Lipoprotein (a)-Related Inflammatory Imbalance: A Novel Horizon for the Development of Atherosclerosis.

PURPOSE OF REVIEW: The primary objective of this review is to explore the pathophysiological roles and clinical implications of lipoprotein(a) [Lp(a)] in the context of atherosclerotic cardiovascular disease (ASCVD). We seek to understand how Lp(a) contributes to inflammation and arteriosclerosis, aiming to provide new insights into the mechanisms of ASCVD progression. RECENT FINDINGS: Recent research highlights Lp(a) as an independent risk factor for ASCVD. Studies show that Lp(a) not only promotes the inflammatory processes but also interacts with various cellular components, leading to endothelial dysfunction and smooth muscle cell proliferation. The dual role of Lp(a) in both instigating and, under certain conditions, mitigating inflammation is particularly noteworthy. This review finds that Lp(a) plays a complex role in the development of ASCVD through its involvement in inflammatory pathways. The interplay between Lp(a) levels and inflammatory responses highlights its potential as a target for therapeutic intervention. These insights could pave the way for novel approaches in managing and preventing ASCVD, urging further investigation into Lp(a) as a therapeutic target.

Application of hyperbaric oxygen therapy in diabetic foot ulcers: A meta-analysis.

Hyperbaric oxygen therapy (HBOT) has been used in patients with diabetic foot ulcers (DFU) for many years, but its clinical efficacy is still controversial. Therefore, this study explored the efficacy of HBOT applied to DFU by means of meta-analysis. PubMed, Cochrane Library, Embase, CNKI and Wanfang databases were searched, from database inception to October 2023, and published randomised controlled trials (RCTs) of HBOT in DFU were collected. Two investigators independently screened the collected literature, extracted relevant data and assessed the quality of the literature. Review Manager 5.4 software was applied for data analysis. Twenty-nine RCTs with 1764 patients were included. According to the combined results, when compared with conventional treatment, HBOT significantly increased the complete healing rate of DFUs (46.76% vs. 24.46%, odds ratio [OR]: 2.83, 95% CI: 2.29-3.51, p < 0.00001) and decreased the amputation rate (26.03% vs. 45.00%, OR: 0.41, 95% CI: 0.18-0.95, p = 0.04), but the incidence of adverse events was significantly higher in patients (17.37% vs. 8.27%, OR: 2.49, 95% CI: 1.35-4.57, p = 0.003), whereas there was no significant difference in the mortality (6.96% vs. 12.71%, OR: 0.52, 95% CI: 0.21-1.28, p = 0.16). Our results suggest that HBOT is effective in increasing the complete healing rate and decreasing the amputation rate in patients with DFUs, but increases the incidence of adverse events, while it has no significant effect on mortality.

Establishment of an intelligent cervical vertebrae maturity assessment system based on cone beam CT data.

To establish an intelligent cervical vertebra maturity assessment system, and to evaluate the reliability and clinical value of the system. Sixty children aged were recruited in the study. Lateral cephalometric radiograph and cone beam CT (CBCT) were taken at the same period. Based on the CBCT data, the system automatically extracted the patient's facial area through Otsu's method, intercepted the sagittal plane by three-dimensional least squares method, captured the second to fourth cervical vertebrae by superpixel segmentation. And then selected points were marked automatically through morphological algorithm and manual method. Consistency test was performed on the two sets of data to compare the reliability of automated cervical morphology capture. According to the parameters of morphological identification, positioning and staging algorithms were designed to form the intelligent cervical vertebra maturity assessment system. The cervical vertebra maturity was also judged manually on the lateral cephalometric radiograph. The weighted Kappa test and the Gamma correlation coefficient were subsequently applied to evaluate the consistency and correlation. The results showed that the cervical vertebra features automatically captured based on CBCT data had a high accuracy on the overall morphological recognition. In the prediction of 8 inflection points out of 13 points, there was no significant difference between automatic and manual method on both X and Y axes (all >0.05). The assessment results of the cervical vertebra maturity of the intelligent system had strong consistency and correlation with the manual recognition results (weighted Kappa value=0.877, Gamma value=0.991, both <0.05). The intelligent cervical vertebrae maturity assessment system based on CBCT data established in this study presents reliable outcome and high degree of automation, indicating that the system may be used clinically.

CYP17A1 Polymorphisms Are Linked to the Risk of Coronary Heart Disease in a Case-Control Study.

BACKGROUND: Cytochrome P450 17A1 (CYP17A1) catalyzes the formation and metabolism of steroid hormones and is required for cortisol and androgens. There is increasing evidence that CYP17A1 plays an important role in the development of coronary heart disease (CHD). However, the association of CYP17A1 polymorphisms and CHD susceptibility is still not clear. METHODS: We conducted a case-control study with 396 CHD cases and 461 healthy controls from Hainan province, China. Using the Agena MassARRAY platform, we genotyped 4 genetic variants (rs3740397, rs1004467, rs4919687, and rs3781286) in CYP17A1. Logistic regression analysis was used to assess the association of CYP17A1 polymorphisms with CHD risk by odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: It showed that A allele of CYP17A1 rs4919687 carried with a 1.59-fold increased risk of CHD (OR = 1.59; 95% CI = 1.26-1.99; P < 0.001). Also, rs4919687 was significantly associated with CHD risk under various models (homozygote: OR = 3.60; 95% CI = 1.64-7.83; P = 0.001; dominant: OR = 1.51; 95% CI = 1.06-2.13; P = 0.021; recessive: OR = 3.28; 95% CI = 1.51-7.14; P = 0.003; additive: OR = 1.56; 95% CI = 1.17-2.07; P = 0.002). Moreover, analysis showed that Ars1004467 Ars4919687 haplotype was a protective factor of CHD (OR = 0.64; 95% CI = 0.48-0.86; P = 0.002). CONCLUSIONS: Our study suggests that CYP17A1 polymorphisms are associated with CHD susceptibility in the Hainan Han Chinese population.

[Mouse immune responses elicited by eukaryotic expression plasmid and prokaryotically expressed protein of Brugia malayi myosin 29 epitope].

Objective: To determine the immune responses elicited in BALB/c mice by vaccination with eukaryotic expression plasmid pcDNA3.1(+)-BmM29 containing Brugia malayi myosin 29(BmM29) epitode and prokaryotically expressed recombinant BmM2 protein(rBmM29) respectively. Methods: rBmM29 protein was expressed in E. coli strain BL21, purified as recombinant protein vaccine, and administered via multiple subcutaneous injections. The purified recombinant plasmid pcDNA3.1(+)-BmM29 was used as the nucleic acid vaccine and injected into the tibialis anterior muscle. Sixty BALB/c mice were randomized to receive three immunizations(with intervals of 2 weeks) with PBS (100 µg, group A), pcDNA3.1(+)/CpG (100 µg/30 µg, group B), pcDNA3.1(+)-BmM29/CpG (100 µg/30 µg, group C), rBmM29/CpG(50 µg/30 µg, group D), or pcDNA3.1(+)-BmM29/rBmM29/CpG (two injections of pcDNA3.1(+)-BmM29/CpG 100 µg/30 µg followed by a rBmM29/CpG 50 µg/30 µg). Serum was prepared through ophthalmectomy at week 4, 6, and 8 after primary immunization, and the serum IgG titer was determined by ELISA. The mice were sacrificed at week 8, splenocyte suspension cultured for 48 h, and levels of INF-γ and IL-4 in the supernatant detected by ELISA. Results: ELISA results showed that the A490 values of serum IgG in groups A-E were 0.038 ± 0.050,0.053 ± 0.009,0.360 ± 0.035,0.456 ± 0.025,0.370 ± 0.025 at week 4,0.045 ± 0.003,0.045 ± 0.005,0.510 ± 0.018,0.548 ± 0.010,0.552 ± 0.018 at week 6, and 0.041 ± 0.004,0.044 ± 0.009,0.606 ± 0.047,0.674 ± 0.042,0.770 ± 0.041 at week 8, significantly higher in groups C, D and E than in groups A and B (P < 0.05) at all time points, and significantly higher in group E than in groups C and D(P < 0.05) at week 8. The IFN-γ levels in splenocyte culture supernatant at week 8 after primary immunization were (47.72 ± 8.94),(50.43 ± 2.81),(304.78 ± 8.42),(242.28 ± 5.99), and(426.52 ± 6.76) pg/ml in groups A-E, respectively, significantly higher in groups C-D than in groups A and B(P < 0.05), and in group E than in groups C and D(P < 0.05). The IL-4 levels in splenocyte culture supernatant were(60.00 ± 11.14),(57.71 ± 15.95),(93.17 ± 12.56),(96.67 ± 11.48), and (101.17 ± 5.81) pg/ml, significantly higher in groups C-D than in groups A and B(P < 0.05). Conclusion: Both the recombinant plasmid pcDNA3.19(+)-BmM29 and rBmM29 protein could elicit specific humoral and cellular immune responses in mice. Combined immunization with nucleic acid vaccine and protein vaccine is superior to each of the two alone.

Combined Association of Serum Uric Acid and Metabolic Syndrome with Chronic Kidney Disease in Hypertensive Patients.

BACKGROUND/AIMS: Chronic kidney disease (CKD) is one of the major complications of hypertension. It is not only associated with the future burden of end-stage renal disease but also affects mortality and cardiovascular outcomes caused by hypertension. To help understand the pathogenesis and early prevention of progressive CKD, this large-scale study is designed to determine the complex association between serum uric acid (SUA), metabolic syndrome and the prevalence of CKD in hypertensive patients. METHODS: A total of 19,848 hypertensive subjects were enrolled in this cross-sectional study. Patients with proteinuria and/or an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 were considered CKD cases. RESULTS: Hypertensive subjects with CKD had a higher prevalence of hyperuricemia and metabolic syndrome, as well as higher levels of SUA, BMI, waist circumference (WC), SBP, DBP, TG, fasting blood glucose and lower levels of HDL-C. Compared to patients without CKD, the multivariate-adjusted odds ratios [ORs, 95% confidence interval (CI)] for CKD patients were 2.30 (2.02-2.63) for hyperuricemia, 1.21 (1.04-1.41) for abdominal obesity, 1.21 (1.06-1.38) for elevated TG, 1.29 (1.06-1.56) for low HDL-C, 1.54 (1.36-1.75) for elevated fasting glucose, and 1.49 (1.30-1.71) for metabolic syndrome. Increasing SUA levels and number of individual metabolic syndrome components were associated with an increased prevalence of CKD. Compared with patients classified in the lowest SUA categories and with ≤1 metabolic syndrome components, subjects with HUA and 4 metabolic syndrome components had a 5.77-fold increased OR for CKD based on the multivariate-adjusted analysis. CONCLUSION: Both elevated SUA and metabolic syndrome are associated with an increased prevalence of CKD in hypertensive subjects. Subjects with higher SUA and sum of individual metabolic syndrome components simultaneously have a higher prevalence of CKD.

CircSorbs1 regulates myocardial regeneration and reduces cancer therapy-related cardiovascular toxicity through the Mir-99/GATA4 pathway.

Due to the cancer therapy-related cardiovascular toxicity, heart failure following cancer therapy has a significant mortality rate. Gene-targeted therapy promotes the re-entry of existing cardiomyocytes into the cell cycle to achieve myocardial regeneration, which is a promising strategy for preventing and treating heart failure after myocardial infarction. Circular RNAs (circRNAs) are considered as potential targets for myocardial regeneration due to their strong stability, resistance to degradation, and potential role in heart development and cardiovascular diseases. By comparing the myocardial tissue of mice in the sham operation group and the Doxorubicin therapy group (DOX), we observed a significant decrease in Cirsorbs expression in the DOX group. Cirsorbs was predominantly localized in cardiomyocytes and exhibited high conservation. Subsequent investigations revealed that Cirsorbs could promote myocardial proliferation and inhibit myocardial apoptosis. Mechanistic studies further demonstrated that Cirsorbs could bind to miR99 and reduce its expression level. Meanwhile, miR99 was found to bind to GATA4 mRNA and decrease its expression level. The binding of Cirsorbs to miR99 alleviated the repression of miR99, thereby enhancing GATA4 expression and the transcription of downstream cyclin A2 and cyclin E1. This, in turn, increased cardiomyocyte proliferation and reduced apoptosis. In conclusion, Cirsorbs holds promise as an effective target for myocardial regeneration in reducing cancer therapy-related cardiovascular toxicity.

Novel polymorphisms in CYP4A22 associated with susceptibility to coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) has become a worldwide public health problem. Genetic factors are considered important risk factors for CHD. The aim of this study was to explore the correlation between CYP4A22 gene polymorphism and CHD susceptibility in the Chinese Han population. METHODS: We used SNPStats online software to complete the association analysis among 962 volunteers. False-positive report probability analysis was used to confirm whether a positive result is noteworthy. Haploview software and SNPStats were used for haplotype analysis and linkage disequilibrium. Multi-factor dimensionality reduction was applied to evaluate the interaction between candidate SNPs. RESULTS: In overall and some stratified analyses (male, age ≤ 60 years or CHD patients complicated with hypertension), CYP4A22-rs12564525 (overall, OR = 0.83, p-value is 0.042) and CYP4A22-rs2056900 (overall, OR = 1.22, p-value is 0.032) were associated with the risk of CHD. CYP4A22-4926581 was associated with increased CHD risk only in some stratified analyses. FPRP indicated that all positive results in our study are noteworthy findings. In addition, MDR showed that the single-locus model composed of rs2056900 is the best model for predicting susceptibility to CHD. CONCLUSION: There are significant associations between susceptibility to CHD and CYP4A22 rs12564525, and rs2056900.

Factors associated with the delay in informed consent procedures of patients with ST-segment elevation myocardial infarction and its influence on door-to-balloon time: a nationwide retrospective cohort study.

Background and Objectives: ST-segment elevation myocardial infarction (STEMI) is the deadliest and most time-sensitive acute cardiac event. However, failure to achieve timely informed consent is an important contributor to in-hospital delay in STEMI care in China. We investigated the factors associated with informed consent delay in patients with STEMI undergoing percutaneous coronary intervention (PCI) and the association between the delay and door-to-balloon time. Methods: We conducted a nationally representative retrospective cohort study using patient data reported by hospital-based chest pain centers from 1 January 2016 to 31 December 2020. We applied generalized linear mixed models and negative binomial regression to estimate factors independently predicting informed consent delay time. Logistic regressions were fitted to investigate the association of the informed consent delay time and door-to-balloon time, adjusting for patient characteristics. Results: In total, 257, 510 patients were enrolled in the analysis. Mean informed consent delay time was 22.4 min (SD = 24.0), accounting for 39.3% in door-to-balloon time. Older age (≥65 years) was significantly correlated with informed consent delay time (RR: 1.034, P = 0.001). Compared with ethnic Han patients, the minority (RR: 1.146, P < 0.001) had more likelihood to extend consent giving; compared with patients who were single, longer informed consent time was found in married patients (RR: 1.054, P = 0.006). Patients with intermittent chest pain (RR: 1.034, P = 0.011), and chest pain relief (RR: 1.085, P = 0.005) were more likely to delay informed consent. As for transfer modes, EMS (RR: 1.063, P < 0.001), transfer-in (RR: 1.820, P < 0.001), and in-hospital onset (RR: 1.099, P = 0.002) all had positive correlations with informed consent delay time compared to walk-in. Informed consent delay was significantly associated with prolonged door-to-balloon time (OR: 1.002, P < 0.001). Conclusion: Informed consent delay is significantly associated with the door-to-balloon time which plays a crucial role in achieving better outcomes for patients with STEMI. It is essential to shorten the delay time by identifying and intervening modifiable factors that are associated with shortening the informed consent procedure in China and other countries.

Role of pyroptosis in diabetic cardiomyopathy: an updated review.

Diabetic cardiomyopathy (DCM), one of the common complications of diabetes, presents as a specific cardiomyopathy with anomalies in the structure and function of the heart. With the increasing prevalence of diabetes, DCM has a high morbidity and mortality worldwide. Recent studies have found that pyroptosis, as a programmed cell death accompanied by an inflammatory response, exacerbates the growth and genesis of DCM. These studies provide a theoretical basis for exploring the potential treatment of DCM. Therefore, this review aims to summarise the possible mechanisms by which pyroptosis promotes the development of DCM as well as the relevant studies targeting pyroptosis for the possible treatment of DCM, focusing on the molecular mechanisms of NLRP3 inflammasome-mediated pyroptosis, different cellular pyroptosis pathways associated with DCM, the effects of pyroptosis occurring in different cells on DCM, and the relevant drugs targeting NLRP3 inflammasome/pyroptosis for the treatment of DCM. This review might provide a fresh perspective and foundation for the development of therapeutic agents for DCM.

Role of CYP19A1 Loci (rs28757157 and rs3751591) with Ischemic Stroke Risk in the Chinese Han Population.

Introduction: Ischemic stroke (IS) is a multifactorial and polygenic disease, which is affected by genetic factors. In this study, we explored the role of CYP19A1 single nucleotide polymorphisms (SNPs) in IS in the Chinese population. Methods: 1302 subjects (651 controls and 651 cases) were recruited in this case-control study. Four candidate SNPs (rs28757157 C/T, rs3751592 C/T, rs3751591 G/A, rs59429575 C/T) of CYP19A1 were selected by the 1000 genomes project database. The association between CYP19A1 SNPs and IS risk was assessed using logistic regression analysis with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis further verified the positive results. The interaction of SNP-SNP was analyzed by multi-factor dimensionality reduction (MDR) to predict is risk. Results: In the research, CYP19A1 loci (rs28757157 and rs3751591) were associated with the occurrence of IS. The two variants conferred an increased susceptibility to IS in the subjects aged over 60 years old, smokers and drinkers. Rs28757157 was related to the risk of IS in females, non-smokers and subjects with BMI less than 24, while rs59429575 was related to the risk of IS in males and subjects with BMI greater than 24. Conclusion: The study revealed that there is a significant association between CYP19A1 loci (rs28757157 and rs3751591) and IS risk in the Chinese Han population, providing a theoretical basis for further exploring its specific role in the pathogenesis of IS.

CYP4V2 rs56413992 C > T was associated with the risk of coronary heart disease in the Chinese Han population: a case-control study.

PURPOSE: The research aimed to detect the association between single nucleotide polymorphisms (SNPs) in CYP4V2 gene and coronary heart disease (CHD) risk. METHODS: This case-control study included 487 CHD subjects and 487 healthy individuals. Logistic regression was performed to analyze the connection between five SNPs in CYP4V2 (rs1398007, rs13146272, rs3736455, rs1053094, and rs56413992) and CHD risk, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the connection. RESULTS: As a result, we found that rs56413992 T allele (OR = 1.36, 95% CI = 1.09-1.70, p = 0.007) and CT genotype (OR = 1.40, 95% CI = 1.06-1.83, p = 0.017) were significantly associated with an increased risk of CHD in the overall analysis. Precisely, rs56413992 was linked to an elevated risk of CHD in people aged > 60, males, smokers and drinkers. The study also indicated that rs1398007 was linked to an increased CHD risk in drinkers. In addition, rs1053094 was correlated with a decreased risk of CHD complicated with diabetes mellitus (DM), and rs1398007 was correlated with a decreased risk of CHD complicated with hypertension (HTN). CONCLUSION: This study was the first to experimentally demonstrate that CYP4V2 rs56413992 was associated with the risk of CHD, which will provide a certain reference for revealing the pathogenesis of CHD.

Genetic Variants of CYP4F2 Associated with Ischemic Stroke Susceptibility in the Han Population from Southern China.

Background: The pathophysiological mechanism of ischemic stroke is complex. Traditional risk factors cannot fully or only partially explain the occurrence and development of IS. Genetic factors are getting more and more attention. Our study aimed to explore the association between CYP4F2 gene polymorphism and susceptibility to IS. Methods: A total of 1322 volunteers were enrolled to perform an association analysis through SNPStats online software. Using FPRP (false-positive report probability) to detect whether the result is a noteworthy finding. The interaction of SNP-SNP in IS risk was assessed by multi-factor dimensionality reduction. Statistical analysis of this study was mainly completed by SPSS 22.0 software. Results: Mutant allele "A" (OR = 1.24) and genotype "AA" (OR = 1.49) or "GA" (OR = 1.26) of CYP4F2-rs2108622 are risk genetic factors for IS. Rs2108622 is significantly associated with an increased risk of IS among subjects who are females, aging >60 years old, with BMI ≥24 kg/m2, and smoking or drinking volunteers. CYP4F2-rs3093106 and -rs3093105 are associated with susceptibility to IS among smoking, drinking subjects, or IS patients complicated with hypertension. Conclusion: CYP4F2-rs2108622, -rs3093106, and -rs3093105 are associated with an increased risk of IS.

Metoprolol Protects Against Arginine Vasopressin-Induced Cellular Senescence in H9C2 Cardiomyocytes by Regulating the Sirt1/p53/p21 Axis.

Cardiomyocyte senescence is involved in the pathological mechanism of cardiac diseases. Metoprolol is a ß1 receptor blocker used for the treatment of hypertension. Recent studies show that Metoprolol can protect cardiomyocytes against ischemia injury. The present study aims to investigate the protective effects of Metoprolol against arginine vasopressin (AVP)-induced cellular senescence in cultured cardiomyocytes. The cell proliferation assay and cytotoxicity lactate dehydrogenase assay showed that the highest tolerated dosage of Metoprolol in H9C2 cardiomyocytes was optimized as 10 µM. The enzyme-linked immunosorbent assay showed that Metoprolol significantly ameliorated the elevated level of the DNA oxidation product 8-hydroxy-2 deoxyguanosine. Metoprolol also decreased the percentage of senescence-associated ß-galactosidase positive cells and improved the telomerase activity under AVP exposure. Moreover, treatment with Metoprolol ameliorated the decreased intracellular nicotinamide phosphoribosyltransferase activity, nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD+/NADPH) ratio, and Sirtuin1 activity in cardiomyocytes by AVP. Finally, Metoprolol was able to downregulate the AVP-induced expression of acetylated p53 and p21. Taken together, our data reveal that Metoprolol protected the cardiomyocytes from AVP-induced senescence.

Two new triterpenoid glycosides from leaves of Cyclocarya paliurus.

Two dammarane glycosides (1-2) were isolated from the leaves of Cyclocarya paliurus. The structures of new compounds were established by application of spectroscopic methods, including one-dimensional and two-dimensional NMR, HRESIMS, and chemical hydrolysis. When evaluated against seven human cancer cell lines, the two compounds exhibited selective cytotoxicity to MCF-7 cells.[Formula: see text].

Sustained-Release Ivabradine Hemisulfate in Patients With Systolic Heart Failure.

BACKGROUND: Ivabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily. OBJECTIVES: This study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF. METHODS: Patients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32. RESULTS: We randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm. CONCLUSIONS: The present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082).

[Construction of eukaryotic recombinant plasmid of periodic Brugia malayi CPI gene and its immunity].

OBJECTIVE: To observe the immune responses elicited in BALB/c mice by DNA vaccine encoding cysteine protease inhibitor (CPI) of periodic Brugia malayi cloned in vector pcDNA3.1. METHODS: Specific primers were designed on the basis of known sequences of CPI gene from periodic B. malayi. The desired gene fragment was amplified by PCR from cDNA, inserted into cloning vector, pGEM-T, and sub-cloned into pcDNA3.1 to construct pcDNA3.1-BmCPI Forty-eight mice were randomly divided into 4 groups, i.e. normal control group, pcDNA3.1(+) group, pcDNA3.1-BmCPI group, and pcDNA3.1-BmCPI/CpG group injected with PBS 100 microl, pcDNA3.1 100 microg, pcDNA3.1-BmCPI 100 microg and pcDNA3.1-BmCPI 100 microg+CpG 30 microg, respectively on left hind leg of each mouse. All mice received three immunizations with 2-week interval. At the 4th week after the last immunization the muscle around injection spot was collected, in which the level of BmCPI mRNA was detected by RT-PCR. The stimulation index (SI) of spleen lymphocytes was measured by MTI method and the levels o f secreted IL-4 and IFN-gamma in serum were detected by ELISA. RESULTS: The recombinant plasmid pcDNA3.1-BmCPI was constructed and the length of the gene fragment was 621 bp. The results showed that BmCPI gene in the muscle of the immunized mice was detected by PCR. At the 4th and 6th weeks after immunization, the SI of the two immunized groups was significantly higher than normal control group and pcDNA3.1(+) group (53.789 +/- 1.937, 59.735 +/- 4.139, and 61.975 +/- 1.029) (P < 0.05). No significant difference existed between pcDNA3.1BmCPI group and pcDNA3.1-BmCPI/CpG group (P > 0.05). Serum IFN-gamma in pcDNA3.1-BmCPI group and pcDNA3.1-BmCPI/ CpG group increased from the 2nd to the 6th week after the last immunization with the value of 69.544 +/- 3.145 and 106.069 +/- 7.518, 120.019 +/- 5.968 and 136.229 +/- 7.198, 149.109 +/- 2.700 and 178.429 +/- 1.126, respectively. The levels of IFN-gamma in serum from the immunized mice were significantly higher than those of normal control group and pcDNA3.1(+) group (28.264 +/- 1.129, 35.179 +/- 1.029, and 40.110 +/- 1.176, respectively) (P < 0.05). There was a significant difference between the two immunized groups at the 2nd and the 6th weeks after the last immunization (P < 0.05). The level of IL-4 in serum from the immunized mice was significantly higher than those of normal control group and pcDNA3.1(+) group at the 4th and the 6th weeks after the last immunization (P < 0.05). No significant difference was noted in IL-4 level between pcDNA3.1-BmCPI group and pcDNA3.1-BmCPI/CpG group (P > 0.05). CONCLUSION: The recombinant eukaryotic plasmid pcDNA3.1-BmCPI was transcribed in vivo and elicited immune responses in mice.

LRVRG: a local region-based variational region growing algorithm for fast mandible segmentation from CBCT images.

OBJECTIVES: To segment the mandible from cone-beam computed tomography (CBCT) images efficiently and accurately for the 3D mandible model is essential for subsequent research and diagnosis. METHODS: This paper proposes a local region-based variational region growing algorithm, which integrates local region and shape prior to segment the mandible accurately. Firstly, we select initial seeds in the CBCT image and then calculate candidate point sets and the local region energy function of each point. If a point reduces the energy, it is selected to be a pixel of the foreground region. By multiple iterations, the mandible segmentation of the slice can be obtained. Secondly, the segmented result of the previous slice is adopted as the shape prior to the next slice until all of the slices in CBCT are segmented. At last, the final mandible model is reconstructed by the Marching Cubes algorithm. RESULTS: The experimental results on CBCT datasets illustrate the LRVRG algorithm can obtain satisfied 3D mandible models from CBCT images and it can solve the fuzzy problem effectively. Furthermore, quantitative comparisons with other methods demonstrate the proposed method achieves the state-of-the-art performance in mandible segmentation. CONCLUSIONS: Experiments demonstrate that our method is efficient and accurate for the mandible model segmentation.

The Number of Patients with Acute Myocardial Infarction Decreased and Door-to-Balloon Time Delayed in COVID-19.

BACKGROUND: At present, COVID-19 is sweeping the world, and all countries are actively responding. During the COVID-19 epidemic, the treatment of patients with acute myocardial infarction (AMI) may be affected. METHODS: We reviewed data of patients with AMI from January 23 to April 23, 2020 (2020), and January 23 to April 23, 2019 (2019), who were admitted to two hospitals from Southern China. We collected clinical characteristics, comorbidities, treatment, prognosis, and key time segments to analyze. RESULTS: The total number of patients that had been diagnosed with AMI in the two hospitals was 218 in 2020 and 260 in 2019. The number of AMI patients that were admitted to hospitals per day decreased in 2020. The percentage of patients with AMI who refused hospitalization in 2020 was significantly higher than that in 2019 (5.0% vs 1.5%, p=0.028). There is no statistical difference in symptoms of the first medical contact (S2FMC) time between 2020 and 2019 (p=0.552). Door-to-balloon (D2B) time of ST-elevation myocardial infarction (STEMI) patients who were treated with a primary percutaneous coronary intervention (pPCI) in 2020 was 79 (63.75-105.25) mins, while D2B time in 2019 was 57.5 (41.5-76.5) mins, which was statistically different from the two groups. CONCLUSIONS: COVID-19 had an impact on the number of AMI patients who were admitted to hospitals and the time of treatment. During the COVID-19 epidemic, the number of AMI patients that were admitted to hospitals per day was decreased, while the percentage of AMI patients that refused therapy in these two hospitals increased, and the D2B time of STEMI patients was also delayed.

MiR-30d inhibits cardiomyocytes autophagy promoting ferroptosis after myocardial infarction.

BACKGROUND: To investigate the effect of microRNA-30d (miR-30d) on autophagy and reveal the mechanism of autophagy promoting ferroptosis in H9C2 cells. METHODS: First, we detected miR-30d expression of myocardial tissue in the sham and myocardial infarction (MI) group, and then analyzed by biochemical analysis and luciferase Genetic experiments to confirm its downstream target gene of. After using Lentivirus-ATG5 (LV-sh-ATG5) to effectively inhibit autophagy, in order to further clarify the possible mechanism of autophagy leading to ferroptosis in H9C2 cells, we have tested the relevant indicators ferroptosis. RESULTS: We first found that miR-30d expression was down-regulated in myocardial tissue after MI, while autophagy increased, and autophagy was reduced when miR-30d was overexpressed, and then analyzed by biochemical analysis and luciferase Genetic experiments confirmed that ATG5 was a downstream target gene of miR-30d. After using Lentivirus-ATG5 (LV-shATG5) to effectively inhibit autophagy and up-regulate the expression of FTH1 and GPX4 in H9C2 cells, reduce the content of MDA, increase the content of GSH, and increase the activity of GPX4, suggesting that autophagy after MI may promote ferroptosis in H9C2 cells. CONCLUSIONS: The expression of miR-30d decreased in cardiomyocytes after MI and which can inhibit autophagy by binding to ATG5. Furthermore, autophagy after MI may promote ferroptosis.