Advancing predictive markers in lung adenocarcinoma: A machine learning-based immunotherapy prognostic prediction signature.

The prognosis of lung adenocarcinoma (LUAD) is generally poor. Immunotherapy has emerged as a promising therapeutic modality, demonstrating remarkable potential for substantially prolonging the overall survival of individuals afflicted with LUAD. However, there is currently a lack of reliable signatures for identifying patients who would benefit from immunotherapy. We conducted a comparative analysis of two immunotherapy cohorts (OAK and POPLAR) and utilized single-factor COX regression to identify genes that significantly impact the prognosis of LUAD. Based on the TCGA-LUAD dataset, we employed a combination of 101 machine learning algorithms to construct a model and selected the optimal model. The model was validated on five GEO datasets and compared with 144 previously published signatures to assess its performance. Subsequently, we explored the underlying biological mechanisms through tumor mutation burden analysis, enrichment analysis, and immune infiltration analysis. An immunotherapy prognostic prediction signature (IPPS) was constructed based on 13 genes, showing robust performance in the TCGA-LUAD dataset. IPPS exhibited consistent predictive accuracy in the validation cohorts. Compared to 144 previously published signatures, IPPS consistently ranked among the top in terms of C-index values. Further exploration revealed differences between high and low-IPPS groups in terms of tumor mutation burden, pathway enrichment, and immune infiltration. IPPS demonstrates strong predictive capabilities for the prognosis of LUAD patients, offering the potential to identify suitable candidates for immunotherapy and contribute to precision treatment strategies for LUAD.

Impact of oil price volatility and economic policy uncertainty on business investment - Insights from the energy sector.

This research employs a worldwide sample of 4017 energy sector companies from 1996 to 2022 to examine the effects of economic policy uncertainty (EPU) and oil price uncertainty (OPU) on corporate investment in oil/energy sector and this study analyze how market instability and international economic disasters shape the connection between OPU and business assets. GLM regression with firms-years fixed effects and firm-based clustering indicate that both OPU and EPU had a detrimental influence on corporate investment in energy sector. Generalized linear models provide a universal method for addressing various response modeling issues. It is also revealed that oil-producing nations experience OPU and EPU's negative effects more severely than oil-consuming nations. This paper also demonstrates that the link between corporate investment, OPU and EPU is influenced by nations that produce oil, market volatility, and global financial crises. Strong evidence was found supporting the notion that OPU and EPU had a statistically significant detrimental impact on business assets. The findings of the paper are consistent under a variety of robustness tests and show that the association between OPU and EPU and business assets still holds. The results have significant bearing on the asset strategies that company managers and governments should adopt in light of the volatility of oil prices and EPU and this study provide valuable insights for policymakers who are focused on achieving energy transition, enhancing energy security, and meeting environmental goals such as reducing greenhouse gas emissions.

Recurrence of common bile duct stones after choledocholithotomy in elderly patients: risk factor analysis and clinical prediction model development.

Background: The reasons for the recurrence of common bile duct stones (CBDS) in elderly patients after choledocholithotomy are still unclear. This study aims to establish a prediction model for CBDS recurrence by identifying risk factors. Methods: We conducted a retrospective analysis of 1804 elderly patients aged 65 years and above who were diagnosed to have CBDS and were admitted to Nanjing First Hospital between January 1, 2010, and January 1, 2021. According to inclusion and exclusion criteria, 706 patients were selected for the final analysis. The patients were assigned to two groups according to the presence or absence of CBDS recurrence, and their clinical data were then statistically analyzed. Subsequently, a prediction model and nomogram were developed, evaluating effectiveness using the concordance index (C-index). Results: Of the 706 elderly patients, 62 patients experienced CBDS recurrence after surgery, resulting in a recurrence rate of 8.8%. The multivariate Cox analysis showed that prior history of cholecystectomy (hazard ratio [HR] = 1.931, 95% confidence interval [CI]: 1.051-3.547, p = 0.034), white blood cell (WBC) count ≥11.0 × 109/L (HR = 2.923, 95% CI: 1.723-4.957, p < 0.001), preoperative total bilirubin (TBIL) level ≥ 36.5 mmol/L (HR = 2.172, 95% CI: 1.296-3.639, p = 0.003), number of stones ≥2 (HR = 2.093, 95% CI: 1.592-5.294, p = 0.001), maximum stone diameter ≥ 0.85 cm (HR = 1.940, 95% CI: 1.090-3.452, p = 0.024), and T-tube drainage (HR = 2.718, 95% CI: 1.230-6.010, p = 0.013) were independent risk factors of CBDS recurrence in elderly patients after choledocholithotomy. A postoperative CBDS recurrence prediction model was constructed with a C-index value of 0.758 (95% CI: 0.698-0.818) and internal validation value of 0.758 (95% CI: 0.641-0.875). Conclusion: A history of cholecystectomy, WBC count ≥11.0 × 109/L, preoperative TBIL level ≥ 36.5 mmol/L, number of stones ≥2, maximum stone diameter ≥ 0.85 cm, and T-tube drainage are the independent risk factors of CBDS recurrence after choledocholithotomy in elderly patients. Our developed prediction model for CBDS recurrence has good predictive ability and can help predict the prognosis of patients with CBDS.

Deciphering Treg cell roles in esophageal squamous cell carcinoma: a comprehensive prognostic and immunotherapeutic analysis.

Background: Esophageal squamous cell carcinoma (ESCC) is a prevalent and aggressive form of cancer that poses significant challenges in terms of prognosis and treatment. Regulatory T cells (Treg cells) have gained attention due to their influential role in immune modulation within the tumor microenvironment (TME). Understanding the intricate interactions between Treg cells and the tumor microenvironment is essential for unraveling the mechanisms underlying ESCC progression and for developing effective prognostic models and immunotherapeutic strategies. Methods: A combination of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq analysis was utilized to explore the role of Treg cells within the TME of ESCC. The accuracy and applicability of the prognostic model were assessed through multi-dimensional evaluations, encompassing an examination of the model's performance across various dimensions, such as the mutation landscape, clinical relevance, enrichment analysis, and potential implications for immunotherapy strategies. Results: The pivotal role of the macrophage migration inhibitory factor (MIF) signaling pathway within the ESCC TME was investigated, with a focus on its impact on Treg cells and other subpopulations. Through comprehensive integration of bulk sequencing data, a Treg-associated signature (TAS) was constructed, revealing that ESCC patients with elevated TAS (referred to as high-TAS individuals) experienced significantly improved prognoses. Heightened immune infiltration and increased expression of immune checkpoint markers were observed in high-TAS specimens. The model's validity was established through the IMvigor210 dataset, demonstrating its robustness in predicting prognosis and responsiveness to immunotherapy. Heightened therapeutic benefits were observed in immune-based interventions for high-TAS ESCC patients. Noteworthy differences in pathway enrichment patterns emerged between high and low-TAS cohorts, highlighting potential avenues for therapeutic exploration. Furthermore, the clinical relevance of key model genes was substantiated by analyzing clinical samples from ten paired tumor and adjacent tissues, revealing differential expression levels. Conclusion: The study established a TAS that enables accurate prediction of patient prognosis and responsiveness to immunotherapy. This achievement holds significant implications for the clinical management of ESCC, offering valuable insights for informed therapeutic interventions.

Functional Mechanism of MicroRNA-25-3p in Hilar Cholangiocarcinoma Cell Proliferation and Migration Through Regulation of Dual Specificity Phosphatase 5.

OBJECTIVE: Hilar cholangiocarcinoma (HCCA) is a highly aggressive biliary tract tumor. microRNAs (miRs) exert dual actions in various cancers. This paper seeks to expound on the functional mechanisms of miR-25-3p/dual specificity phosphatase 5 (DUSP5) in HCCA cell proliferation and migration. METHODS: HCCA-related data were downloaded from GEO database to screen out differentially-expressed genes. The potential target miR (miR-25-3p) and its expression in HCCA were analyzed on Starbase. The binding relation between miR-25-3p and DUSP5 was confirmed by dual-luciferase assay. Levels of miR-25-3p and DUSP5 in FRH-0201 cells and HIBEpics were determined by RT-qPCR and Western blot. miR-25-3p and DUSP5 levels were intervened with to explore their effects on FRH-0201 cells. The apoptosis, proliferation, migration, and invasion of FRH-0201 cells were evaluated by TUNEL, CCK8, scratch healing, and Transwell assays. Flow cytometry was conducted to assess FRH-0201 cell cycle. Levels of cell cycle-related proteins were determined by Western blot. RESULTS: DUSP5 was weakly-expressed and miR-25-3p was highly-expressed in HCCA samples and cells. miR-25-3p targeted DUSP5. miR-25-3p suppressed FRH-0201 cell apoptosis and increased cell proliferation, migration, and invasion. DUSP5 overexpression partially abrogated miR-25-3p overexpression-exerted effects on FRH-0201 cells. miR-25-3p stimulated G1/S phase transition of FRH-0201 cells by targeting DUSP5. CONCLUSION: miR-25-3p regulated HCCA cell cycle and facilitated cell proliferation and migration by targeting DUSP5.

Exosome-Encapsulated miR-31, miR-192, and miR-375 Serve as Clinical Biomarkers of Gastric Cancer.

In recent years, microRNAs (miRNAs) derived from exosomes have been attracting attention as novel clinical biomarkers in a variety of cancers. In this study, plasma samples from 60 gastric cancer (GC) patients and 63 healthy individuals were collected, and the exosomal microRNAs (ex-miRNAs) were isolated. We determined the specific ex-miRNAs through miRNA microarray and a database of differentially expressed miRNAs called dbDEMC. Then, the expression levels of exosomal miR-31, miR-192, and miR-375 were analyzed by quantitative polymerase chain reaction (qRT-PCR). Compared to the matched controls, exosomal miR-31, miR-375, and miR-192 were significantly upregulated in GC patients. Also, they were found to be associated with gender, with miR-192 being significantly upregulated in male GC patients. Kaplan-Meier analysis indicated that high expressions of exosomal miR-31, miR-375, and miR-192 were positively correlated with poor clinical outcomes of GC patients. Cox univariate and multivariate analysis found that ex-miR-375 expression and TNM stage were independent prognostic factors of overall survival (OS). Our findings revealed that exosomal miR-31, miR-192, and miR-375 might serve as noninvasive, sensitive, and specific biomarkers for the diagnosis and prognosis of GC patients.

Design, Synthesis, and Evaluation of Novel Benzo[d]isoxazole Derivatives as Anticonvulsants by Selectively Blocking the Voltage-Gated Sodium Channel NaV1.1.

Sodium channel blockers are important antiseizure drugs. Since the launch of phenobarbital in 1912, it has a development history of nearly 100 years. However, because of the confounding symptoms, complications, and complex intrinsic pathogenesis of epilepsy, the design and development of blockers specifically targeting sodium channels as antiseizure drugs are difficult and rarely reported. In this study, we designed and synthesized a series of novel benzo[d]isoxazole derivatives as anticonvulsants. Among them, the most potent Z-6b displayed high protection against the MES-induced seizures with an ED50 value of 20.5 mg/kg and a high protective index (TD50/ED50) of 10.3. In addition, Z-6b significantly inhibited NaV1.1 channels in patch-clamp experiments but almost did not inhibit NaV1.2, NaV1.3, and NaV1.6 channels. These findings strongly support the hypothesis that new benzo[d]isoxazole derivatives display anticonvulsant activity by selectively blocking voltage-gated sodium channel NaV1.1, which provides good alternatives for developing selective NaV1.1 channel blockers as antiseizure drugs in the future.

COD/TN ratios shift the microbial community assembly of a pilot-scale shortcut nitrification-denitrification process for biogas slurry treatment.

In this study, effects of carbon to nitrogen (COD/TN) ratios of biogas slurry on shortcut nitrification-denitrification in a pilot-scale integrated fixed film activated sludge (IFAS) system were investigated. Lowering the COD/TN ratio from 11.7 to 6.2 exerted a negative impact on shortcut nitrification-denitrification performance. Accordingly, the NH3-N and TN removal rates decreased from 94.4 to 91.2% and 92.3 to 85.9%, respectively. The dynamics of microbial assembly was analyzed by MiSeq sequencing, and the denitrifying functional genes were quantified by qPCR. The results showed that ammonia oxidizing bacteria and amoA gene were more abundant on the biofilm of oxic tank, indicating they play a key role in NH3-N removal. Autotrophic, endogenous, and fast heterotrophic kinetics denitrifiers were coexisted and enriched in the IFAS system with a decreasing of COD/TN ratio. TN removal was mainly affected by denitrifiers (including Arenimonas, Acidovorax, and Thaurea) harboring narG and nirS genes. Canonical correspondence analysis proved that COD/TN ratio was the most critical factor driving the succession of microbial community. Dissolved oxygen (DO) and pH were found positively correlated with denitrifiers at low COD/TN ratio conditions. As a result, NH3-N and TN removal were effectively enhanced when the DO level in the oxic tank of IFAS system was increased to 1.0-3.0 mg/L.

Synthesis and Evaluation of N-substituted (Z)-5-(Benzo[d][1,3]dioxol-5- ylmethylene)-2-Thioxothiazolidin-4-one Derivatives and 5-Substituted- Thioxothiazolidindione Derivatives as Potent Anticonvulsant Agents.

BACKGROUND: Epilepsy is a serious and common neurological disorder threatening the health of humans. Despite enormous progress in epileptic research, the anti-epileptic drugs present many limitations. These limitations prompted the development of more safer and effective AEDs. METHODS: A series of N-substituted (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)- 2-thioxothiazolidin-4- one derivatives and 5-substituted-thioxothiazolidindione derivatives were designed, synthesized and tested for anticonvulsant activity against maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ). Neurotoxicity was determined by the rotarod test. RESULTS: Among them, the most potent 4e displayed high protection against MES-induced seizures with an ED50 value of 9.7 mg/kg and TD50 value of 263.3 mg/kg, which provided 4e with a high protective index (TD50/ED50) of 27.1 comparable to reference antiepileptic drugs. 4e clearly inhibits the NaV1.1 channel in vitro. The molecular docking study was conducted to exploit the results. CONCLUSION: Stiripentol is a good lead compound for further structural modification. Compound 4e was synthesized, which displayed remarkable anticonvulsant activities, and the NaV1.1 channel inhibition was involved in the mechanism of action of 4e.

MicroRNA-940 inhibits glioma cells proliferation and cell cycle progression by targeting CKS1.

Glioblastoma (GBM) is the most frequently occurred malignant human tumor that arise in brain with a poor prognosis. microRNAs (miRNAs) are vital small molecules during GBM initiation and progression. However, the expression of miR-940 and its potential function in GBM remain poor. Our study demonstrated that miR-940 was dramatically decreased in GBM cells and glioma tissues. Introduction of miR-940 significantly repressed proliferative ability of GBM cells. Notably, treatment of miR-940 dramatically suppressed tumor growth in an animal model, accompanied by decreased Ki67 expression. Functional experiments showed CKS1 as a target of miR-940, knockdown of CKS1 significantly induced the cell cycle arrest and restrained GBM cells proliferation, consistent with miR-940 treatment. Furthermore, reintroduction of CKS1 into glioma cells effectively rescued the tumor suppressive effect of miR-940. Correlation analysis indicated that miR-940 expression was inversely related to CKS1 mRNA levels in NBTs and gliomas. Together, miR-940/CKS1 signaling may be required for GBM progression and provide a new insight in diagnosis and prognosis of GBM patients.

High mobility group box-1 mediates hippocampal inflammation and contributes to cognitive deficits in high-fat high-fructose diet-induced obese rats.

High-fat high-sugar diet-induced obesity can lead to hippocampal inflammation and cognitive deficits, but the detailed underlying mechanism is still not clear. We aim to investigate the role of HMGB1 in hippocampal inflammatory responses and cognitive impairment in high-fat high-fructose diet (HFHFD)-induced obesity. Rats were fed with a normal control diet or an HFHFD diet for 14 weeks. In the last 6 weeks on the diets, the rats were treated with control, or an HMGB1 inhibitor glycyrrhizin, or an anti-HMGB1 neutralizing monoclonal antibody (mAb). Obesity was induced in the HFHFD-fed rats, which had higher body weight, epididymal white adipose tissue (EWAT) weight and caloric efficiency, and lower brain/body weight ratio, glucose tolerance and insulin sensitivity than the ones on normal diets. In the HFHFD-induced obese rats, the HMGB1 levels in plasma and hippocampus were increased, and the nucleus-to-cytoplasm translocation of HMGB1 was promoted. The hippocampal inflammatory responses were enhanced in the HFHFD-induced obesity, including the activation of TLR4 and NF-κB, the production of IL-1ß, TNF-α and IL-6, as well as the activation of microglia and astrocytes. In addition, the hippocampal cell apoptosis and cognitive impairment were observed in the HFHFD-fed rats. The treatment with glycyrrhizin or HMGB1 mAb successfully decreased the HMGB1 levels in plasma and hippocampus, and prevented the HMGB1 translocation from the nucleus to cytoplasm. Inhibiting HMGB1 by glycyrrhizin or HMGB1 mAb suppressed the hippocampal inflammatory, alleviated the apoptosis and ameliorated the cognitive impairment in HFHFD-fed rats. These findings indicate that HMGB1 mediates the hippocampal inflammation and contributes to the cognitive deficits in HFHFD-induced obesity. Therefore, inhibition of HMGB1 may have beneficial effect in protecting against hippocampal inflammation and cognitive deficits in dietary obesity.

Microbial community assembly in detergent wastewater treatment bioreactors: Influent rather than inoculum source plays a more important role.

In this study, three sequencing batch reactors Ra, Rb, Rc with different inoculum sources (activated sludge; activated sludge plus detergent degrading consortium; detergent degrading consortium) were used to treat detergent wastewater [consisting of sodium dodecyl sulfate, polyoxyethylene lauryl ether and tetrasodium ethylenediamine tetraacetate (Na4EDTA)]. Fast start-up and highest performance in phase I and II (organic loading rate were 0.28, 0.39 kgCOD/kgMLSS/d, respectively) were observed in Rc. In contrast, Rb showed highest impact resistance to the increase of EDTA concentration in phase III. High-throughput sequencing analysis showed that inoculum sources led to significant differences on microbial community in phase I. However, regardless of the influent variation in phases II and III, the differences on microbial community among three SBRs were diminished along long-term operation. Pseudomonas, Sphingopyxis, Luteimonas, Pseudoxanthomonas and SM1A02 were found to be the core taxa, they might contribute to the excellent performance of detergent wastewater treatment.

Isolation and Cultivation of Epidermal (Stem) Cells.

Recent studies have shown that epidermal stem cells derived from the epidermis of are able to form hair follicles in the presence of hair follicle-inducing cells. Here we describe the method that we have used to isolate and cultivate epidermal stem cells.

Isolation and Cultivation of Skin-Derived Precursors.

Skin-derived precursors (SKPs) have been shown recently to be capable of inducing hair genesis and hair follicle regeneration. Here, we describe a protocol for SKP isolation and culture based on our experience and previous publications.

Design, synthesis, biological evaluation, homology modeling and docking studies of (E)-3-(benzo[d][1,3]dioxol-5-ylmethylene) pyrrolidin-2-one derivatives as potent anticonvulsant agents.

A series of (E)-3-(benzo[d][1,3]dioxol-5-ylmethylene)pyrrolidin-2-one derivatives were designed, synthesized, and evaluated for their anticonvulsant activities. In the preliminary screening, compounds 5, 6a-6f and 6h-6i showed promising anticonvulsant activities in MES model, while 6f and 6g represented protection against seizures at doses of 100 mg/kg and 0.5 h in scPTZ model. The most active compound 6d had a high-degree protection against the MES-induced seizures with ED50 value of 4.3 mg/kg and TD50 value of 160.9 mg/kg after intraperitoneal (i.p.) injection in mice, which provided 6d in a high protective index (TD50/ED50) of 37.4 comparable to the reference drugs. Beyond that, 6d has been selected and evaluated in vitro experiment to estimate the activation impact. Apparently, 6d clearly inhibits the Nav1.1 channel. Our preliminary results provide new insights for the development of small-molecule activators targeting specifically Nav1.1 channels to design potential drugs for treating epilepsy. The computational parameters, such as homology modeling, docking study, and ADME prediction, were made to exploit the results.

Mixed nitrifying bacteria culture under different temperature dropping strategies: Nitrification performance, activity, and community.

In this study, the nitrification performance, metabolic activity, antioxidant enzyme activity as well as bacterial community of mixed nitrifying bacteria culture under different temperature dropping strategies [(#1) growth temperature kept at 20 °C; (#2) sharp1 decreased from 20 °C to 10 °C; (#3) growth at 20 °C for 6 days followed by sharp decrease to 10 °C; and (#4) gradual decreased from 20 °C to 10 °C] were evaluated. It was shown that acclimation at 20 °C for 6 days allowed to maintain better nitrification activity at 10 °C. The nitrite oxidation capacity of nitrifiers was significantly correlated with the relative light unit (RLU) (p < .05) and the fluctuation of superoxide dismutase (SOD) enzyme activity (p < .01). With serial #3 showed the highest RLU levels and the least SOD enzyme fluctuation as compared to serials #2 and #4. Throughout the experimental period, Nitrosospira and Nitrosomonas as well as Nitrospira were identified as the predominant ammonia-oxidizing bacteria (AOB) and nitrate-oxidizing bacteria (NOB). The dynamic change of AOB/NOB ratios and nitrification activity in serials #2-#4 demonstrated that AOB recovered better than NOB with long-term 10 °C exposure, and the nitrification performance was mainly limited by the nitrite oxidation capacity of NOB. Applying 6 days acclimation at 20 °C was beneficial for the mixed nitrifying bacteria culture to cope with low temperature (10 °C) stress, possibly due to the maintenance of metabolic activity, antioxidant enzyme activity stability as well as appropriate AOB/NOB ratio.

Synthesis and Evaluation of 5-(o-Tolyl)-1H-tetrazole Derivatives as Potent Anticonvulsant Agents.

A series of 5-(o-tolyl)-1H-tetrazole derivatives were synthesized and evaluated for their anticonvulsant activities. 1-(2-Methylbenzyl)-5-(o-tolyl)-1H-tetrazole (3h) showed important anticonvulsant activity against the MES-induced seizures, as well as lower neurotoxicity with an ED50 value of 12.7 mg/kg and a TD50 value of over 500 mg/kg after intraperitoneal injection into mice, providing 3h with a high protective index (TD50 /ED50 ) of over 39.4. The achieved results prove that the distinctive compounds could be valuable as a model for future development, adaptation, and investigation to construct more active analogues.

A review: Driving factors and regulation strategies of microbial community structure and dynamics in wastewater treatment systems.

The performance and stabilization of biological wastewater treatment systems 1are closely related to the microbial community structure and dynamics. In this paper, the effects and mechanisms of influent composition, process configuration, operating parameters (dissolved oxygen [DO], pH, hydraulic retention time [HRT] and sludge retention time [SRT]) and environmental condition (temperature) to the change of microbial community structure and process performance (nitrification, denitrification, biological phosphorus removal, organics mineralization and utilization, etc.) are critically reviewed. Furthermore, some strategies for microbial community structure regulation, mainly bioaugmentation, process adjustment and operating parameters optimization, applied in the current wastewater treatment systems are also discussed. Although the recent studies have strengthened our understanding on the relationship between microbial community structure and wastewater treatment process performance, how to fully tap the microbial information, optimize the microbial community structure and maintain the process performance in wastewater treatment systems are still full of challenges.

Design and Synthesis of 5-Substituted Benzo[d][1,3]dioxole Derivatives as Potent Anticonvulsant Agents.

A series of 5-substituted benzo[d][1,3]dioxole derivatives was designed, synthesized, and tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. Neurotoxicity was determined by rotarod test. In the preliminary screening, six compounds, 3a, 3c, 3d, and 4d-f, showed promising anticonvulsant activities in the MES model, and compounds 4c and 4d exhibited full protection against seizures at doses of 300 mg/kg in the scPTZ model. Among the synthesized compounds, 3c as the most active compound showed high protection against the MES-induced seizures with an ED50 value of 9.8 mg/kg and a TD50 value of 229.4 mg/kg after intraperitoneal injection into mice, thus providing compound 3c with a high protective index (TD50 /ED50 ) of 23.4 comparable to those of reference antiepileptic drugs.

Angiotensin-converting enzyme insertion/deletion polymorphism and risk of myocardial infarction in an updated meta-analysis based on 34993 participants.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism and risk of myocardial infarction (MI) has been extensively studied. However, the results were in controversy. This study aimed to explore the association between ACE I/D polymorphism and risk of MI by using a meta-analysis. We retrieved the following databases to indentify eligible studies: Medline, Embase, ISI, VIP, CBM and Wan Fang database. The latest update was 10th May, 2012. Odds ratio and 95% confidence interval (95% CI) were used to present the strength of the association. A total of 40 case-control studies with 34993 participants were included. Overall, D allele of ACE I/D polymorphism was significantly associated with an increased risk of MI in genetic comparison models (OR (95% CI): 1.41 (1.22-1.64) for DD vs. II; 1.11 (1.01-1.21) for ID vs. II; 1.23 (1.10-1.37) for D carriers vs. II; 1.28 (1.15-1.43) for DD vs. I carriers and 1.06 (1.02-1.10) for D carriers vs. I carriers). Subgroup analyses, according to ethnicities and countries of participants also indicated that D allele was significantly associated with an increased risk of MI in Asians (especially for Chinese) and Caucasians (especially for English, French, Germans and Italians) (OR (95% CI) of DD vs. ID+II: 2.11 (1.65-2.70) for Asians and 1.15 (1.05-1.27) for Caucasians). In conclusion, this meta-analysis indicated that D allele of ACE I/D polymorphism was a possible risk factor for MI incidence for both Asians and Caucasians.