LDLR c.415G > A causes familial hypercholesterolemia by weakening LDLR binding to LDL.

BACKGROUND: Familial hypercholesterolemia (FH) is a prevalent hereditary disease that can cause aberrant cholesterol metabolism. In this study, we confirmed that c.415G > A in low-density lipoprotein receptor (LDLR), an FH-related gene, is a pathogenic variant in FH by in silico analysis and functional experiments. METHODS: The proband and his family were evaluated using the diagnostic criteria of the Dutch Lipid Clinic Network. Whole-exome and Sanger sequencing were used to explore and validate FH-related variants. In silico analyses were used to evaluate the pathogenicity of the candidate variant and its impact on protein stability. Molecular and biochemical methods were performed to examine the effects of the LDLR c.415G > A variant in vitro. RESULTS: Four of six participants had a diagnosis of FH. It was estimated that the LDLR c.415G > A variant in this family was likely pathogenic. Western blotting and qPCR suggested that LDLR c.415G > A does not affect protein expression. Functional studies showed that this variant may lead to dyslipidemia by impairing the binding and absorption of LDLR to low-density lipoprotein ( LDL). CONCLUSION: LDLR c.415G > A is a pathogenic variant in FH; it causes a significant reduction in LDLR's capacity to bind LDL, resulting in impaired LDL uptake. These findings expand the spectrum of variants associated with FH.

FGF23 alleviates neuronal apoptosis and inflammation, and promotes locomotion recovery via activation of PI3K/AKT signalling in spinal cord injury.

Fibroblast growth factor 23 (FGF23) regulates neuronal morphology, synaptic growth and inflammation; however, its involvement in spinal cord injury (SCI) remains unclear. Therefore, the present study aimed to investigate the effect of FGF23 on neuronal apoptosis, inflammation and locomotion recovery, as well as its underlying mechanism in experimental SCI models. Primary rat neurons were stimulated with H2O2 to establish an in vitro model of SCI and were then transfected with an FGF23 overexpression (oeFGF23) or short hairpin RNA (shFGF23) adenovirus-associated virus and treated with or without LY294002 (a PI3K/AKT inhibitor). Subsequently, an SCI rat model was constructed, followed by treatment with oeFGF23, LY294002 or a combination of the two. FGF23 overexpression (oeFGF23 vs. oeNC) decreased the cell apoptotic rate and cleaved-caspase3 expression, but increased Bcl-2 expression in H2O2-stimulated neurons, whereas shFGF23 transfection (shFGF23 vs. shNC) exhibited the opposite effect (all P<0.05). Furthermore, FGF23 overexpression (oeFGF23 vs. oeNC) could activate the PI3K/AKT signalling pathway, whereas treatment with the PI3K/AKT inhibitor (LY294002) (oeFGF23 + LY294002 vs. LY294002) attenuated these effects in H2O2-stimulated neurons (all P<0.05). In SCI model rats, FGF23 overexpression (oeFGF23 vs. oeNC) reduced the laceration and inflammatory cell infiltration in injured tissue, decreased TNF-α and IL-1ß levels, and improved locomotion recovery (all P<0.05); these effects were attenuated by additional administration of LY294002 (oeFGF23 + LY294002 vs. LY294002) (all P<0.05). In conclusion, FGF23 alleviated neuronal apoptosis and inflammation, and promoted locomotion recovery via activation of the PI3K/AKT signalling pathway in SCI, indicating its potential as a treatment option for SCI; however, further studies are warranted for validation.

In vitro assessment of the pathogenicity of the LDLR c.2160delC variant in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an inherited disorder with markedly elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. Although many mutations have been reported in FH, only a few have been identified as pathogenic mutations. This study aimed to confirm the pathogenicity of the LDL receptor (LDLR) c.2160delC variant in FH. METHODS: In this study, the proband and her family members were systematically investigated, and a pedigree map was drawn. High-throughput whole-exome sequencing was used to explore the variants in this family. Next, quantitative polymerase chain reaction (qPCR), western blot (WB) assays, and flow cytometry were conducted to detect the effect of the LDLR c.2160delC variant on its expression. The LDL uptake capacity and cell localization of LDLR variants were analyzed by confocal microscopy. RESULTS: According to Dutch Lipid Clinic Network (DLCN) diagnostic criteria, three FH patients were identified with the LDLR c.2160delC variant in this family. An in-silico analysis suggested that the deletion mutation at the 2160 site of LDLR causes a termination mutation. The results of qPCR and WB verified that the LDLR c.2160delC variant led to early termination of LDLR gene transcription. Furthermore, the LDLR c.2160delC variant caused LDLR to accumulate in the endoplasmic reticulum, preventing it from reaching the cell surface and internalizing LDL. CONCLUSIONS: The LDLR c.2160delC variant is a terminating mutation that plays a pathogenic role in FH.

In Situ Study of Twin Boundary Stability in Nanotwinned Copper Pillars under Different Strain Rates.

The nanoscopic deformation of ⟨111⟩ nanotwinned copper nanopillars under strain rates between 10-5/s and 5 × 10-4/s was studied by using in situ transmission electron microscopy. The correlation among dislocation activity, twin boundary instability due to incoherent twin boundary migration and corresponding mechanical responses was investigated. Dislocations piled up in the nanotwinned copper, giving rise to significant hardening at relatively high strain rates of 3-5 × 10-4/s. Lower strain rates resulted in detwinning and reduced hardening, while corresponding deformation mechanisms are proposed based on experimental results. At low/ultralow strain rates below 6 × 10-5/s, dislocation activity almost ceased operating, but the migration of twin boundaries via the 1/4 ⟨101¯ ⟩ kink-like motion of atoms is suggested as the detwinning mechanism. At medium strain rates of 1-2 × 10-4/s, detwinning was decelerated likely due to the interfered kink-like motion of atoms by activated partial dislocations, while dislocation climb may alternatively dominate detwinning. These results indicate that, even for the same nanoscale twin boundary spacing, different nanomechanical deformation mechanisms can operate at different strain rates.

The promising novel therapies for familial hypercholesterolemia.

BACKGROUND: The incidence of premature atherosclerotic cardiovascular disease in familial hypercholesterolemia (FH) is high. In recent years, novel therapeutic modalities have shown significant lipid-lowering ability. In this paper, we summarize the recent developments in novel therapies for FH via the treatment of different targets and discuss the characteristics of each targeted therapy. Based on the process of protein synthesis, we attempt to summarize the direct-effect targets including protein, RNA, and DNA. METHODS: For this systematic review, relevant studies are assessed by searching in several databases including PubMed, Web of Science, Scopus, and Google Scholar. The publications of original researches are considered for screening. RESULTS: Most drugs are protein-targeted such as molecule-based and monoclonal antibodies, including statins, ezetimibe, alirocumab, evolocumab, and evinacumab. Both antisense oligonucleotide (ASO) and small interfering RNA (siRNA) approaches, such as mipomersen, vupanorsen, inclisiran, and ARO-ANG3, are designed to reduce the number of mRNA transcripts and then degrade proteins. DNA-targeted therapies such as adeno-associated virus or CRISPR-Cas9 modification could be used to deliver or edit genes to address a genetic deficiency and improve the related phenotype. CONCLUSION: While the therapies based on different targets including protein, RNA, and DNA are on different stages of development, the mechanisms of these novel therapies may provide new ideas for precision medicine.

Research progress of the correlation between genotype and phenotype in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease characterized by left ventricular hypertrophy with prevalence of 1/500-1/200. Up to now, 1500 mutations in more than 30 genes have been found to be related to the disease. Pathogenic gene mutations together with polymorphisms of modifying genes and environmental factors play various roles in the disease processes, resulting in phenotypic heterogeneity of the disease, ranging from no symptoms to sudden cardiac death. The pathological phenotypes of HCM mainly include cardiomyocyte hypertrophy, disordered array, fibrosis, myocardial ischemia, and others. In recent years, many research efforts have been devoted to exploring the influence of HCM genotype on phenotype, and development of treatment methods based on genetics. This article focuses on the correction between HCM genotype and phenotype and summarizes the research progresses on HCM in terms of pathogenic genes, pathogenesis, associated modification factors and treatment methods, thereby providing insights on the future research and development on the genetics of HCM.

Cervical Alignment of Patients with Basilar Invagination: A Radiological Study.

OBJECTIVE: To investigate the cervical alignment and the relative range of motion (ROM) in patients with basilar invagination (BI). METHODS: A total of 40 BI cases (38.1 years old ± 17.9 years old, 19 male and 21 female) and 80 asymptomatic individuals (33.8 years old ± 10.8 years old, 40 male and 40 female) were included. The Skull-C2 /Skull-BV, Skull-C7 , C2 -C7 /BV-C7 wall angles, C0 -C2 /C0 -BV, C0 -C7 , C1 -C7 , and C2 -C7 /BV-C7 angles were measured in dynamic X-ray images (including neutral, extension, and flexion positions). Correlation between the upper and lower cervical curvatures were analyzed. The total, extension, and flexion ROMs of these angles were calculated, respectively. RESULTS: The BI patients had a smaller C0 -C2 /C0 -BV angle (18.2° ± 16.4° vs 30.9° ± 9.3°), but larger C2 -C7 /BV-C7 (32.2° ± 16.1° vs 19.4° ± 10.6°) and C2 -C7 /BV-C7 wall angles (37.8° ± 17.2° vs 23.6° ± 10.2°) than the control group in neutral position. The upper and lower curvatures correlated negatively in neutral (r = -0.371), extension (r = -0.429), and flexion (r = -0.648) positions among BI patients, as well as in extension position (r = -0.317) among control group. The BI patients presented smaller total ROMs in Skull-C2 /Skull-BV (12.3° ± 16.6° vs 19.7° ± 10.9°), C0 -C2 /C0 -BV (8.1° ± 11.1° vs 17.6° ± 10.5°), and C0 -C7 angles (57.8° ± 14.2° vs 78.3° ± 17.9°), but a larger total ROM in C2 -C7 /BV-C7 wall angle (52.8° ± 13.9° vs 27.0° ± 16.1°) than the control group. The BI patients also presented smaller extension ROMs in Skull-C2 /Skull-BV (6.9° ± 9.4° vs 12.5° ± 9.3°), Skull-C7 (24.5° ± 10.9° vs 30.7° ± 12.5°), and C0 -C2 /C0 -BV angles (4.4° ± 7.8° vs 9.9° ± 8.6°) than the control group. Moreover, the BI patients showed smaller absolute values of flexion ROMs in Skull-C2 /Skull-BV (-5.2° ± 9.4° vs -7.3° ± 8.0°), C0 -C2 /C0 -BV (-3.2° ± 8.8° vs -7.7° ± 8.7°), and C0 -C7 angles (-33.2° ± 13.0° vs -52.8° ± 19.2°), but a larger absolute value of flexion ROM in C2 -C7 /BV-C7 wall angle (-33.9° ± 14.8° vs -8.2° ± 15.1°). CONCLUSION: The cervical spine was stiffer in BI patients than the asymptomatic individuals, especially in the upper cervical curvature. The negative correlation between upper and lower cervical curvatures was more obvious in BI patients.

Two Novel Disease-Causing Mutations in the LDLR of Familial Hypercholesterolemia.

As an autosomal dominant disorder, familial hypercholesterolemia (FH) is mainly caused by pathogenic mutations in lipid metabolism-related genes. The aim of this study is to investigate the genetic mutations in FH patients and verify their pathogenicity. First of all, a pedigree investigation was conducted in one family diagnosed with FH using the Dutch Lipid Clinic Network criteria. The high-throughput sequencing was performed on three family members to explore genetic mutations. The effects of low-density lipoprotein receptor (LDLR) variants on their expression levels and activity were further validated by silico analysis and functional studies. The results revealed that LDLC levels of the proband and his daughter were abnormally elevated. The whole-exome sequencing and Sanger sequencing were used to confirm that there were two LDLR missense mutations (LDLR c.226 G > C, c.1003 G > T) in this family. Bioinformatic analysis (Mutationtaster) indicated that these two mutations might be disease-causing variants. In vitro experiments suggested that LDLR c.226 G > C and c.1003 G > T could attenuate the uptake of Dil-LDL by LDLR. In conclusion, the LDLR c.226 G > C and c.1003 G > T variants might be pathogenic for FH by causing uptake dysfunction of the LDLR.

The LDLR c.501C>A is a disease-causing variant in familial hypercholesterolemia.

BACKGROUND: As an autosomal dominant disorder, familial hypercholesterolemia (FH) is mainly attributed to disease-causing variants in the low-density lipoprotein receptor (LDLR) gene. The aim of this study was to explore the molecular mechanism of LDLR c.501C>A variant in FH and assess the efficacy of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor treatment for FH patients. METHODS: The whole-exome sequencing was performed on two families to identify disease-causing variants, which were verified by Sanger sequencing. The function of LDLR variant was further explored in HEK293 cells by Western Blot and confocal microscopy. Besides, the therapeutic effects of PCSK9 inhibitor treatment for two probands were assessed for 3 months. RESULTS: All members of the two families with the LDLR c.501C>A variant showed high levels of LDLC. The relationship between the clinical phenotype and LDLR variants was confirmed in the current study. Both in silico and in vitro analyses showed that LDLR c.501C>A variant decreased LDLR expression and LDL uptake. PCSK9 inhibitor treatment lowered the lipid level in proband 1 by 24.91%. However, the treatment was ineffective for proband 2. A follow-up study revealed that the PCSK9 inhibitor treatment had low ability of lipid-lowering effect in the patients. CONCLUSIONS: LDLR c.501C>A variant might be pathogenic for FH. The PCSK9 inhibitor therapy is not a highly effective option for treatment of FH patients with LDLR c.501C>A variant.

Morphological Evaluation of the Subaxial Cervical Spine in Patients with Basilar Invagination: A CT-based Study.

STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate the morphologic features of the subaixal cervical spine in patients with basilar invagination (BI) and provide information for the accurate screw placement in this region. SUMMARY OF BACKGROUND DATA: BI is a congenital anomaly, comprising a wide range of abnormal structures. The screw fixation can be required in situation that BI is combined with subaxial cervical spine pathologies. However, there are no literatures specifically addressed the subaxial cervical morphology of BI. METHOD: A total of 42 BI patients were included in this retrospective study. Forty-two patients without head or cervical disease were matched for sexes and ages. Information on radiographic features of the subaxial cervical spine was collected and compared systematically. RESULTS: There were no differences in the age and sex between the BI and control group. The BI group manifested a wider pedicle and laminar than the control group at all cervical levels, except for the pedicle of C6 and C7, and the laminar of C3 and C6. In addition, the BI group had a wider lateral mass from C3 to C5 than the control group. There were no differences in most measurements of the length of pedicle, laminar, and lateral mass. CONCLUSION: BI patients have a wider pedicle and laminar than the general population in the subaxial cervical spine, but the same size in length of pedicle, laminar, and lateral mass.Level of Evidence: 4.

The expression profile of platelet-derived miRNA in coronary artery disease patients with clopidogrel resistance.

Clopidogrel is widely used for antiplatelet therapy in patients with coronary artery disease (CAD), but clopidogrel resistance (CR) is relatively common in these patients. The goal of our study was to explore the platelet-derived miRNA expression profile of CR in CAD patients. In this study, 66 CAD patients treated with dual antiplatelet therapy (clopidogrel 75 mg once daily plus aspirin 100 mg once daily) were included. According to inhibition of platelet aggregation (IPA), we divided these patients into CR group (IPA <30%) and control group (IPA ≥30%). The concentrations of clopidogrel and clopidogrel active metabolites in plasma were obtained using UHPLC-Q-Orbitrap HRMS method. The platelet-derived miRNA expression profiles of these subjects were detected by high-throughput sequencing and qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for function prediction of differentially expressed miRNAs. Our results suggested no significant difference of clopidogrel and active metabolic derivative concentrations between CR group and control group. Correlation analysis showed no significant association between clopidogrel concentration and IPA; active metabolic derivative and IPA. In addition, 67 platelet-derived miRNAs were differentially expressed between three CR and three control patients. After adjusting, eight miRNAs might be related to CR in CAD. In our validation cohort (30 CR patients and 30 control group), miRNA-142-3p and miRNA-24-3p expression levels were significantly upregulated, and miRNA-411-3p expression was significantly downregulated in the CR group. In conclusion, the miRNA-142-3p, miRNA-24-3p, and miRNA-411-3p might be potential markers for CR in CAD patients.

Corrigendum: Ideal Cardiovascular Health Metrics and Incidence of Ischemic Stroke Among Hypertensive Patients: A Prospective Cohort Study.

[This corrects the article DOI: 10.3389/fcvm.2020.590809.].

Ideal Cardiovascular Health Metrics and Incidence of Ischemic Stroke Among Hypertensive Patients: A Prospective Cohort Study.

Background: This study aimed to assess the relationship between ideal cardiovascular health (CVH) metrics and incident ischemic stroke (IS) in hypertensive patients, especially those with hyperhomocysteinemia (HHcy). Methods: A prospective cohort study enrolled 5,488 hypertensive patients in Nanshan District of Shenzhen City in southern China from September 2011 to December 2017. CVH metrics were defined according to the American Heart Association. Cox proportional hazards models were used to examine the associations between the number of ideal CVH metrics and the incidence of IS by calculating multivariable-adjusted hazard ratios (HRs) and 95% CI. Results: During an average follow-up of 5.7 years, 340 IS patients were identified. Compared with those having 0 ideal CVH metrics, the HRs (95% CIs) for IS among those with 1, 2, 3, 4, and 5-6 ideal CVH metrics were 0.62 (0.31-1.25), 0.37 (0.19-0.74), 0.37 (0.18-0.74), 0.34 (0.16-0.71), and 0.28 (0.12-0.63), respectively (P < 0.001). An ideal healthy diet score and ideal fasting blood glucose level were independently associated with IS among participants, with HRs (95% CIs) of 0.53 (0.33-0.86) and 0.32 (0.17-0.66), respectively. Additionally, compared with those with normal total homocysteine (tHcy) levels (<15 µmol/L), the HR (95% CI) for IS among participants with HHcy and who had 5-6 ideal CVH metrics was 0.50 (0.27-0.92). Conclusion: An increased number of ideal CVH metrics was inversely associated with the incidence of IS in hypertensive patients. The participants with HHcy who had 5-6 ideal CVH metrics exhibited a lower IS risk than those with normal tHcy levels.

Calcified Aortic Valve Disease in Patients With Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is a rare autosomal gene deficiency disease with increased low-density lipoprotein cholesterol, xanthoma, and premature coronary heart disease. Calcified aortic valve disease (CAVD) is prevalent in FH patients, resulting in adverse events and heavy health care burden. Aortic valve calcification is currently considered an active biological process, which shares several common risk factors with atherosclerosis, including aging, hypertension, dyslipidemia, and so on. Unfortunately, the pathogenesis and therapy of CAVD in FH are still controversial. There is no pharmacological intervention recommended to delay the development of CAVD in FH, and the only effective treatment for severe CAVD is aortic valve replacement. In this review, we summarize the detailed description of the pathophysiology, molecular mechanism, risk factors, and treatment of CAVD in FH patients.

[The role of DNA hydroxymethylation in the regulation of atherosclerosis].

As an epigenetic modification, DNA hydroxymethylation plays a significant role in regulating gene expression. In recent years, there has been increasing evidence that suggests abnormal changes of 5-hydroxymethylcytosine (5hmC) and ten-eleven translocation (TET) family proteins in cardiovascular diseases, indicating cardiovascular diseases are closely connected with DNA hydroxymethylation. The level of DNA hydroxymethylation is affected by some common risk factors of atherosclerosis, such as aging, gender, hypertension and smoking. It is also related to the immune and inflammatory reaction involved in the process of atherosclerosis as well as the function of endothelial cells and vascular smooth muscle cells. In this review, we summarize the mechanism and research status of DNA hydroxymethylation and TET family proteins towards atherosclerosis, aiming to provide a reference for the development, diagnosis and treatment of atherosclerosis.

The Role of Transcription Factor 21 in Epicardial Cell Differentiation and the Development of Coronary Heart Disease.

Transcription factor 21 (TCF21) is specific for mesoderm and is expressed in the embryos' mesenchymal derived tissues, such as the epicardium. It plays a vital role in regulating cell differentiation and cell fate specificity through epithelial-mesenchymal transformation during cardiac development. For instance, TCF21 could promote cardiac fibroblast development and inhibit vascular smooth muscle cells (VSMCs) differentiation of epicardial cells. Recent large-scale genome-wide association studies have identified a mass of loci associated with coronary heart disease (CHD). There is mounting evidence that TCF21 polymorphism might confer genetic susceptibility to CHD. However, the molecular mechanisms of TCF21 in heart development and CHD remain fundamentally problematic. In this review, we are committed to providing a detailed introduction of the biological roles of TCF21 in epicardial fate determination and the development of CHD.

Electrochemical Assessment of Anticancer Compounds on the Human Tongue Squamous Carcinoma Cells.

The most common oral cancer is squamous cell carcinoma (SCC) and its highest occurrence is in the tongue. Almost 30% of patients with one primary head and neck tumor will have a second primary malignancy. In recent studies, two novel plant extracts, andrographolide and cannabidiol (CBD), have been exploited for their anticancer effects. Here, we investigated the cytotoxic effects of these two compounds on SCC-25 cells, a human tongue squamous carcinoma cell line, and compared the outcomes with two chemotherapeutic drugs, cisplatin and fluorouracil. Electric cell substrate impedance sensing (ECIS) system was applied to measure frequency- and time-dependent impedance of SCC-25 cell-covered electrodes and to further assess subtle changes in cell morphology and micromotion in response to different concentrations (0, 10, 30, 100, and 300 µM) of these compounds. AlamarBlue and Annexin V/7-AAD binding assays were used to measure the concentration dependent changes in viability and apoptosis of SCC-25 cells. Our results demonstrate that 24 hours after exposure to 30 µM CBD can significantly decrease the micromotion rate, damage the integrity of cell morphology, reduce cell viability, and induce higher apoptosis in treated SCC-25 cells, while the other three drugs attain similar effects at the concentration of 100 µM or higher. The apoptosis-induced changes in cell morphology and micromotion monitored by ECIS correlate well with biochemical assays. Thus, both frequency- and time-dependent impedance measurements using ECIS can be used to real-time follow cancer cell activities in response to anticancer drugs with different temporal cytotoxicity profiles.

Association between hypertensive pregnancy disorders and future risk of stroke in Taiwan: a Nationwide population-based retrospective case-control study.

BACKGROUND: The incidence of female stroke has increased gradually and has begun occurring at a younger age in recent years. Given that women live longer than men, stroke would cause more negative and longer-term impacts on the rest of the lives of women. There are few related studies on Asian women. We aimed to evaluate stroke risk in Asian women following hypertensive pregnancy disorders. METHODS: Using the Taiwan National Health Insurance database, we designed a retrospective study that included pregnant women between 2000 and 2013. We selected an age-matched control group of women without hypertensive pregnancy disorders at a 1:3 ratio. The endpoint was any episode of stroke; otherwise, the patients were tracked until December 31, 2013. After the index date until the end of 2013, Cox proportional hazards analysis was used to compare the risk of incident stroke. The risk factors for stroke were determined using Cox proportional regression to calculate the hazard ratio (HR) compared with the control group. RESULTS: During the follow-up period, the Kaplan-Meier analysis indicated that patients with hypertensive pregnancy disorders had a significantly higher risk of developing stroke than did patients without hypertensive pregnancy disorders (log-rank test P < 0.001). Multivariate Cox regression analysis demonstrated that the case group had a 2.134-fold increased risk of stroke (HR = 2.134; 95% CI = 1.817-2.505; P < 0.001). CONCLUSION: Our study provided evidence of an increased risk of stroke in patients with hypertensive pregnancy disorders. Compared with those without such disorders, the patients who had experienced the disorders had a 2.134-fold (P < 0.001) higher risk of developing stroke in the future.

The alterations of mitochondrial DNA in coronary heart disease.

Coronary heart disease (CHD) is the major cause of death in modern society. CHD is characterized by atherosclerosis, which could lead to vascular cavity stenosis or obstruction, resulting in ischemic cardiac conditions such as angina and myocardial infarction. In terms of the mitochondrion, the main function is to produce adenosine triphosphate (ATP) for cells. And the alterations (including mutations, altered copy number and haplogroups) of mitochondrial DNA (mtDNA) are associated with the abnormal expression of oxidative phosphorylation (OXPHOS) system, resulting in mitochondrial dysfunction, then leading to perturbation on the electron transport chain and increased ROS generation and reduction in ATP level, contributing to ATP-producing disorders and oxidative stress, which may further accelerate development or vulnerability of atherosclerosis and myocardial ischemic injury. Therefore, the mtDNA defects may play an important role in making an early diagnosis, identifying disease-specific biomarkers and therapeutic targets, and predicting outcomes for patients with atherosclerosis and CHD. In this review, we aim to summarize the contribution of mtDNA mutations, altered mtDNA copy number and mtDNA haplogroups on the occurrence and development of CHD.

Anatomical analysis of the occipital bone in patients with basilar invagination: a computed tomography-based study.

BACKGROUND CONTEXT: The occipital bone is often involved in the surgical treatment of basilar invagination (BI). However, the anatomy of the occipital bone associated with BI patients has yet to be investigated. PURPOSE: To present a morphological map of the occipital bone in BI patients and help guide screw placement for occipitocervical fusion. STUDY DESIGN: A retrospective case-control study. METHODS: Radiological measurements of the occipital bone were performed on computed tomography images based on a matrix of 99 points centered around the external occipital protuberance (EOP) in a cohort of 50 BI patients and 50 cases with no head and cervical disease. The comparison between the BI group and the control group was assessed using Student t analysis and p<.05 was considered statistically significant. RESULTS: All thicknesses measured from points of the matrix in the BI group were thinner than those in the control group (p<.05). The maximum thicknesses in both groups were located at the center of the EOP, which were 15.11±2.84 mm in the BI group and 17.56±3.03 mm in the control group, respectively. Additionally, thickness decreased with the distance away from the center of EOP. CONCLUSIONS: The occipital bone in BI patients is thinner than that in the general population. A limited safe zone in BI patients is available for surgeons to place screws, which may need to be fully evaluated before operation.