You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
TNFSF4 gene polymorphism rs3861950 but not rs3850641 is associated with the risk of cerebral infarction in a Chinese population
Abstract 1:
Tumor necrosis factor superfamily member 4 ( TNFSF4 ) plays a key role in the process of atherosclerosis , a common risk factor for both myocardial and cerebral infa rct ions . Recent studies indicate that the single nucleotide polymorphism ( SNP ) rs3850641 in TNFSF4 is associated with higher risk of myocardial infa rct ion , but little is known about the association between TNFSF4 variation and cerebral infa rct ion ( CI ) . A case-control study involving 385 CI patients and 385 age-matched , sex-matched non-CI controls was conducted in a Chinese population , only the most common subtype , atherosclerosis CI , was recruited . Two SNPs of TNFSF4 , rs3850641 and rs3861950 , were genotyped by the TaqMan SNP genotyping method , and verified partly by genomic DNA sequencing . The results revealed a significant allelic association between rs3861950 and CI ( Odds ration = 1.733 , 95 % confidence interval = 1.333–2.254 , P = 0.000 ) . Genotypic association analysis demonstrated that the CC genotype of rs3861950 confers susceptibility to CI ( Odds ration = 2.896 , 95 % confidence interval = 1.368–6.132 ) , and it was associated with a significantly higher risk of ischemic stroke ( Odds ration = 3.520 , 95 % confidence interval = 1.546–8.015 , P = 0.003 ) after adjusting for the other confirmed risk factors such as the history of hypertension , diabetes , CAD , smoking and alcohol drinking . While the odds ratio of the T allele to the C allele was 1.733 ( 95 % confidence interval : 1.333–2.254 ) . However , there was no significant association between rs3850641 and CI ( Odds ration = 1.288 , 95 % confidence interval = 0.993–1.670 , P = 0.056 ) . TNFSF4 gene polymorphism rs3861950 , but not rs3850641 , is associated with the risk of atherosclerosis CI in a Chinese population


Title 2:
T-Cell–Mediated Lysis of Endothelial Cells in Acute Coronary Syndromes
Abstract 2:
Background —CD4 T lymphocytes accumulate in unstable plaque . The direct and indirect involvement of these T cells in tissue injury and plaque instability is not understood . Methods and Results —Gene profiling identified perforin , CD161 , and members of the killer-cell immunoglobulin-like receptors as being differentially expressed in CD4+CD28null T cells , a T-cell subset that preferentially infiltrates unstable plaque . Frequencies of CD161 + and perforin-expressing CD4 T cells in peripheral blood were significantly increased in patients with unstable angina ( UA ) . CD161 appeared on CD4+CD28null T cells after stimulation , suggesting spontaneous activation of circulating CD4 T cells in UA . Perforin-expressing CD4 + T-cell clones from patients with UA exhibited cytotoxic activity against human umbilical vein endothelial cells ( HUVECs ) in redirected cytotoxicity assays after T-cell receptor triggering and also after stimulation of major histocompatibility complex class I – recognizing killer-cell immunoglobulin-like receptors . HUVEC cytolysis was dependent on granule exocytosis , as demonstrated by the paralyzing effect of pretreating CD4+CD28null T cells with strontium . Incubation of HUVECs with C-reactive protein ( CRP ) increased HUVEC lysis in a dose-dependent fashion . Conclusions —In patients with UA , CD4 T cells undergo a change in functional profile and acquire cytotoxic capability . Cytotoxic CD4 T cells effectively kill endothelial cells ; CRP sensitizes endothelial cells to the cytotoxic process . We propose that T-cell – mediated endothelial cell injury is a novel pathway of tissue damage that contributes to plaque destabilization . The sensitizing effect of CRP suggests synergy between dysregulated T-cell function and acute phase proteins in acute coronary syndromes


Title 3:
Genetic variants of tumor necrosis factor superfamily, member 4 (TNFSF4), and risk of incident atherothrombosis and venous thromboembolism.
Abstract 3:
BACKGROUND Recent data have implicated tumor necrosis factor ( lig and ) superfamily , member 4 ( TNFSF4 ) gene variation in myocardial infa rct ion in women ; however , no prospect i ve data are available on either incident arterial or venous disorders . METHODS We evaluated 2 previously characterized TNFSF4 gene variants ( -921C > T and dbSNP rs3850641 ) with a ) incident arterial events  using a prospect i ve case-cohort design with 344 incident CVD cases and 2254 control participants , all white , drawn from the Women 's Health Study cohort with 10 years of follow-up , and b )  venous thromboembolism ( VTE ) risk using a nested , matched case-control design of 108 white male pairs ( drawn from the Physicians ' Health Study cohort ) and a case-cohort design of white female participants consisting of 125 cases and 2269 controls ( drawn from the Women 's Health Study cohort ) , analyzed separately . RESULTS Genotype distributions were in Hardy-Weinberg equilibrium . Results from a marker-by-marker regression analysis , adjusting for traditional risk factors , showed a significant association of -921C > T with an increased risk of VTE in women ( additive : odds ratio 1.86 ; 95 % CI 1.17 - 2.92 , P = 0.008 ) in women . Furthermore , using a haplotype-based regression analysis , haplotype C-G was associated with a reduced risk of VTE relative to the referent haplotype , C-A ( odds ratio 0.50 ; 95 % CI 0.27 - 0.92 ; P = 0.02 ) . In contrast , we found little evidence for an association of the variants/haplotypes with risk of VTE in men or CVD risk in women ( as previously reported ) . CONCLUSIONS Our present findings , if corroborated in other prospect i ve investigations , suggest that the TNFSF4 variants tested may be useful indicators for assessing the risk of venous thromboembolism


Title 4:
Human genetic evidence that OX40 is implicated in myocardial infarction.
Abstract 4:
We recently showed that genetic variants in OX40L are associated with myocardial infa rct ion ( MI ) and severity of coronary artery disease in human . A number of studies also suggest a possible role for OX40 ( the OX40L receptor ) as a factor contributing to atherosclerosis . In the present study , the OX40 gene was screened for variants associated with precocious MI , using individuals with MI before the age of 60 and controls . Despite the fact that the OX40 gene is highly conserved between species and that relatively few common genetic variants were encountered , an association with MI was seen for a polymorphism in intron 5 ( rs2298212 ) . In silico investigation suggested that genetic variation ( rs2298211 ) , linked to this intronic variant , is possibly affecting spliceosome function . Our results provide evidence that variants in human OX40 might influence susceptibility to MI . The relevance of these findings is supported by the vital functions fulfilled by OX40 in mammals as reflected by the high level of evolutionary conservation
The present study demonstrated that there is no significant relationship between TNFSF4 gene polymorphism and cerebrovascular and cardiovascular diseases