA on stroke prognosis varies according to distinct characteristics. CONCLUSIONS The results indicate that increased levels of PA are associated with a protective effect on long-term mortality among stroke survivors. Further prospective longitudinal studies are necessary to elucidate the optional PA level and special exercise guideline targeting this population.
Humans ; Male ; Female ; Aged ; Exercise ; Middle Aged ; Nutrition Surveys ; Stroke/mortality* ; United States/epidemiology* ; Survivors/statistics & numerical data* ; Aged, 80 and over ; Mortality

AIM: To investigate the mechanism of elemene synergistic bortezomib against multiple myeloma based on ROS-NF-κB-p38MAPK signaling pathway. METHODS: CCK-8 assay was used to detect cell activity. Nude mice were randomly divided into control group, bortezomib (BTZ) group, elemene (ELE) group and combination group. Each group was treated with BTZ, ELE and BTZ combined with ELE, respectively. Tunel staining was performed to observe the apoptosis of tumor tissues. The expressions of Caspase-3, Bcl-2, NF-κB and p38 MAPK were detected by Western Blot. Cell cycle, apoptosis and reactive oxygen species (ROS) expression were detected by flow cytometry using human myeloma U266 cells. RESULTS: When 4.0 μmol/L ELE combined with 50 nmol/L BTZ treated U266, the cell activity was significantly reduced compared with that of NC, BTZ and ELE groups (P< 0.05). The tumor volume of nude mice in BTZ group, ELE group and combined group was significantly reduced compared with the control group (P <0.05), and the combined group was the smallest. Tunel staining results showed that the apoptosis level in the control group was lower than that in the BTZ group, ELE group and the combined group (P<0.05), and the combined group had the lowest apoptosis level. Compared with the control group, the expressions of Caspase-3 and p38 MAPK in BTZ group, ELE group and combination group were significantly increased, while the expression of Bcl-2 was significantly decreased. The apoptosis level and expression of ROS in BTZ group, ELE group and the combined group was significantly increased compared with the control group (P<0.05). CONCLUSION: ELE can enhance the role of BTZ in promoting apoptosis of myeloma cells, which may be achieved by regulating ROS/NF-κB/p38 MAPK signaling pathway to enhance the level of apoptosis of tumor cells to achieve anti-tumor effect.

OBJECTIVE To explore the effects of irbesartan（Irb）combined with 5-fluorouracil（5-FU）on the proliferation and extracellular signal-regulated kinase （ERK）/peroxidase proliferator-activated receptor γ（PPARγ）signaling pathway of Lewis lung cancer cells. METHODS Lewis lung cancer cells from mice were divided into normal control （NC）group，Irb low-dose （LD）group（1×10－3 mmol/L），Irb high-dose （HD）group（1×10－1 mmol/L），5-FU group （10 μmol/L），Irb LD+ 5-FU group （Irb 1×10－3 mmol/L+5-FU 10 μmol/L）and Irb HD+ 5-FU group （Irb 1×10－1 mmol/L+5-FU 10 μmol/L）. MTT method was used to measure the activity of cell proliferation in each group. Plate colony formation experiment was used to determine the number of cell colonies formed in each group ；Western blot method was used to detect the expression levels of proliferating cell nuclear antigen （PCNA），p53，ERK1/2，p-ERK1/2 and PPAR γ protein in each group. RESULTS Compared with the NC group ，the cell proliferation activity ，the number of colonies formed and the protein levels of PCNA ，p-ERK1/2，and PPARγ were significantly reduced in the other five groups ，and the protein level of p 53 was significantly increased （P＜0.05）；the protein expression of ERK1/2 had no significant difference （P＞0.05）. The changes of above indexes in Irb LD+ 5-FU group and Irb HD+ 5-FU group were more significant than Irb LD group ，Irb HD group and 5-FU group （P＜0.05）. CONCLUSIONS Irb combined with 5-FU can inhibit the proliferation of Lewis lung cancer cell ，and the effect is better than that of the two alone. The mechanism may be related to the inhibition of ERK/PPARγ signal pathway.

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

Objective: To explore the short and mid-term efficacy of device closure of patent foramen ovale (PFO) for treating the patients with PFO combining cryptogenic stroke (CS) and transient ischemic attack (TIA). Methods: A total of 56 PFO patients with CS and TIA receiving device closure in our hospital from 2009-05 to 2015-12 were retrospectively studied. Transthoracic echocardiography (TTE), electrocardiogram (ECG), chest X-ray were examined at 24h, 1 month, 3 and 6 months after theoperation; telephone visit was conducted every 6 months thereafter. Results: There were 54/56 PFO patients combining CS and 2 combining TIA; 53 (94.6%)patients received PFO occluder from Starway medical technology. Aspirin was used for 6 months after the operation. The patients were followed-up for the average of (34.67±23.24) months. No body suffered from post-operative stroke and TIA; no residual shunt was observed. Conclusion: The short and mid-term efficacy of device closure has been satisfactory for treating the patients with PFO combining CS and TIA; its overall clinical value should be further investigated in large population and long-term study.

Objective To explore the 18F-FDG PET/CT features of sacral insufficiency fracture.Methods 18 F-FDG PET/CT imaging and clinical data of 8 patients with sacral insufficiency fracture were retrospectively analyzed.Results All 8 patients had different degrees of radioactivity uptake in sacra with the maximum standardized uptake value (SUVmax)from 2.7 to 7.2.Four patients had lesions in their left sacra,2 in the bilateral sacral wings and sacral promontories,1 in the bilateral sacral wings,and 1 in the left sacral wing and sacral promontory.There were 8 patients of longitudinal fractures in sacral wings,which of 6 patients involving S1-2 and 2 patients involving S3.Three patients had transverse fractures in sacral promontories,with 2 located at S2 and 1 at S3.The sacral bone density increased in 5 cases,and the density was not changed in 3 cases.Conclusion Sacral insufficiency fracture had specific 18F-FDG PET/CT characteristics.

Objective: To explore the imaging and clinical features of Behcet's disease with coronary artery involvement in order to improve the diagnosis and treatment in clinical practice. Methods: A total of 6 Behcet's disease patients with coronary involvement diagnosed and treated in our hospital from 1999-08 to 2016-11 were analyzed. Coronary angiography (CAG) and coronary CTA were performed for diagnosis. There were 5 cases received CAG and 5 cases received CTA examinations. Results: All 6 patients had the first clinical visit by sudden pericardial tapenade, myocardial infarction or cardiac shock. For diagnosis: the imaging presentation included coronary stenosis, occlusion and pseudo aneurysm formation. 3 patients had anterior descending artery involvement, 1 had the far-end of left circumflex involvement and 2 had the middle segment of right coronary involvement; all patients were combining large amount of pericardial effusion. For treatment: there were 3 patients with aneurysm received conservative treatment (1 case had open thoracic exploration), 1/3 lost contact and 2 having long-term normal life; 3 patients received coronary stent implantation without optimal effect. Conclusion: The patients of Behcet's disease with coronary involvement may easily form pseudo aneurysm; CAG/CTA has been helpful for diagnosis. Clear pre-operative diagnosis of etiology is important for treatment.