Causal relationship between genetically predicted depression and cancer risk: a two-sample bi-directional mendelian randomization.

BACKGROUND: Depression has been reported to be associated with some types of cancer in observational studies. However, the direction and magnitude of the causal relationships between depression and different types of cancer remain unclear. METHODS: We performed the two-sample bi-directional mendelian randomization with the publicly available GWAS summary statistics to investigate the causal relationship between the genetically predicted depression and the risk of multiple types of cancers, including ovarian cancer, breast cancer, lung cancer, glioma, pancreatic cancer, lymphoma, colorectal cancer, thyroid cancer, bladder cancer, and kidney cancer. The total sample size varies from 504,034 to 729,150. Causal estimate was calculated by inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the causal relationship. RESULTS: After correction for heterogeneity and horizontal pleiotropy, we only detected suggestive evidence for the causality of genetically predicted depression on breast cancer (OR = 1.09, 95% CI: 1.03-1.15, P = 0.0022). The causal effect of depression on breast cancer was consistent in direction and magnitude in the sensitivity analysis. No evidence of causal effects of depression on other types of cancer and reverse causality was detected. CONCLUSIONS: The result of this study suggests a causative effect of genetically predicted depression on specific type of cancer. Our findings emphasize the importance of depression in the prevention and treatment of breast cancer.

Evolving landscape and academic attitudes toward the controversies of global immuno-oncology trials.

This cross-sectional and longitudinal descriptive analysis aimed to track the evolving landscape of global immuno-oncology (IO) trials and provide insight into the resolution of IO-related controversies. Clinical trials (n = 4510) registered on ClinicalTrials.gov in 2007 to 2019 studying immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT), cancer vaccines and immune modulators were included. Most of IO trials are Phase 2 and focus on ICIs and multiple IO therapies. The United States leads global IO research, with stable growth and the best methodological quality. Mainland China ranks first in the number of ACT trials but has the lowest article publication rate (6.2%). A multiple-arm comparative design is often adopted in multiple IO therapies trials (44.0%). Trials studying ICIs and multiple IO therapies are likely to use early registration (80.0% and 86.6%) and stringent corticosteroid-/infection-related criteria. Hospitals have provided the most extensive and strongest support for all IO categories. Big pharma prefers to fund Phase 3-4 ICI trials (6.98%), while small pharma has a wider sponsorship favoring Phase 1-2 trials. The "partial-use-of-corticosteroids" strategy is generally well accepted in ICI trials with a definitive trend (32.5%; P < .001) but is associated with the poor dissemination of results (P ≤ .020), while the complete disclosure and standardization of dose/timing limits are still lacking. Disparities in design features and dissemination of results are widespread in IO trials and are modulated by IO category, cancer type and sponsor. We propose policy reforms to redefine the timely publication of IO trials and standardize the resolution of corticosteroid-/infection-related issues.

[Effect of Kuanxiong aerosol on coronary heart disease angina patients: a multicenter randomized controlled clinical study].

OBJECTIVE: To evaluate the anginal attack-relieving efficacy and safety of Kuanxiong Aerosol (KA) in patients with coronary heart disease (CHD). METHODS: A total of 780 patients confirmatively diagnosed as CHD angina from November 2011 to December 2012 in 13 medical centers in the mainland area were assigned to 2 groups by blocked randomization, the treatment group (376 cases) and the control group (374 cases). When the angina attacked, patients in the treatment group received sublingual spray three times, 0.6 mL each time, while those in the control group sublingually dissolved Nitroglycerin Tablet (NT), 0.5 mg each tablet. The effective rate of angina relief, efficacy of electrocardiogram (ECG), and the incidence of adverse reactions were observed. RESULTS: The 3 min and 5 min remission rates of angina attack were 53.72% (202/376) and 94.41% (355/376) in the treatment group, and 47.86% (179/374) and 90.64% (339/374) in the control group. The 95% confidence interval (CI) of the difference between the 2 groups of 3 min and 5 min remission rates of angina attacks were [(-1.84%, 12.32%) and (-1.33%, 6.85%) respectively, P > 0.05]. The total improvement rates of ST-T changes in the treatment group and the control group after treatment were 74.07% and 73.13% respectively (P > 0.05). The adverse reaction rate was 9.31 (35/376 cases) in the treatment group and 22.46% (84/374 cases) in the control group (P < 0.01). CONCLUSION: KA was not inferior to NT in relieving anginal attacks and improving ischemic ECG changes, and had obviously less adverse reaction.

Metastatic patterns of level II-V cervical lymph nodes assessed per vertebral levels in nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: The current cervical lymph nodes classification system is not perfectly reasonable for radiotherapy of nasopharyngeal carcinoma (NPC). This study aimed to determine the metastatic patterns of level II-V lymph nodes in NPC by using vertebrae as anatomical landmarks. MATERIALS AND METHODS: Four hundred and forty node-positive NPC patients were selected. Metastatic lymph nodes were diagnosed using positron emission tomography/computed tomography scan or magnetic resonance imaging. We evaluated univariate and multivariate logistic correlations between the vertebral levels of metastatic level II-V lymph nodes. RESULTS: The metastasis rate of level II-V lymph nodes gradually decreased from C2 (66.5%) and C3 (68.2%) to T1 (4.1%) vertebral levels. When assessed per vertebral level, 98.4% were non-skip metastasis. The interval of vertebral levels and distance between the inferior border of the tumor and the metastatic lymph nodes were similar in N1 and N2 patients. Univariate correlation analysis showed the metastasis of level II-V lymph nodes at each vertebral level was associated with the metastasis at any other vertebral level. In the multivariate analysis, metastasis at any one of the C2-C7 vertebral levels strongly and positively correlated with metastasis at two adjacent vertebral levels, including one level above and one below. CONCLUSION: This is the first study to report the distribution and non-skip metastatic patterns of level II-V lymph nodes assessed per vertebral levels in NPC. The low-risk clinical target volume could be reduced to two vertebral levels below the vertebral level of the metastatic level II-V nodes when both imaging modalities are available.

Disparities in positive results and dissemination of randomized controlled trials in immuno-oncology.

BACKGROUND: This cross-sectional and longitudinal analysis aimed to demonstrate the disparities in positive results and dissemination patterns of randomized controlled trials (RCTs) in global immuno-oncology (IO). METHODS: Phase II-IV RCTs with results reported by article publications registered on ClinicalTrials.gov in 2007-2018 studying immune checkpoint inhibitors (ICIs), adoptive cell transfer, cancer vaccines, and immune modulators were included. RESULTS: Twenty-eight percent of trials were positive (72 of 258), most of which were pharma-sponsored and focused on ICI and multiple IO therapies in lung cancer, melanoma, and multiple cancer types. The recent period of trial start year, upfront registration, large sample size, high strictness score on corticosteroid/infection-related criteria, and survival endpoints were associated with positive results. Trials from Mainland China had a faster publication timeline of positive results but lacked study diversity or full reporting of negative results compared with US and multinational trials. Compared with phase II trials, phase III-IV trials had a higher average proportion of positive results (28.9% vs. 22.2%) and a more stable change over the past decade (23.65% vs. 49.24%). Positive trials yielded more secondary manuscripts (10 vs. 4), a shorter publication process of approximately two years (P < 0.001), and a superiority in the dissemination of journals with an h-index >90 (P < 0.001) compared with negative trials. CONCLUSION: Disparities in positive result dissemination are widespread in IO RCTs and affected by trial features. We proposed improvements in upfront registration, procedural integrity, and adequate inclusion of rival trials reporting negative results within the earlier two years in future reviews.

Immuno-oncology (IO) is a novel treatment modality utilizing the natural ability of body's immune system to fight against cancer. The acknowledged standard method to confer the best medical evidence for showing the efficacy of a new intervention is randomized controlled trials (RCTs), and the publication of trial results via journal articles usually modifies medical decisions. A trial labeled negative means that the pre-specified goal was not met, but it deserves more attention rather than a simple interpretation of scientific failure. Previous studies on oncology trials indicated that negative and positive trials have different patterns of result publication and varied trial features. Although IO-related RCTs obtain a continuously increasing number, the extent and tendencies (positive or negative) of their results have not been assessed. To conduct a timely summary and a comprehensive analysis focusing on the publication details and its relationship with the properties of IO trials, we included phase II­IV IO RCTs with results reported by article publications registered on ClinicalTrials.gov in 2007­2018. We found that disparities in positive results and publication are widespread in IO RCTs and severely affected by IO category, cancer type, sponsorship, trial phase, and geographic origin. Positive trials had a significantly shorter publication timeline of approximately two years, more secondary manuscripts, and a superiority in high-quality publications over negative trials. We propose that investigators should complete registration before trial launch, improve procedural integrity, and allow an adequate inclusion of rival trials reporting negative results within the earlier two years in future IO-related reviews.

Development of a prediction model for radiotherapy response among patients with head and neck squamous cell carcinoma based on the tumor immune microenvironment and hypoxia signature.

INTRODUCTION: The immune system and hypoxia are major factors influencing radiosensitivity in patients with different cancer types. This study aimed at developing a model to predict radiotherapy response in patients with head and neck squamous cell carcinoma (HNSCC) based on the tumor immune microenvironment and hypoxia signature. MATERIALS AND METHODS: We first evaluated the hypoxia status and tumor immune microenvironment in the Cancer Genome Atlas (TCGA) cohort by using transcriptomic data. Differentially expressed genes (DEGs) were identified between the "high immunity and low hypoxia" and "low immunity and high hypoxia" groups and those DEGs significantly associated with disease-specific survival in the univariate Cox regression analysis were selected as the prognostic DEGs. We selected the immune hypoxia-related genes (IHRGs) by intersecting prognostic DEGs with immune and hypoxia gene sets. We used the IHRGs to train a multivariate Cox regression model in the TCGA cohort, based on which we calculated the IHRG prognostic index (IHRGPI) for each patient and validated its efficacy in predicting radiotherapy response in the Gene Expression Omnibus cohorts. Furthermore, we explored potential mechanisms and effective combinational treatment strategies for different IHRGPI groups. RESULTS: Five IHRGs were used to construct the IHRGPI, which was used to dichotomize the cohorts. The patients with lower IHRGPI showed a better radiotherapy response across different cohorts and endpoints, including overall survival, progression-free survival, and recurrence-free survival (p < 0.05). Patients with higher IHRGPI showed greater hypoxia and lesser immune cell infiltration. A lower IHRGPI indicated a better immunotherapy response, while a higher IHRGPI indicated a better chemotherapy response. CONCLUSIONS: IHRGPI is promising for predicting radiotherapy response and guiding combinational treatment strategies in patients with HNSCC.

Development and validation of a joint model for dynamic prediction of overall survival in nasopharyngeal carcinoma based on longitudinal post-treatment plasma cell-free Epstein-Barr virus DNA load.

OBJECTIVES: To develop and validate a joint model for dynamic prediction of overall survival (OS) in nasopharyngeal carcinoma (NPC) based on longitudinal post-treatment plasma cell-free Epstein-Barr virus (cfEBV) DNA load. PATIENTS AND METHODS: We analyzed 695 patients with non-metastatic NPC and detectable post-treatment cfEBV DNA load who did not receive adjuvant therapy. We fitted the trajectories of post-treatment cfEBV DNA load as a function of time into a linear mixed-effect model and fitted a Cox regression model with covariates including age, T and N stages, and lactate dehydrogenase level. Finally, we combined both via joint modeling to develop and validate our dynamic model. RESULTS: A strong positive correlation was found between the individual longitudinal post-treatment cfEBV DNA load and the risk of death from any cause (P < 0.001). We developed a joint model capable of providing subject-specific dynamic prediction of conditional OS based on the evolution of the individual plasma cfEBV DNA load trajectory. The joint model showed reliable performance in both training and validation cohorts, with a large area under the curve (interquartile range [IQR]: training cohort, 0.775-0.850; validation cohort, 0.826-0.900) and low prediction errors (IQR: training cohort, 0.017-0.078; validation cohort, 0.034 -0.071). An increasing amount of data on cfEBV DNA load was associated with better model performance. CONCLUSION: Our model provided reliable subject-specific dynamic prediction of conditional OS, which could help guide individualized post-treatment surveillance, risk stratification, and management of NPC in the future.

Progression-free survival assessed per immune-related or conventional response criteria, which is the better surrogate endpoint for overall survival in trials of immune-checkpoint inhibitors in lung cancer: A systematic review and meta-analysis.

Progression-free survival (PFS) has been used as a surrogate endpoint for overall survival (OS) in lung cancer trials. The pattern of response to immune-checkpoint inhibitors (ICIs) differs from that to conventional chemotherapy, so immune-related response evaluation criteria were proposed. This study aims at determining which PFS measure, PFS assessed per immune-related response evaluation criteria (iPFS), or conventional criteria (cPFS), is the better surrogate endpoint for OS in trials of ICIs in lung cancer. We selected clinical trials in lung cancer that administered ICIs to at least one arm and reported both median OS and median PFS from PubMed, Embase, and The Cochrane Library. We compared the correlation between treatment effect (hazard ratio) on OS and cPFS or iPFS and the correlation between median OS and median cPFS or iPFS using weighted linear regression at trial level. We analyzed 78 ICI arms (13,438 patients) from 54 studies, including 66 arms with cPFS, seven arms with iPFS, and five arms with both kinds of PFS. We demonstrated an excellent correlation between treatment effect (hazard ratio) on OS and iPFS (RWLS2  = 0.91), while the correlation was moderate for cPFS (RWLS2  = 0.38). Similarly, the correlation between median OS and median iPFS was also strong (RWLS2 ranging from 0.86 to 0.96) across different phases of trials and different types of lung cancer, ICI, and treatment modalities, while it was much weaker for median cPFS (RWLS2 ranging from 0.28 to 0.88). In conclusion, iPFS provides better trial-level surrogacy for OS than cPFS in trials of ICIs in lung cancer.

Assessment of Modifiable Factors for the Association of Marital Status With Cancer-Specific Survival.

Importance: Married patients with cancer have better cancer-specific survival than unmarried patients. Increasing the early diagnosis and definitive treatment of cancer among unmarried patients may reduce the survival gap. Objectives: To evaluate the extent to which marriage is associated with cancer-specific survival, stage at diagnosis, and treatment among patients with 9 common solid cancers and to recommend methods for reducing the survival gap. Design, Setting, and Participants: This retrospective, population-based cohort study included patients older than 18 years who were diagnosed with 1 of 9 common cancers between January 1, 2007, and December 31, 2016. Patient data were retrieved from the Surveillance, Epidemiology, and End Results Program. Statistical analyses were performed from August 1 to October 1, 2020. Exposures: Marital status, classified as married and unmarried (including single, separated, divorced, widowed, and unmarried patients or domestic partners). Main Outcomes and Measures: The primary outcome was the time ratio (TR) of cancer-specific survival (married vs unmarried). Mediation analyses were conducted to determine the extent to which the association of marriage with cancer-specific survival was mediated by stage at diagnosis and treatment. Results: This study included 1 733 906 patients (894 379 [51.6%] women; 1 067 726 [61.6%] married; mean [SD] age, 63.76 [12.60] years). Multivariate analyses found that those who were married were associated with better cancer-specific survival than unmarried patients (TR, 1.36; 95% CI, 1.35-1.37). Early diagnosis in breast cancer, colorectal cancer, endometrial cancer, and melanoma mediated the association between marital status and cancer-specific survival (breast cancer: proportion mediated [PM], 11.4%; 95% CI, 11.2%-11.6%; colorectal cancer: PM, 10.9%; 95% CI, 10.7%-11.2%; endometrial cancer: PM, 12.9%; 95% CI, 12.5%-13.3%; melanoma: PM, 12.0%; 95% CI, 11.7-12.4%). Surgery mediated the association between marital status and cancer-specific survival in lung (PM, 52.2%; 95% CI, 51.9%-52.4%), pancreatic (PM, 28.9%; 95% CI, 28.6%-29.3%), and prostate (PM, 39.3%; 95% CI, 39.0%-39.6%) cancers. Chemotherapy mediated the association of marital status with cancer-specific survival in lung (PM, 37.7%; 95% CI, 37.6%-37.9%) and pancreatic (PM, 28.6%; 95% CI, 28.4%-28.9%) cancers. Improved cancer-specific survival associated with marriage was greater among men than women (men: TR, 1.27; 95% CI, 1.25-1.28; women: TR, 1.20; 95% CI, 1.19-1.21). The contribution of receiving an early diagnosis and treatment with surgery or chemotherapy to the association between marital status and cancer-specific survival was greater among men than women (early diagnosis: PM, 21.7% [95% CI, 21.5%-21.9%] vs PM, 20.3% [95% CI, 20.2%-20.4%]; surgery: PM, 26.6% [95% CI, 26.4%-26.7%] vs PM, 11.1% [95% CI, 11.0%-11.2%]; chemotherapy: PM, 6.8% [95% CI, 6.7%-6.8%] vs PM, 5.1% [95% CI, 5.0%-5.2%]). Conclusions and Relevance: In this study, survival disparities associated with marital status were attributable to early diagnosis in breast, colorectal, and endometrial cancers as well as melanoma and to treatment-related variables in lung, pancreatic, and prostate cancers. The findings also suggest that marriage may play a greater protective role in the cancer-specific survival of men than of women.

Treatment effects of cumulative cisplatin dose during radiotherapy following induction chemotherapy in nasopharyngeal carcinoma: propensity score analyses.

BACKGROUND: The treatment effects of cumulative cisplatin dose (CCD) during radiotherapy (RT) following induction chemotherapy (IC) have not been determined for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS: A total of 3460 patients with locoregionally advanced NPC who were treated with IC plus cisplatin-based concurrent chemoradiotherapy or RT alone were included in this retrospective study. Three CCD groups (0 mg/m2 ⩽ CCD <100 mg/m2, 100 mg/m2 ⩽ CCD <200 mg/m2, CCD ⩾200 mg/m2) were balanced through the inverse probability of treatment weighting based on propensity scores estimated by a general boosted model. The primary endpoint was overall survival (OS); the secondary endpoints were distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LRFS). RESULTS: CCD ⩾200 mg/m2 and <200 mg/m2 exhibited similar treatment effects for OS and DMFS, and were both superior to CCD <100 mg/m2 for OS and DMFS in patients with stage IVa NPC. The three CCD groups achieved similar treatment effects for patients with stage II-III NPC. After IC, CCD during RT appeared to exert little treatment effect on LRFS. CONCLUSION: The CCD during RT exerts treatment effects and improves OS by reducing the risk of distant metastasis for patients with stage IVa NPC following IC, and CCD <200 mg/m2 (mainly 160 mg/m2 in this group) is recommended. However, RT alone may be sufficient after IC in patients with stage II-III NPC.

Zoonotic parasites carried by invasive alien species in China.

BACKGROUND: The invasive alien species may lead to great environmental and economic crisis due to its strong capability of occupying the biological niche of native species and altering the ecosystem of the invaded area. However, its potential to serve as the vectors of some specific zoonotic pathogens, especially parasites, has been neglected. Thus, the damage that it may cause has been hugely underestimated in this aspect, which is actually an important public health problem. This paper aims to discuss the current status of zoonotic parasites carried by invasive alien species in China. MAIN BODY: This review summarizes the reported zoonotic parasites carried by invasive alien species in China based on the Database of Invasive Alien Species in China. We summarize their prevalence, threat to human health, related reported cases, and the roles of invasive alien species in the life cycle of these parasites, and the invasion history of some invasive alien species. Furthermore, we sum up the current state of prevention and control of invasive alien species in China, and discuss about the urgency and several feasible strategies for the prevention and control of these zoonoses under the background of booming international communications and inevitable globalization. CONCLUSIONS: Information of the zoonotic parasites carried by invasive alien species neither in China or worldwide, especially related case reports, is limited due to a long-time neglection and lack of monitoring. The underestimation of their damage requires more attention to the monitoring and control and compulsory measures should be taken to control the invasive alien species carrying zoonotic parasites.

Effect of Kuanxiong Aerosol () on Patients with Angina Pectoris: A Non-inferiority Multi-center Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris. METHODS: Block randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina. RESULTS: The 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01). CONCLUSIONS: KA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).

Protective effects of isorhamnetin on apoptosis and inflammation in TNF-α-induced HUVECs injury.

Little is known about the role of isorhamnetin on endothelial cell apoptosis and inflammation when insulted by TNF-α injury. In our study, HUVECs were treated with TNF-α for 6 hours. HUVECs apoptosis were detected using flow cytometry. The expressions of ICAM-1, VCAM-1, E-selectin, NF-κB, AP-1 and eNOS were determined with western blotting or flow cytometry. The results showed TNF-α increased of apoptosis and the expression of ICAM-1, VCAM-1 and E-selectin in HUVECs, accompanied by significant augmentation of NF-κB and AP-1 expression. Pretreatment with isorhamnetin significantly reduced apoptosis in TNF-α-treated HUVECs. Moreover, isorhamnetin significantly attenuated TNF-α-induced upregulation of ICAM-1, VCAM-1, AP-1, E-selectin and NF-κB expression. Meanwhile, isorhamnetin also increased the expression of eNOS. So, isorhamnetin could suppress TNF-α-induced apoptosis and inflammation by blocking NF-κB and AP-1 signaling in HUVECs, which might be one of the underlying mechanisms for treatment of coronary heart disease.

Apoptosis of bone marrow mesenchymal stem cells caused by hypoxia/reoxygenation via multiple pathways.

The irreversible loss of cardiomyocytes remains a key problem to resolve, which forms the cellular basis of cardiac dysfunction. MSCs transplantation brings out a promising potential for myocardial renovation with less limitations. However, this cell transplantation therapy is limited by its poor viability after transplantation. Apoptosis is thought to be the major factor that affects the efficiency of MSCs transplantation. Therefore, exploring the process of apoptosis and the underlying mechanisms of MSCs in the 'harmful' microenvironment is significant for the sake of improving the efficiency of MSCs transplantation therapy. A hypoxia/reoxygenation (H/R) model of MSCs had been established. TUNEL, Hoechst staining and MTT were used for the evaluation of morphological changes, cell viability and apoptosis. Mitochondrial transmembrane potential was detected by JC-1 using the fluorescence microscopy system. The protein expression of cytochrome c, p-ERK, p-AKT, Bcl-2, Bax, p-JNK, HIF-1α and VEGF was assessed for the analysis of protein changes using the Western blot. In our study, H/R insult lead to apoptosis and cell viability lost in a time-dependent manner in MSCs. Multiple pathways were involved in the apoptosis of MSCs, including cytochrome c released from mitochondria to cytosol, mitochondrial transmembrane potential lost. In addition, p-ERK and p-AKT were downregulated, while Bcl-2, p-JNK and VEGF were upregulated. H/R induced the apoptosis in MSCs is through multiple pathways. These multiple pathways will be helpful for understanding and explaining the process and mechanism of apoptosis in MSCs.

Short-term pretreatment with atorvastatin attenuates left ventricular dysfunction, reduces infarct size and apoptosis in acute myocardial infarction rats.

BACKGROUND: Atorvastatin showed a number of cardiovascular benefits, however, the role and underlying molecular mechanisms of short-term atorvastatin-mediated protection remain unclear. METHODS: 30 rats were randomly divided into 3 groups: sham group, acute myocardial infarction model group and atorvastatin group. The rats of acute myocardial infarction model were established by ligation of the left anterior descending of coronary arteries. Before surgery, rats in the atorvastatin group received 20 mg/kg/d atorvastatin for 7 days in atorvastatin group. After 4 hours of model established, changes in hemodynamics parameters were recorded and myocardial infarct size was achieved by Evans blue-TTC staining. Myocardium apoptosis was evaluated by TUNEL. The expression of FAS, FAS-L, Bcl-2, Bax, p-BAD, Caspase-8 and Caspase-3 in myocardium were examined by Western blot. RESULTS: In the atorvastatin group, left ventricular function was elevated and infarct size was decreased compared with the model group. Moreover, in the atorvastatin group, the cell apoptosis index was reduced in response to myocardial infarction. The expressions of Bcl-2 were increased and Bax, p-BAD, Fas, Fas-L, caspase-8 and caspase-3 in myocardium were decreased in atorvastatin group. CONCLUSIONS: Short-term atorvastatin pretreatment restored left ventricular function and limited infarct size in acute myocardial infarction, which were associated with reduction of the apoptosis in myocardium through Bcl-2 and Fas pathway.