BACKGROUND Epilepsy impacts millions of people,with many not responding to existing treatments.Some evidence links neuroinflammatory processes to epilepsy.Statins exhibit anti-inflammatory and neuroprotective properti...BACKGROUND Epilepsy impacts millions of people,with many not responding to existing treatments.Some evidence links neuroinflammatory processes to epilepsy.Statins exhibit anti-inflammatory and neuroprotective properties,potentially offering antiepileptic effects.AIM To evaluate the anticonvulsant effects of rosuvastatin in animal models of epilepsy.METHODS Ninety-six albino mice were divided into 16 groups.In the maximal electroshock seizure(MES)model,eight groups received intraperitoneal vehicle,carbama-zepine,rosuvastatin,or a combination.Outcomes measured included seizure protection[tonic hind limb extension(THLE)],duration of THLE,seizure duration,and mortality.In the pentylenetetrazol(PTZ)model,eight groups were pretreated with vehicle,valproate,rosuvastatin,or a combination,with outcomes measured as seizure latency,seizure duration,and mortality.RESULTS In the MES model,rosuvastatin exhibited protection against THLE in a small percentage of mice.Rosuvastatin shortens the duration of THLE in a dose-dependent manner.However,none of these were statistically significant com-pared to the control group.The combination of rosuvastatin 10 mg/kg with carbamazepine 4 mg/kg resulted in a significant reduction in seizure duration compared to the control group,better than carbamazepine alone at 4 mg/kg and 6 mg/kg.In the PTZ model,rosuvastatin alone showed no significant effects on latency,duration of seizure,or mortality.However,rosuvastatin 10 mg/kg combined with valproate 100 mg/kg significantly delayed the onset of seizures,seizure duration and mortality percentage,better than valproate alone at 100 mg/kg.CONCLUSION Rosuvastatin enhanced the anticonvulsant effects of carbamazepine and valproate.Further studies are required to explore the antiepileptic potential of rosuvastatin at various doses,durations,dosage forms,routes and models.展开更多
Low-density lipoprotein cholesterol(LDL-C)is the most causal risk factor for atherosclerotic cardiovascular disease(ASCVD).Red yeast rice(RYR)is a nutraceutical widely used as a lipid-lowering dietary supplement.The m...Low-density lipoprotein cholesterol(LDL-C)is the most causal risk factor for atherosclerotic cardiovascular disease(ASCVD).Red yeast rice(RYR)is a nutraceutical widely used as a lipid-lowering dietary supplement.The main cholesterol-lower agents in RYR are monacolins,particularly monacolin K,a weak reversible inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase,whose daily consumption(up to 10 mg/day)reduces LDL-C plasma levels up to 34%within 6-8 weeks when compared to placebo.The reduction in LDL-C is often accompanied by lower levels of plasma apolipoprotein B,total cholesterol,matrix metalloproteinases 2 and 9,high-sensitivity C-reactive protein,non-high-density lipoprotein cholesterol,and blood pressure.RYR has also demonstrated favorable reductions of up to 45%compared to placebo in the risk of ASCVD events in secondary prevention studies.The mechanism of action is similar to statins.When consumed appropriately,RYR is associated with only minimal side effects.Mild myalgia may be seen in patients who cannot tolerate low-dose statins.In individuals with no additional ASCVD risk factors,RYR is a safe and effective supplement in treating mild to moderate hyperlipidemia.展开更多
Background Coronary artery calcification(CAC),a hallmark of atherosclerosis,paradoxically associates with reduced cardiovascular risk under statin therapy despite accelerated calcification progression,prompting this s...Background Coronary artery calcification(CAC),a hallmark of atherosclerosis,paradoxically associates with reduced cardiovascular risk under statin therapy despite accelerated calcification progression,prompting this study to explore CAC metrics as potential mediators between statin use and major adverse cardiovascular events(MACE).Methods Clinical data of 246 hospitalized patients who underwent coronary computed tomography angiography(CCTA)at Guangdong Provincial People's Hospital from January 2023 to June 2023 were retrospectively analyzed.Linear regression was used to evaluate the relationship between statin use and CAC parameters.Multivariable Poisson regression models were applied to explore the associations of statin use and CAC parameters with MACE risk.A mediation analysis was performed to assess the role of CAC parameters in the statin-MACE relationship.Results Statin use was independently associated with increased calcification score(β=0.648,P<0.001),CAC volume(β=0.623,P<0.001),and calcified plaque proportion(β=0.606,P=0.002).Multivariable Poisson regression indicated that statin use significantly reduced MACE risk[incidence rate ratio(IRR):0.33,P=0.018],whereas calcification score(IRR:2.63,P=0.026)and CACvolume(IRR:2.66,P=0.044)were associated with elevated MACE risk;Calcified plaque proportion showed no significant association.Mediation analysis revealed that calcification score(β=0.035,P=0.021)and CAC volume(β=0.023,P=0.018)exerted masking effects,while calcified plaque proportion had no mediating role.Conclusions Calcification score and CACvolume demonstrated limited masking effects in the association between statin use and MACE.展开更多
BACKGROUND The pleiotropic effects of statins,including anti-inflammatory and immunomodulatory actions,have prompted investigation into their perioperative role in colorectal cancer(CRC)surgery.However,findings remain...BACKGROUND The pleiotropic effects of statins,including anti-inflammatory and immunomodulatory actions,have prompted investigation into their perioperative role in colorectal cancer(CRC)surgery.However,findings remain inconsistent due to heterogeneity in study designs,statin regimens,and outcome definitions.This reviews current observational evidence,emphasizing the duration of statin therapy and its association with postoperative outcomes.AIM To evaluate the association between statin therapy and postoperative outcomes in patients undergoing CRC surgery.METHODS A systematic literature search was conducted using PubMed and Google Scholar through March 2025.Five cohort studies evaluating statin use in CRC surgery were included.Primary outcomes assessed included anastomotic leak,surgical site infection,and 30-day and 90-day mortality.Data on statin duration and confounders such as comorbidities and surgical variables were also extracted.RESULTS Three studies investigated the rates of anastomotic leaks in patients who used statins compared to those who did not.Two of the studies found no significant difference,while one noted a marginally higher leak rate among statin users.Diabetes,smoking habits,and operative time were found to be common confounding factors.Conversely,the use of statins was consistently linked to a decrease in 30-day mortality in propensity-matched groups,although findings regarding 90-day mortality were variable.CONCLUSION Statin therapy may confer short-term survival benefits in CRC surgical patients,potentially via anti-inflammatory or cytoprotective mechanisms.While evidence regarding anastomotic leaks remains inconclusive,trends suggest improved postoperative outcomes.These findings are constrained by methodological heterogeneity,underscoring the need for prospective,randomized studies to confirm benefits and identify optimal patient subgroups.展开更多
Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo(TXL)capsule to treat atherosclerosis.However,clinical evidence of the effects of TXL treatment on coronary ...Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo(TXL)capsule to treat atherosclerosis.However,clinical evidence of the effects of TXL treatment on coronary plaque vulnerability is unavailable.In response,we developed this study to investigate the hypothesis that on the basis of statin therapy,treatment with TXL capsule may stabilize coronary lesions in patients with acute coronary syndrome(ACS).The TXL-CAP study was an investigator-initiated,randomized,double-blind clinical trial conducted across 18 medical centers in China.Patients with ACS aging from 18 to 80 years old who had a non-intervened coronary target lesion with a fibrous cap thickness(FCT)<100μm and lipid arc>90°as defined by optical coherence tomography(OCT)were recruited.A total of 220 patients who met the selection criteria but did not meet the exclusion criteria will be finally recruited and randomized to receive treatment with TXL(n=110)or placebo(n=110)for a duration of 12 months.The primary endpoint was the difference in the minimum FCT of the coronary target lesion between TXL and placebo groups at the end of the 12-month follow-up.Secondary endpoints included:(1)changes of the maximum lipid arc and length of the target plaque,and the percentage of lipid,fibrous,and calcified plaques at the end of the12-month period;(2)the incidence of composite cardiovascular events and coronary revascularization within the 12 months;(3)changes in the grade and scores of the angina pectoris as assessed using the Canadian Cardiovascular Society(CCS)grading system and Seattle angina questionnaire(SAQ)score,respectively;and(4)changes in hs-CRP serum levels.The results of the TXLCAP trial will provide additional clinical data for revealing whether TXL capsules stabilizes coronary vulnerable plaques in Chinese ACS patients.展开更多
Metabolic-associated steatotic liver disease(MASLD)is a global health burden intricately linked to cardiovascular disease(CVD)through shared pathways-insulin resistance,dyslipidemia,and chronic inflammation.CVD has be...Metabolic-associated steatotic liver disease(MASLD)is a global health burden intricately linked to cardiovascular disease(CVD)through shared pathways-insulin resistance,dyslipidemia,and chronic inflammation.CVD has become the leading cause of mortality in MASLD,necessitating integrated management strategies.This review synthesizes evidence on bidirectional MASLD-CVD interactions and evaluates therapeutic approaches:Lifestyle modifications,pharmacotherapy(e.g.,GLP-1 receptor agonists,SGLT2 inhibitors,statins),and metabolic interventions.Despite progress,critical gaps persist in risk stratification tools,personalized treatment algorithms,and long-term outcomes of novel agents like resmetirom.A multidisciplinary care model,bridging hepatology and cardiology,is essential to address these challenges and improve patient outcomes.展开更多
Background: To study the influence of blood lipid levels on hemorrhagic transformation(HT) and prognosis after acute cerebral infarction(ACI).Methods: Patients with ACI within 72 h of symptoms onset between January 1 ...Background: To study the influence of blood lipid levels on hemorrhagic transformation(HT) and prognosis after acute cerebral infarction(ACI).Methods: Patients with ACI within 72 h of symptoms onset between January 1 st, 2015, and December 31 st, 2016, were retrospectively analyzed. Patients were divided into group A(without HT) and group B(HT). The outcomes were assessed after 3 months of disease onset using the modified Rankin Scale(m RS). An m RS score of 0–2 points indicated excellent prognosis, and an m RS score of 3–6 points indicated poor prognosis.Results: A total of 732 patients conformed to the inclusion criteria, including 628 in group A and 104 in group B. The incidence of HT was 14.2%, and the median onset time was 2 d(interquartile range, 1–7 d). The percentages of patients with large infarct size and cortex involvement in group B were 80.8% and 79.8%, respectively, which were both significantly higher than those in group A(28.7 and 33.4%, respectively). The incidence rate of atrial fibrillation(AF) in group B was significantly higher than that in group A(39.4% vs. 13.9%, P<0.001). The adjusted multivariate analysis results showed that large infarct size, cortex involvement and AF were independent risk factors of HT, while total cholesterol(TC) was a protective factor of HT(OR=0.359, 95% CI 0.136–0.944, P=0.038). With every 1 mmol/L reduction in normal TC levels, the risk of HT increased by 64.1%. The mortality and morbidity at 3 months in group B(21.2% and 76.7%, respectively) were both significantly higher than those in group A(8.0% and 42.8%, respectively). The adjusted multivariate analysis results showed that large infarct size(OR=12.178, 95% CI 5.390–27.516, P<0.001) was an independent risk factor of long-term unfavorable outcomes, whereas low-density lipoprotein cholesterol(LDL-C) was a protective factor(OR=0.538, 95% CI 0.300–0.964, P=0.037). With every 1 mmol/L reduction in normal LDL-C levels, the risk of an unfavorable outcome increased by 46.2%. Major therapies, including intravenous recombinant human tissue plasminogen activator(r TPA), intensive lipid-lowering statins and anti-platelets, were not significantly related to either HT or long-term, post-ACI poor prognosis.Conclusions: For patients with large infarct sizes, especially those with cortex involvement, AF, or lower levels of TC, the risk of HT might increase after ACI. The risk of a long-term unfavorable outcome in these patients might increase with a reduction in LDL-C.展开更多
3-Hydroxy-3-methylglutaryl coenzyme A （HMG CoA） reductase produces mevalonate, an important intermediate in the synthesis of cholesterol and essential nonsterol isoprenoids. The reductase is subject to an exorbitant...3-Hydroxy-3-methylglutaryl coenzyme A （HMG CoA） reductase produces mevalonate, an important intermediate in the synthesis of cholesterol and essential nonsterol isoprenoids. The reductase is subject to an exorbitant amount of feedback control through multiple mechanisms that are mediated by sterol and nonsterol end-products of mevalonate metabolism. Here, I will discuss recent advances that shed light on one mechanism for control of reductase, which involves rapid degradation of the enzyme. Accumulation of certain sterols triggers binding of reductase to endoplasmic reticulum （ER） membrane proteins called Insig-1 and Insig-2. Reductase-Insig binding results in recruitment of a membrane-associated ubiquitin ligase called gp78, which initiates ubiquitination of reductase. This ubiquitination is an obligatory reaction for recognition and degradation of reductase from ER membranes by cytosolic 26S proteasomes. Thus, sterol-accelerated degradation of reductase represents an example of how a general cellular process （ER-associated degradation） is used to control an important metabolic pathway （cholesterol synthesis）.展开更多
Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis.This article aims to provide a complete overview of pharmacothe...Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis.This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications,together with discussion of current controversies and potential future directions.PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety,efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis.Non-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices,but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation.Recent observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation.The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy;recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis.Diuretics remain the mainstay of uncomplicated ascites treatment,and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites.Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications.Despite initial hepatotoxicity concerns,safety of statin administration has been demonstrated in compensated cirrhosis.Furthermore,statins are suggested to have protective effects upon fibrosis progression,decompensation and mortality.Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting.Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis,and may impede hepatic fibrogenesis and decompensation.Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management,nutritional optimisation and patient education.展开更多
Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen specie...Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen species (ROS), altered redox state, and elevated oxidant stress have been demonstrated in the lungs and RV of several animal models of PH, including chronic hypoxia, monocrotaline toxicity, caveolin-1 knock-out mouse, and the transgenic Ren2 rat which overexpresses the mouse renin gene. Generation of ROS in these models is derived mostly from the activities of the nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase. As disease progresses circulating monocytes and bone marrow-derived monocytic progenitor cells are attracted to and accumulate in the pulmonary vasculature. Once established, these inflammatory cells generate ROS and secrete mitogenic and fibrogenic cytokines that induce cell proliferation and fibrosis in the vascular wall resulting in progressive vascular remodeling. Deficiencies in antioxidant enzymes also contribute to pulmonary hypertensive states. Current therapies were developed to improve endothelial function, reduce pulmonary artery pressure, and slow the progression of vascular remodeling in the pulmonary vasculature by targeting deficiencies in either NO (PDE-type 5 inhibition) or PGI 2 (prostacyclin analogs), or excessive synthesis of ET-1 (ET receptor blockers) with the intent to improve patient clinical status and survival. New therapies may slow disease progression to some extent, but long term management has not been achieved and mortality is still high. Although little is known concerning the effects of current pulmonary arterial hypertension treatments on RV structure and function, interest in this area is increasing. Development of therapeutic strategies that simultaneously target pathology in the pulmonary vasculature and RV may be beneficial in reducing mortality associated with RV failure.展开更多
We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuv...We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a greater potential compared with other statins to damage the liver is unclear and the involved mechanisms are also unknown. However, rosuvastatin is taken up by hepatocytes more selectively and more efficiently than other statins, and this may reasonably represent an important variable to explain the hepatotoxic potential of rosuvastatin. Our report supports the view that a clinically significant risk of liver toxicity should be considered even when rosuvastatin is given at the range of doses used in common clinical practice.展开更多
AIM:To determine the effects of curcumin,(-)-epigallocatechin-3-gallate (EGCG),lovastatin,and their combinations on inhibition of esophageal cancer.METHODS:Esophageal cancer TE-8 and SKGT-4 cell lines were subjected t...AIM:To determine the effects of curcumin,(-)-epigallocatechin-3-gallate (EGCG),lovastatin,and their combinations on inhibition of esophageal cancer.METHODS:Esophageal cancer TE-8 and SKGT-4 cell lines were subjected to cell viability methyl thiazolyl tetrazolium and tumor cell invasion assays in vitro and tumor formation and growth in nude mouse xenografts with or without curcumin,EGCG and lovastatin treatment.Gene expression was detected using immunohistochemistry and Western blotting in tumor cell lines,tumor xenografts and human esophageal cancer tissues,respectively.RESULTS:These drugs individually or in combinations significantly reduced the viability and invasion capacity of esophageal cancer cells in vitro.Molecularly,these three agents reduced the expression of phosphorylated extracellular-signal-regulated kinases (Erk1/2),c-Jun and cyclooxygenase-2 (COX-2),but activated caspase 3 in esophageal cancer cells.The nude mouse xenograft assay showed that EGCG and the combinations of curcumin,EGCG and lovastatin suppressed esophageal cancer cell growth and reduced the expression of Ki67,phosphorylated Erk1/2 and COX-2.The expression of phosphorylated Erk1/2 and COX-2 in esophageal cancer tissue specimens was also analyzed using immunohistochemistry.The data demonstrated that 77 of 156 (49.4%) tumors expressed phosphorylated Erk1/2 and that 121 of 156 (77.6%) esophageal cancers expressed COX-2 protein.In particular,phosphorylated Erk1/2 was expressed in 23 of 50 (46%) cases of esophageal squamous cell carcinoma (SCC) and in 54 of 106 (50.9%) cases of adenocarcinoma,while COX-2 was expressed in 39 of 50 (78%) esophageal SCC and in 82 of 106 (77.4%) esophageal adenocarcinoma.CONCLUSION:The combinations of curcumin,EGCG and lovastatin were able to suppress esophageal cancer cell growth in vitro and in nude mouse xenografts,these drugs also inhibited phosphorylated Erk1/2,c-Jun and COX-2 expression.展开更多
Hyperlipidemia is a well-established risk factor for developing cardiovascular disease(CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment ...Hyperlipidemia is a well-established risk factor for developing cardiovascular disease(CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors(statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein(LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsinkexin type 9(PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.展开更多
Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold stan...Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones,new perspectives regarding medical therapy of cholelithiasis are currently under discussion,also taking into account the pathogenesis of gallstones,the natural history of the disease and the analysis of the overall costs of therapy.A careful selection of patients may lead to successful nonsurgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones.The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations,suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe),or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis,might be proposed as additional approaches for treating cholesterol gallstones.In this review we discuss old,recent and future perspectives on medical treatment of cholesterol cholelithiasis.展开更多
文摘BACKGROUND Epilepsy impacts millions of people,with many not responding to existing treatments.Some evidence links neuroinflammatory processes to epilepsy.Statins exhibit anti-inflammatory and neuroprotective properties,potentially offering antiepileptic effects.AIM To evaluate the anticonvulsant effects of rosuvastatin in animal models of epilepsy.METHODS Ninety-six albino mice were divided into 16 groups.In the maximal electroshock seizure(MES)model,eight groups received intraperitoneal vehicle,carbama-zepine,rosuvastatin,or a combination.Outcomes measured included seizure protection[tonic hind limb extension(THLE)],duration of THLE,seizure duration,and mortality.In the pentylenetetrazol(PTZ)model,eight groups were pretreated with vehicle,valproate,rosuvastatin,or a combination,with outcomes measured as seizure latency,seizure duration,and mortality.RESULTS In the MES model,rosuvastatin exhibited protection against THLE in a small percentage of mice.Rosuvastatin shortens the duration of THLE in a dose-dependent manner.However,none of these were statistically significant com-pared to the control group.The combination of rosuvastatin 10 mg/kg with carbamazepine 4 mg/kg resulted in a significant reduction in seizure duration compared to the control group,better than carbamazepine alone at 4 mg/kg and 6 mg/kg.In the PTZ model,rosuvastatin alone showed no significant effects on latency,duration of seizure,or mortality.However,rosuvastatin 10 mg/kg combined with valproate 100 mg/kg significantly delayed the onset of seizures,seizure duration and mortality percentage,better than valproate alone at 100 mg/kg.CONCLUSION Rosuvastatin enhanced the anticonvulsant effects of carbamazepine and valproate.Further studies are required to explore the antiepileptic potential of rosuvastatin at various doses,durations,dosage forms,routes and models.
文摘Low-density lipoprotein cholesterol(LDL-C)is the most causal risk factor for atherosclerotic cardiovascular disease(ASCVD).Red yeast rice(RYR)is a nutraceutical widely used as a lipid-lowering dietary supplement.The main cholesterol-lower agents in RYR are monacolins,particularly monacolin K,a weak reversible inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase,whose daily consumption(up to 10 mg/day)reduces LDL-C plasma levels up to 34%within 6-8 weeks when compared to placebo.The reduction in LDL-C is often accompanied by lower levels of plasma apolipoprotein B,total cholesterol,matrix metalloproteinases 2 and 9,high-sensitivity C-reactive protein,non-high-density lipoprotein cholesterol,and blood pressure.RYR has also demonstrated favorable reductions of up to 45%compared to placebo in the risk of ASCVD events in secondary prevention studies.The mechanism of action is similar to statins.When consumed appropriately,RYR is associated with only minimal side effects.Mild myalgia may be seen in patients who cannot tolerate low-dose statins.In individuals with no additional ASCVD risk factors,RYR is a safe and effective supplement in treating mild to moderate hyperlipidemia.
文摘Background Coronary artery calcification(CAC),a hallmark of atherosclerosis,paradoxically associates with reduced cardiovascular risk under statin therapy despite accelerated calcification progression,prompting this study to explore CAC metrics as potential mediators between statin use and major adverse cardiovascular events(MACE).Methods Clinical data of 246 hospitalized patients who underwent coronary computed tomography angiography(CCTA)at Guangdong Provincial People's Hospital from January 2023 to June 2023 were retrospectively analyzed.Linear regression was used to evaluate the relationship between statin use and CAC parameters.Multivariable Poisson regression models were applied to explore the associations of statin use and CAC parameters with MACE risk.A mediation analysis was performed to assess the role of CAC parameters in the statin-MACE relationship.Results Statin use was independently associated with increased calcification score(β=0.648,P<0.001),CAC volume(β=0.623,P<0.001),and calcified plaque proportion(β=0.606,P=0.002).Multivariable Poisson regression indicated that statin use significantly reduced MACE risk[incidence rate ratio(IRR):0.33,P=0.018],whereas calcification score(IRR:2.63,P=0.026)and CACvolume(IRR:2.66,P=0.044)were associated with elevated MACE risk;Calcified plaque proportion showed no significant association.Mediation analysis revealed that calcification score(β=0.035,P=0.021)and CAC volume(β=0.023,P=0.018)exerted masking effects,while calcified plaque proportion had no mediating role.Conclusions Calcification score and CACvolume demonstrated limited masking effects in the association between statin use and MACE.
文摘BACKGROUND The pleiotropic effects of statins,including anti-inflammatory and immunomodulatory actions,have prompted investigation into their perioperative role in colorectal cancer(CRC)surgery.However,findings remain inconsistent due to heterogeneity in study designs,statin regimens,and outcome definitions.This reviews current observational evidence,emphasizing the duration of statin therapy and its association with postoperative outcomes.AIM To evaluate the association between statin therapy and postoperative outcomes in patients undergoing CRC surgery.METHODS A systematic literature search was conducted using PubMed and Google Scholar through March 2025.Five cohort studies evaluating statin use in CRC surgery were included.Primary outcomes assessed included anastomotic leak,surgical site infection,and 30-day and 90-day mortality.Data on statin duration and confounders such as comorbidities and surgical variables were also extracted.RESULTS Three studies investigated the rates of anastomotic leaks in patients who used statins compared to those who did not.Two of the studies found no significant difference,while one noted a marginally higher leak rate among statin users.Diabetes,smoking habits,and operative time were found to be common confounding factors.Conversely,the use of statins was consistently linked to a decrease in 30-day mortality in propensity-matched groups,although findings regarding 90-day mortality were variable.CONCLUSION Statin therapy may confer short-term survival benefits in CRC surgical patients,potentially via anti-inflammatory or cytoprotective mechanisms.While evidence regarding anastomotic leaks remains inconclusive,trends suggest improved postoperative outcomes.These findings are constrained by methodological heterogeneity,underscoring the need for prospective,randomized studies to confirm benefits and identify optimal patient subgroups.
基金National Key Research and Development Program of China(2017YFC1700502)Ministry of Science and Technology of China。
文摘Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo(TXL)capsule to treat atherosclerosis.However,clinical evidence of the effects of TXL treatment on coronary plaque vulnerability is unavailable.In response,we developed this study to investigate the hypothesis that on the basis of statin therapy,treatment with TXL capsule may stabilize coronary lesions in patients with acute coronary syndrome(ACS).The TXL-CAP study was an investigator-initiated,randomized,double-blind clinical trial conducted across 18 medical centers in China.Patients with ACS aging from 18 to 80 years old who had a non-intervened coronary target lesion with a fibrous cap thickness(FCT)<100μm and lipid arc>90°as defined by optical coherence tomography(OCT)were recruited.A total of 220 patients who met the selection criteria but did not meet the exclusion criteria will be finally recruited and randomized to receive treatment with TXL(n=110)or placebo(n=110)for a duration of 12 months.The primary endpoint was the difference in the minimum FCT of the coronary target lesion between TXL and placebo groups at the end of the 12-month follow-up.Secondary endpoints included:(1)changes of the maximum lipid arc and length of the target plaque,and the percentage of lipid,fibrous,and calcified plaques at the end of the12-month period;(2)the incidence of composite cardiovascular events and coronary revascularization within the 12 months;(3)changes in the grade and scores of the angina pectoris as assessed using the Canadian Cardiovascular Society(CCS)grading system and Seattle angina questionnaire(SAQ)score,respectively;and(4)changes in hs-CRP serum levels.The results of the TXLCAP trial will provide additional clinical data for revealing whether TXL capsules stabilizes coronary vulnerable plaques in Chinese ACS patients.
文摘Metabolic-associated steatotic liver disease(MASLD)is a global health burden intricately linked to cardiovascular disease(CVD)through shared pathways-insulin resistance,dyslipidemia,and chronic inflammation.CVD has become the leading cause of mortality in MASLD,necessitating integrated management strategies.This review synthesizes evidence on bidirectional MASLD-CVD interactions and evaluates therapeutic approaches:Lifestyle modifications,pharmacotherapy(e.g.,GLP-1 receptor agonists,SGLT2 inhibitors,statins),and metabolic interventions.Despite progress,critical gaps persist in risk stratification tools,personalized treatment algorithms,and long-term outcomes of novel agents like resmetirom.A multidisciplinary care model,bridging hepatology and cardiology,is essential to address these challenges and improve patient outcomes.
文摘Background: To study the influence of blood lipid levels on hemorrhagic transformation(HT) and prognosis after acute cerebral infarction(ACI).Methods: Patients with ACI within 72 h of symptoms onset between January 1 st, 2015, and December 31 st, 2016, were retrospectively analyzed. Patients were divided into group A(without HT) and group B(HT). The outcomes were assessed after 3 months of disease onset using the modified Rankin Scale(m RS). An m RS score of 0–2 points indicated excellent prognosis, and an m RS score of 3–6 points indicated poor prognosis.Results: A total of 732 patients conformed to the inclusion criteria, including 628 in group A and 104 in group B. The incidence of HT was 14.2%, and the median onset time was 2 d(interquartile range, 1–7 d). The percentages of patients with large infarct size and cortex involvement in group B were 80.8% and 79.8%, respectively, which were both significantly higher than those in group A(28.7 and 33.4%, respectively). The incidence rate of atrial fibrillation(AF) in group B was significantly higher than that in group A(39.4% vs. 13.9%, P<0.001). The adjusted multivariate analysis results showed that large infarct size, cortex involvement and AF were independent risk factors of HT, while total cholesterol(TC) was a protective factor of HT(OR=0.359, 95% CI 0.136–0.944, P=0.038). With every 1 mmol/L reduction in normal TC levels, the risk of HT increased by 64.1%. The mortality and morbidity at 3 months in group B(21.2% and 76.7%, respectively) were both significantly higher than those in group A(8.0% and 42.8%, respectively). The adjusted multivariate analysis results showed that large infarct size(OR=12.178, 95% CI 5.390–27.516, P<0.001) was an independent risk factor of long-term unfavorable outcomes, whereas low-density lipoprotein cholesterol(LDL-C) was a protective factor(OR=0.538, 95% CI 0.300–0.964, P=0.037). With every 1 mmol/L reduction in normal LDL-C levels, the risk of an unfavorable outcome increased by 46.2%. Major therapies, including intravenous recombinant human tissue plasminogen activator(r TPA), intensive lipid-lowering statins and anti-platelets, were not significantly related to either HT or long-term, post-ACI poor prognosis.Conclusions: For patients with large infarct sizes, especially those with cortex involvement, AF, or lower levels of TC, the risk of HT might increase after ACI. The risk of a long-term unfavorable outcome in these patients might increase with a reduction in LDL-C.
文摘3-Hydroxy-3-methylglutaryl coenzyme A （HMG CoA） reductase produces mevalonate, an important intermediate in the synthesis of cholesterol and essential nonsterol isoprenoids. The reductase is subject to an exorbitant amount of feedback control through multiple mechanisms that are mediated by sterol and nonsterol end-products of mevalonate metabolism. Here, I will discuss recent advances that shed light on one mechanism for control of reductase, which involves rapid degradation of the enzyme. Accumulation of certain sterols triggers binding of reductase to endoplasmic reticulum （ER） membrane proteins called Insig-1 and Insig-2. Reductase-Insig binding results in recruitment of a membrane-associated ubiquitin ligase called gp78, which initiates ubiquitination of reductase. This ubiquitination is an obligatory reaction for recognition and degradation of reductase from ER membranes by cytosolic 26S proteasomes. Thus, sterol-accelerated degradation of reductase represents an example of how a general cellular process （ER-associated degradation） is used to control an important metabolic pathway （cholesterol synthesis）.
基金Supported by The Division of Integrative Systems Medicine and Digestive Disease at Imperial College London receives financial support from the National Institute for Health Research(NIHR)Imperial Biomedical Research Centre(BRC)based at Imperial College Healthcare NHS Trust and Imperial College Londonfunded by the NIHR BRC
文摘Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis.This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications,together with discussion of current controversies and potential future directions.PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety,efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis.Non-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices,but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation.Recent observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation.The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy;recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis.Diuretics remain the mainstay of uncomplicated ascites treatment,and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites.Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications.Despite initial hepatotoxicity concerns,safety of statin administration has been demonstrated in compensated cirrhosis.Furthermore,statins are suggested to have protective effects upon fibrosis progression,decompensation and mortality.Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting.Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis,and may impede hepatic fibrogenesis and decompensation.Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management,nutritional optimisation and patient education.
文摘Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen species (ROS), altered redox state, and elevated oxidant stress have been demonstrated in the lungs and RV of several animal models of PH, including chronic hypoxia, monocrotaline toxicity, caveolin-1 knock-out mouse, and the transgenic Ren2 rat which overexpresses the mouse renin gene. Generation of ROS in these models is derived mostly from the activities of the nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase. As disease progresses circulating monocytes and bone marrow-derived monocytic progenitor cells are attracted to and accumulate in the pulmonary vasculature. Once established, these inflammatory cells generate ROS and secrete mitogenic and fibrogenic cytokines that induce cell proliferation and fibrosis in the vascular wall resulting in progressive vascular remodeling. Deficiencies in antioxidant enzymes also contribute to pulmonary hypertensive states. Current therapies were developed to improve endothelial function, reduce pulmonary artery pressure, and slow the progression of vascular remodeling in the pulmonary vasculature by targeting deficiencies in either NO (PDE-type 5 inhibition) or PGI 2 (prostacyclin analogs), or excessive synthesis of ET-1 (ET receptor blockers) with the intent to improve patient clinical status and survival. New therapies may slow disease progression to some extent, but long term management has not been achieved and mortality is still high. Although little is known concerning the effects of current pulmonary arterial hypertension treatments on RV structure and function, interest in this area is increasing. Development of therapeutic strategies that simultaneously target pathology in the pulmonary vasculature and RV may be beneficial in reducing mortality associated with RV failure.
文摘We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a greater potential compared with other statins to damage the liver is unclear and the involved mechanisms are also unknown. However, rosuvastatin is taken up by hepatocytes more selectively and more efficiently than other statins, and this may reasonably represent an important variable to explain the hepatotoxic potential of rosuvastatin. Our report supports the view that a clinically significant risk of liver toxicity should be considered even when rosuvastatin is given at the range of doses used in common clinical practice.
基金Supported by A United States National Cancer Institute Grant,No.R01CA117895a grant from the Duncan Family Institute for Cancer Prevention and Risk Assessment,UT MDAnderson Cancer Center
文摘AIM:To determine the effects of curcumin,(-)-epigallocatechin-3-gallate (EGCG),lovastatin,and their combinations on inhibition of esophageal cancer.METHODS:Esophageal cancer TE-8 and SKGT-4 cell lines were subjected to cell viability methyl thiazolyl tetrazolium and tumor cell invasion assays in vitro and tumor formation and growth in nude mouse xenografts with or without curcumin,EGCG and lovastatin treatment.Gene expression was detected using immunohistochemistry and Western blotting in tumor cell lines,tumor xenografts and human esophageal cancer tissues,respectively.RESULTS:These drugs individually or in combinations significantly reduced the viability and invasion capacity of esophageal cancer cells in vitro.Molecularly,these three agents reduced the expression of phosphorylated extracellular-signal-regulated kinases (Erk1/2),c-Jun and cyclooxygenase-2 (COX-2),but activated caspase 3 in esophageal cancer cells.The nude mouse xenograft assay showed that EGCG and the combinations of curcumin,EGCG and lovastatin suppressed esophageal cancer cell growth and reduced the expression of Ki67,phosphorylated Erk1/2 and COX-2.The expression of phosphorylated Erk1/2 and COX-2 in esophageal cancer tissue specimens was also analyzed using immunohistochemistry.The data demonstrated that 77 of 156 (49.4%) tumors expressed phosphorylated Erk1/2 and that 121 of 156 (77.6%) esophageal cancers expressed COX-2 protein.In particular,phosphorylated Erk1/2 was expressed in 23 of 50 (46%) cases of esophageal squamous cell carcinoma (SCC) and in 54 of 106 (50.9%) cases of adenocarcinoma,while COX-2 was expressed in 39 of 50 (78%) esophageal SCC and in 82 of 106 (77.4%) esophageal adenocarcinoma.CONCLUSION:The combinations of curcumin,EGCG and lovastatin were able to suppress esophageal cancer cell growth in vitro and in nude mouse xenografts,these drugs also inhibited phosphorylated Erk1/2,c-Jun and COX-2 expression.
文摘Hyperlipidemia is a well-established risk factor for developing cardiovascular disease(CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors(statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein(LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsinkexin type 9(PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.
基金Supported by (in part) research grants from the Italian Ministry of University and Research (No. FIRB 2003 RBAU01RANB002)the Italian National Research Council (short-term mobility grant 2005)+2 种基金the University of Bari (grants No. ORBA09XZZT and No. ORBA08YHKX) (to Portincasa P)University of Bari (No. DR11598-2009)the National Institutes of Health (US Public Health Service) (research grants No. DK54012 and No. DK73917) (to Wang DQH)
文摘Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones,new perspectives regarding medical therapy of cholelithiasis are currently under discussion,also taking into account the pathogenesis of gallstones,the natural history of the disease and the analysis of the overall costs of therapy.A careful selection of patients may lead to successful nonsurgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones.The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations,suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe),or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis,might be proposed as additional approaches for treating cholesterol gallstones.In this review we discuss old,recent and future perspectives on medical treatment of cholesterol cholelithiasis.
