MiR-378 Inhibits Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting AKT2.

Cardiomyocyte hypertrophy plays a crucial role in heart failure development, potentially leading to sudden cardiac arrest and death. Previous studies suggest that micro-ribonucleic acids (miRNAs) show promise for the early diagnosis and treatment of cardiomyocyte hypertrophy.To investigate the miR-378 expression in the cardiomyocyte hypertrophy model, reverse transcription-polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence tests were conducted in angiotensin II (Ang II)-induced H9c2 cells and Ang II-induced mouse model of cardiomyocyte hypertrophy. The functional interaction between miR-378 and AKT2 was studied by dual-luciferase reporter, RNA pull-down, Western blot, and RT-qPCR assays.The results of RT-qPCR analysis showed the downregulated expression of miR-378 in both the cell and animal models of cardiomyocyte hypertrophy. It was observed that the introduction of the miR-378 mimic inhibited the hypertrophy of cardiomyocytes induced by Ang II. Furthermore, the co-transfection of AKT2 expression vector partially mitigated the negative impact of miR-378 overexpression on Ang II-induced cardiomyocytes. Molecular investigations provided evidence that miR-378 negatively regulated AKT2 expression by interacting with the 3' untranslated region (UTR) of AKT2 mRNA.Decreased miR-378 expression and AKT2 activation are linked to Ang II-induced cardiomyocyte hypertrophy. Targeting miR-378/AKT2 axis offers therapeutic opportunity to alleviate cardiomyocyte hypertrophy.

Effect of electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen for diabetic foot ulcers.

Diabetic foot ulcers were a significant complication of diabetes and were accompanied by delayed wound healing. To compare the effect of topical application electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) dressing with alginate dressing when treating diabetic foot ulcers (DFUs). A single-center, prospective, randomized, patient-blinded clinical trial was conducted from July 1, 2023, to December 26, 2023. The clinical trial registration was completed on August 28, 2023 (ClinicalTrials.gov Identifier: NCT06014437). The eligible patients with DFUs of 1-20 cm2 present for at least 1 month and with Wagner grade 1 or 2. They were randomized 1:1 to receive PLCL/Fg or alginate dressing. Participants received PLCL/Fg dressing 1-3 times per week or alginate dressing 3 times per week for 12 weeks. A total of 52 patients (33 men [63.5 %]; mean [SD] age, 63.1 [11.9] years; mean [SD] diabetes time, 8.3 [4.6] years) with DFUs were assessed for this study. The DFUs classified as Wagner grade 1 or 2 (mean [SD] ulcer area, 3.8 [3.2] cm2) were randomized to receive either the PLCL/Fg dressing (n = 26) or the alginate dressing (n = 26) for as long as 12 weeks. In this study, the incidence of complete healing included 22 patients (91.7 %) in the PLCL/Fg group and 14 (63.6 %) in the alginate group during the 12-week treatment period (P = 0.003). The treatment-related adverse events that occurred were 5 (20.8 %) in the PLCL/Fg group and 4 (18.1 %) in the comparator group. In this randomized clinical trial, PLCL/Fg dressing showed beneficial effects in DFUs treatment of wound surface reduction and regulating the wound microenvironment.

Sr2HgGe2OS6: A Hg-Based Oxychalcogenide Infrared Nonlinear Optical Material Exhibiting Favorable Balance between a Large Band Gap and Strong Second Harmonic Generation Response.

Currently, oxychalcogenides with mixed-anion groups that integrate the property advantages of oxides (wide optical band gap) and chalcogenides [strong second harmonic generation (SHG) response] through chemical substitution engineering have attracted widespread interest and are considered to be important candidates for infrared (IR) nonlinear optical (NLO) materials. Herein, the first Hg-based oxychalcogenide Sr2HgGe2OS6 with mixed anion [GeOS3] units has been successfully synthesized through a spontaneous crystallization method, which exhibits a favorable balance between the strong SHG response (0.7 × AgGaS2) and large optical band gap (2.9 eV). In addition, Sr2HgGe2OS6 shows high laser-induced damage threshold (LIDT, 2.1 × AgGaS2) as well as phase-matching (PM) performance. Theoretical calculations indicate that the Sr2HgGe2OS6 encompasses large birefringence of 0.128@2090 nm (3.3 × AgGaS2) and its SHG density mainly comes from [HgS4] tetrahedra and [GeOS3] units. This work not only demonstrates that Sr2HgGe2OS6 is a promising IR NLO material but also provides new ideas for the exploration of Hg-based oxychalcogenide IR NLO materials.

Oral micronized progesterone versus vaginal progesterone for luteal phase support in fresh embryo transfer cycles: a multicenter, randomized, non-inferiority trial.

STUDY QUESTION: Does oral micronized progesterone result in a non-inferior ongoing pregnancy rate compared to vaginal progesterone gel as luteal phase support (LPS) in fresh embryo transfer cycles? SUMMARY ANSWER: The ongoing pregnancy rate in the group administered oral micronized progesterone 400 mg per day was non-inferior to that in the group administered vaginal progesterone gel 90 mg per day. WHAT IS KNOWN ALREADY: LPS is an integrated component of fresh IVF, for which an optimal treatment regimen is still lacking. The high cost and administration route of the commonly used vaginal progesterone make it less acceptable than oral micronized progesterone; however, the efficacy of oral micronized progesterone is unclear owing to concerns regarding its low bioavailability after the hepatic first pass. STUDY DESIGN, SIZE, DURATION: This non-inferiority randomized trial was conducted in eight academic fertility centers in China from November 2018 to November 2019. The follow-up was completed in April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1310 infertile women who underwent their first or second IVF cycles were enrolled. On the day of hCG administration, the patients were randomly assigned to one of three groups for LPS: oral micronized progesterone 400 mg/day (n = 430), oral micronized progesterone 600 mg/day (n = 440) or vaginal progesterone 90 mg/day (n = 440). LPS was started on the day of oocyte retrieval and continued till 11-12 weeks of gestation. The primary outcome was the rate of ongoing pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: In the intention-to-treat analysis, the rate of ongoing pregnancy in the oral micronized progesterone 400 mg/day group was non-inferior to that of the vaginal progesterone gel group [35.3% versus 38.0%, absolute difference (AD): -2.6%; 95% CI: -9.0% to 3.8%, P-value for non-inferiority test: 0.010]. There was insufficient evidence to support the non-inferiority in the rate of ongoing pregnancy between the oral micronized progesterone 600 mg/day group and the vaginal progesterone gel group (31.6% versus 38.0%, AD: -6.4%; 95% CI: -12.6% to -0.1%, P-value for non-inferiority test: 0.130). In addition, we did not observe a statistically significant difference in the rate of live births between the groups. LIMITATIONS, REASONS FOR CAUTION: The primary outcome of our trial was the ongoing pregnancy rate; however, the live birth rate may be of greater clinical interest. Although the results did not show a difference in the rate of live births, they should be confirmed by further trials with larger sample sizes. In addition, in this study, final oocyte maturation was triggered by hCG, and the findings may not be extrapolatable to cycles with gonadotropin-releasing hormone agonist triggers. WIDER IMPLICATIONS OF THE FINDINGS: Oral micronized progesterone 400 mg/day may be an alternative to vaginal progesterone gel in patients reluctant to accept the vaginal route of administration. However, whether a higher dose of oral micronized progesterone is associated with a poorer pregnancy rate or a higher rate of preterm delivery warrants further investigation. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a grant from the National Natural Science Foundation of China (82071718). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the number ChiCTR1800015958. TRIAL REGISTRATION DATE: May 2018. DATE OF FIRST PATIENT'S ENROLMENT: November 2018.

Antimicrobial resistance and molecular epidemiology of carbapenem-resistant Escherichia coli from urinary tract infections in Shandong, China / Resistencia a los antimicrobianos y epidemiología molecular de Escherichia coli resistente a carbapenémicos procedente de infecciones del tracto urinario en Shandong, China

Objectives: Urinary tract infection (UTI) is one of the most common extraintestinal infections, and uropathogenic Escherichia coli (UPEC) is the main cause of UTIs. However, the ability to treat UTI has been compromised by the increase in antimicrobial resistance, especially carbapenem resistance. Here, we aimed to characterize the antimicrobial resistance and molecular epidemiology of carbapenem-resistant UPEC isolated in Shandong, China. Methods: In total, 17 carbapenem-resistant UPEC (CR-UPEC) isolates were collected from July 2017 to May 2020 in the Shandong Provincial Hospital. Whole-genome sequencing and bioinformatics analyses were performed to understand the molecular epidemiology of CR-UPEC. Phylogenetic groups, drug resistance genes, biofilm formation, and virulence-related gene profiles of the isolates were analyzed. Plasmid profiling and conjugation assay were performed to evaluate the ability to transfer carbapenem resistance-related genes to other E. coli isolates. Biofilm formation was also evaluated, as it is important for the persistence of infectious diseases. Results: We observed that 15 out of 17 CR-UPEC strains were blaNDM producers, among which 4 isolates could transfer blaNDM to recipient cells. The predominant sequence type was ST167 (6/17), followed by ST410 (3/17). The most prevalent phylogenetic group was phylogenetic group A (10/17), followed by phylogenetic group C (3/17). One isolate was resistant to polymyxin, which was caused by the carriage of a transferable plasmid harboring mcr-1. Statistical analysis did not reveal any significant difference in the carriage rate of fimbriae-coding genes between strong and weak biofilm producers. Conclusions: Our observations may assist in developing new therapeutic methods for drug-resistant organisms.(AU)

Antimicrobial resistance and molecular epidemiology of carbapenem-resistant Escherichia coli from urinary tract infections in Shandong, China.

OBJECTIVES: Urinary tract infection (UTI) is one of the most common extraintestinal infections, and uropathogenic Escherichia coli (UPEC) is the main cause of UTIs. However, the ability to treat UTI has been compromised by the increase in antimicrobial resistance, especially carbapenem resistance. Here, we aimed to characterize the antimicrobial resistance and molecular epidemiology of carbapenem-resistant UPEC isolated in Shandong, China. METHODS: In total, 17 carbapenem-resistant UPEC (CR-UPEC) isolates were collected from July 2017 to May 2020 in the Shandong Provincial Hospital. Whole-genome sequencing and bioinformatics analyses were performed to understand the molecular epidemiology of CR-UPEC. Phylogenetic groups, drug resistance genes, biofilm formation, and virulence-related gene profiles of the isolates were analyzed. Plasmid profiling and conjugation assay were performed to evaluate the ability to transfer carbapenem resistance-related genes to other E. coli isolates. Biofilm formation was also evaluated, as it is important for the persistence of infectious diseases. RESULTS: We observed that 15 out of 17 CR-UPEC strains were blaNDM producers, among which 4 isolates could transfer blaNDM to recipient cells. The predominant sequence type was ST167 (6/17), followed by ST410 (3/17). The most prevalent phylogenetic group was phylogenetic group A (10/17), followed by phylogenetic group C (3/17). One isolate was resistant to polymyxin, which was caused by the carriage of a transferable plasmid harboring mcr-1. Statistical analysis did not reveal any significant difference in the carriage rate of fimbriae-coding genes between strong and weak biofilm producers. CONCLUSIONS: Our observations may assist in developing new therapeutic methods for drug-resistant organisms.

Preclinical animal study of electrospun poly (l-lactide-co-caprolactone) and formulated porcine fibrinogen for full-thickness diabetic wound regeneration.

Diabetic foot ulcer is one of the most serious chronic complications of diabetes mellitus. It may lead to amputation of the lower extremities for diabetics. Our study was to evaluate the effect of electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) wound dressing on animal wound model. A blend ratio of PLCL/Fg scaffold was 4 (PLCL):1 (Fg). The scanning electron microscopy findings showed that the fibers' diameter was 122.5 ± 80.3 nm, and the tensile strength was 9.2 ± 0.2 MPa. In-vivo study of the hog normal model demonstrated that PLCL/Fg dressing had better biocompatibility, degradability, and ability to restore the skin's normal structure. We evaluated the wound healing processes in the rat diabetic model by macroscopic observation and histological observation at 1, 2, and 3 post-operation weeks. In our study, the PLCL/Fg group performed better 3 weeks after surgery, in terms of macroscopic healing and scarring. After surgery, the PLCL/Fg group showed better fibroblast accumulation, tissue granulation, and collagen expression than the control group. Topical treatment with PLCL/Fg dressing effectively enhanced wound healing in both normal and hyperglycemic conditions, suggesting that it may possess wound-healing potential.

The Kurtz-Perry Powder Technique Revisited: A Study of the Effect of Reference Selection on Powder Second-Harmonic Generation Response.

The accurate evaluation of nonlinear optical (NLO) coefficient, the main parameter affecting light conversion efficiency, plays a crucial role in the development of NLO materials. The Kurtz-Perry powder technique can evaluate second-harmonic generation (SHG) intensity in pristine powder form, saving a significant amount of time and energy in the preliminary screening of materials. However, the Kurtz-Perry method has recently been subject to some controversy due to the limitations of the Kurtz-Perry theory and the oversimplified experimental operation. Therefore, it is very meaningful to revisit and develop the Kurtz-Perry technique. In this work, on the basis of introducing the light scattering effect into the original Kurtz-Perry theory, the theoretical expression of second-harmonic generation intensity with respect to band gap and refractive index are analyzed. In addition, the reference-dependent SHG measurements were carried out on polycrystalline LiB3O5 (LBO), AgGaQ2 (Q = S, Se), BaGa4Q7 (Q = S, Se), and ZnGeP2 (ZGP), and the results of SHG response emphasize the importance of using appropriate references to the Kurtz-Perry method. In order to obtain reliable values of nonlinear coefficients, two criteria for selecting a reference compound were proposed: (1) it should possess a band gap close to that of the sample to be measured and (2) it should possess a refractive index close to that of the sample to be measured. This work might shed light on improvements in accuracy that can be made for effective NLO coefficients obtained using the Kurtz-Perry method.

Characterization of the microenvironment of diabetic foot ulcers and potential drug identification based on scRNA-seq.

Background: Diabetes foot ulcers (DFUs) are a type of foot infection, ulcer, and/or deep tissue destruction caused by neuropathy and vascular disease in the distal extremities of diabetic patients. Its pathogenesis and its microenvironment are not entirely understood. Methods: Initially, the GSE165816 data set from the GEO database was utilized for single cell analysis to reveal the microenvironment and functional status of DFUs. The GSE199939 RNA-seq data set was utilized for external validation. On the basis of the logistic regression machine learning algorithm (OCLR), pseudo time series analysis, dryness index analysis, and drug target gene analysis were then performed. By constructing drug-gene and gene-gene networks, we can locate the most recent DFUs treatments. Finally, immunofluorescence technology was used to detect the cell-related markers of the DFUs microenvironment, and qPCR was used to detect the expression of drug targets in DFUs. Results: Firstly, we used the Cell Maker database to obtain information about human cells and related gene markers, and manually reviewed a total of 45 kinds of cells and maker information that may appear in the DFUs microenvironment, which were divided into 17 cell clusters after annotation. Subsequently, we counted the proportions of DM and DFUs in different types of cells, and the results showed that the proportions of macrophages, white blood cells, and monocytes were higher in patients with DFUs, while the proportions of pluripotent stem cells and stromal cells were higher in patients with DM. The Pseudo-time series analysis of cells in DFUs showed that the differentiation pathways of immune cells, mesenchymal cells and stem cells were similar in the three states, while the other cells were distributed in different stages. At the level of a single cell, the scores of both multipotential stem cells and hematopoietic stem cells were significantly lower in DFU healing and non-healing than in DM. Additionally, the highly expressed genes in DFU were chosen as drug targets. We identified seven potential target genes and discovered twenty drugs with high significance. Finally, the colocalization relationship between CD19, ITGAM, and HLA-DR expression in monocytes and macrophages of DFU skin tissue and healthy subjects was analyzed by laser confocal microscopy with the immunofluorescence triple labeling method. The results showed that the expressions of CD19, ITGAM, and HLA-DR in the skin of DFUs were significantly higher than those in the skin of healthy subjects, and the co-localization relationship was significant in DFUs. Conclusion: This study can serve as a resource for the treatment of DFUs.

Role of M1 macrophages in diabetic foot ulcers and related immune regulatory mechanisms.

Objectives: Diabetes foot ulcers (DFUs) are characterized by immune infiltration of M1 macrophages observed in foot skin, in which immune-associated genes (IRGs) play a prominent role. The precise expression of IRGs as well as any possible regulatory mechanisms that could be present in DFUs is yet unknown. Methods: The sequencing data of single-cell RNA (scRNA) in the foot skin of patients with DFUs were analyzed, screening out the cluster marker genes of foot skin obtained from the ImmPort database. IRG activity was assessed with the AUCell software package. The IRGs of DFUs were explored by analyzing the batch sequencing dataset of DFU skin tissue. HumanTFDB was adopted to identify relevant regulatory transcription factors (TFs). The STRING dataset was used to build the main TF protein-protein interaction networks. WB and immunofluorescence methods were used to verify M1 macrophage-related immune regulators. Results: There were 16 clusters found: SMC1, fibro, t-lympho, he fibro, vasendo, baselkera, diffkera, SMC2, M1 macro, M2 macro, sweet/seba, B-Lympho, Melanio, lymphendo, plasma, and Schwann. M1 and M2 macrophages both had considerably higher AUC ratings than patients with DFUs compared to other sub-populations of cells. The proportion of M1 macrophages was the highest in the non-healing group. According to scRNA analysis and batch sequencing data by GO and KEGG, DEGs were enriched in immune response. Some 106 M1 macro-IRGs were finally identified and 25 transcription factors were revealed as associated with IRG expression. The PPI network indicated NFE2L2, REL, ETV6, MAF, and NF1B as central transcription factors. Conclusion: Based on the bio-informatics analysis of scRNA and high-throughput sequencing data, we concluded that M1 macrophages may serve as the influencing factor of DFUs' non-union. In addition, NFE2L2 could be involved in the regulation of IRG expression within M1 macrophages.

Transcollateral Recanalization of an Occluded Superior Mesenteric Artery.

OBJECTIVE: To report the technique of transcollateral retrograde recanalization of a superior mesenteric artery flush occlusion. METHODS: The technique of a patient undergoing transcollateral retrograde recanalization for acute symptomatic superior mesenteric artery flush occlusion was reviewed and presented. Other adjunctive methods to facilitate the endovascular treatment of the superior mesenteric artery total occlusion lesion were also compared and discussed. RESULTS: The patient was a 47-year-old woman, acute onset of symptomatic chronic mesenteric ischemia with flush occlusion of the superior mesenteric artery which was unable to be revascularized in a routine operation. A collateral was found to connect celiac artery and superior mesenteric artery (gastroduodenal arch). The guidewire was retrograde crossed the occluded lesion via this collateral and recaptured by the catheter from the same single brachial sheath followed by balloon angioplasty and stent implantation. The patient recovered well and the symptoms completely disappeared after the procedure. CONCLUSION: The technique of retrograde recanalization through collateral pathway is an applicable alternative option for patients with superior mesenteric artery flush occlusion who have failed attempts by conventional antegrade approaches.

A Multicenter Assessment of Anatomic Suitability for Iliac Branched Devices in Eastern Asian Patients With Unilateral and Bilateral Aortoiliac Aneurysms.

Objective: This study aims to assess the suitability of four types of commercial iliac branch device systems to treat Eastern Asian abdominal aortic aneurysm (AAA) patients with bilateral or unilateral common iliac artery aneurysms (CIAAs). Methods: Patients with a coexisting AAA and a unilateral or bilateral CIAAs who underwent endovascular aneurysm repair (EVAR) at two tertiary centers in China from 2015 to 2017 were reviewed. Morphology of lesions was measured and the anatomic suitability for Cook iliac branch device (IBD), Gore iliac branch endoprosthesis (IBE), Lifetech iliac branch stent graft (IBSG), and Jotec IBD was evaluated according to the latest instructions for use. Results: Seventy-six patients with AAA were enrolled, including 35 bilateral CIAAs, 41 unilateral CIAAs. A hundred and eleven lesions were investigated aggregately: 16.2, 28.8, 21.6, and 19.8% met the criteria for Cook IBD, Gore IBE, Lifetech IBSG, and Jotec IBD, respectively. A total of 34 (44.7%) patients could be treated for at least one lateral lesion. The diameter of the internal iliac artery (IIA) was the most common restriction for IBD application. Additionally, the IIA diameter of lesions in the bilateral group was significantly larger compared with the unilateral group (P < 0.001). Based on the anatomical characteristics alone, it is likely that IBDs will be more suitable for unilateral lesions than bilateral ones (P < 0.05). However, there was no difference between the suitability for patients with unilateral or bilateral CIAAs (P > 0.05). Conclusions: Less than half of Eastern Asian patients with aortoiliac aneurysms were eligible for IBD application. This was primarily due to the IIA diameter failing to meet the criteria. And thus, the suitability of lesions in bilateral group was significantly lower than that in the unilateral group. Aiming to expand the indications and optimize the design of the iliac branch devices, IIA diameter and the anatomical characteristics of the bilateral lesions should be considered deliberately.

Identifying prognostic biomarkers in endometrial carcinoma based on ceRNA network.

PURPOSE: Endometrial carcinoma (EC), a common gynecological malignancy with high incidence, affects the mental and physical health of women. Mounting evidence shows that long noncoding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) have instrumental roles in various biological processes associated with the pathogenesis of EC. In this research, we intend to further study the mechanism of EC and the potential predictive markers of EC. METHODS: First, we obtained original data of EC RNA transcripts from The Cancer Genome Atlas database and performed differential analysis. Subsequently, according to the miRcode online software, relationship pairs of lncRNA-miRNA were constructed, and miRNA-mRNA pairs were established based on miRDB, TargetScan, and miRTarBase. Then, we constructed the competing endogenous RNA (ceRNA) network based on lncRNA-miRNA and miRNA-mRNA pairs. To further explain the function of the ceRNA network and explore the potential prognostic markers, functional enrichment analysis, and survival analysis were carried out. RESULTS: The research showed that there were 744 differential expression lncRNAs (DElncRNAs), 164 differential expression miRNAs (DEmiRNAs), and 2447 differential expression mRNAs (DEmRNAs) between EC tissues and normal tissues. Subsequently, we built 103 DEmiRNA-DEmRNA interaction pairs and 369 DElncRNA-DEmiRNA pairs. Then, we established the ceRNA network of EC, including 62 DElncRNAs, 26 DEmiRNAs, and 70 DEmRNAs. Moreover, 10 of 62 lncRNAs, 19 of 70 mRNAs, and 4 of 26 miRNAs that closely related to the survival of EC with P < .05 were obtained. Notably, based on this network, it was found that LINC00261-hsa-mir-31 pair and LINC00261-hsa-mir-211 target pairs could be used as the potential prognostic markers of EC. CONCLUSION: This research recommended an available basis for the molecular mechanism of EC and prognosis prediction, which could help guide the subsequent treatments and predict the prognosis for patients with EC.

Long-term outcomes of balloon-expandable bare stent as chimney stent in thoracic endovascular aortic repair for supra-aortic branches reconstruction.

BACKGROUND: To report the long-term outcomes of balloon-expandable bare stent (BEBS) as chimney stent (CS) in thoracic endovascular aortic repair (TEVAR) for supra-aortic branches reconstruction. METHODS: A total of 33 patients with thoracic aortic diseases underwent TEVAR using BEBSs as CSs for supra-aortic branches reconstruction in our center from 2010 to 2015. The demographics and procedural details were prospectively collected and retrospectively reviewed. All patients were followed up at 1, 3, 6 months and every 1 year thereafter. Postoperative complications and long-term outcomes were recorded. RESULTS: The technical success rate was 100%. A total of 36 BEBSs were utilized as CSs to reconstruct the supra-aortic branches during TEVAR. The rate of immediate endoleak was 42.4% (14/33), including 12 (36.4%) type Ia endoleaks and 2 (6.1%) type II endoleaks. Two of type Ia endoleaks were managed by balloon dilation and disappeared, while the rest were left with close follow-up. Two type II endoleaks were embolized by coils and excluded by a plug, respectively. One patient (3.0%) died 2 days after the procedure due to the acute rupture of aortic dissection. The mean follow-up time was 61.8 (ranged from 12 to 102) months. The unmanaged 10 type Ia endoleaks were closely observed during the follow-up, of which 7 disappeared at 1 year and 1 disappeared at 2 years. The rest 2 type Ia endoleaks existed without further dilation of the aorta. One patient (3.0%) was re-intervened for the increased false lumen due to the distal residual tears. The long-term mortality was 9.1% (3/33). All CSs kept patent till the end of follow-up. No other complications were found. CONCLUSIONS: The balloon-expandable stent (BES) is a feasible choice as CS for supra-aortic branches reconstruction with long-term patency during TEVAR. However, BEBS may be related to a higher rate of early endoleak.

Glucose-6-phosphate dehydrogenase mutant D306C has a higher inhibition rate for enzyme multiplied immunoassay of cholyglycine.

Glucose-6-phosphate dehydrogenase (G6PDH) has been used in enzyme multiplied immunoassay technique (EMIT) assays for detecting small molecule metabolites such as cholyglycine (CG). A key parameter for successful EMIT CG assay development is the inhibition rate of the G6PDH-CG conjugate, measured as the decrease in enzyme activity upon CG antibody binding. Several commonly used G6PDH cysteine mutants including A45C and K55C have been labeled with CG-maleimide derivative, but inhibition rates of are unsatisfactory. Herein, we investigated whether other mutation sites can achieve better inhibition rates. We generated eight cysteine mutants (K106C, Y155C, A201C, T258C, D306C, D375C, G426C, and D480C) of G6PDH, measured their inhibition rates, and evaluated the performance of the D306C mutant using EMIT CG assays. One of the eight mutants (D306C) displayed improved inhibition rate, whereas all others exhibited inhibition similar to or lower than that of A45C and K55C. The enhanced inhibition rate of D306C improved the EMIT CG assay calibration curve, using an Abbott c16000 automated biochemical analyzer, resulting in better repeatability, precision, and linearity than with K55C assays and a commercially available EMIT CG kit. The G6PDH mutant D306C has a higher inhibition rate in EMIT CG assays and improves assay performance.

Identification of Lysophosphatidylcholines and Sphingolipids as Potential Biomarkers for Acute Aortic Dissection via Serum Metabolomics.

OBJECTIVES: Acute aortic dissection (AAD) is a severe clinical emergency with a high mortality, and is easily misdiagnosed in its early stage. This study aimed at discovering serum metabolomic markers with the potential to diagnose AAD and distinguish between two subtypes of AAD. METHODS: Thirty-five patients with AAD, including 20 with Stanford type A and 15 with Stanford type B were enrolled in this study, together with 20 healthy controls. All patients with AAD were admitted within 72 h of onset. Serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and the data were analysed by principal component analysis and partial least squares discriminant analysis. RESULTS: A total of 17 metabolites differing between the control and AAD groups were finally screened and identified as lysophosphatidylcholines (LPC) and sphingolipids including sphinganine, phytosphingosine, sphingomyelin, and ceramide. Compared with those in the healthy control group, LPC levels were significantly lower in both the Stanford type A and type B AAD groups. Interestingly, sphingolipids, including sphinganine, phytosphingosine, and ceramide, were remarkably reduced in the Stanford type A AAD group, but not in the Stanford type B AAD group. Subgroup analysis showed that the changes in LPC and sphingolipid levels were unrelated to hypertension or gender. CONCLUSIONS: The present results indicate that LPCs and sphingolipids are significantly altered in patients with AAD, and several sphingolipids, such as sphinganine, phytosphingosine, and ceramide, were dramatically decreased in patients with Stanford type A AAD. A combination of these two families of metabolites could serve as a potential biomarker for the diagnosis of AAD and distinguishing between Stanford type A and Stanford type B.

Obstructive sleep apnea and risk of aortic dissection: A meta-analysis of observational studies.

Objectives Obstructive sleep apnea acts as a potential risk factor for the development of cardiovascular disease. We undertook collaborative meta-analyses to clarify the risk of aortic dissection among adults suffering obstructive sleep apnea. Methods A systematic search of the databases (PubMed, Embase, and Cochrane Library) was performed. Studies reporting on the association between obstructive sleep apnea and aortic dissection were included. Information on 424 cases of aortic dissection in 56,291 patients from one cohort, four case-controls, and two cross-sectional studies were included in this study. Results The summary suggested that patients with obstructive sleep apnea are associated with an overall significant 60% increase in the risk of aortic dissection, compared to unexposed patients (odds ratios 1.60; 95% confidence interval 1.01-2.53), with a significantly higher apnea-hypopnea index (mean difference 10.71; 95% confidence interval 7.46-13.96). Moreover, a greater relation was found between moderate-to-severe obstructive sleep apnea and aortic dissection (odds ratios 4.43; 95% confidence interval 2.59-7.59). Adverse outcomes obtained by sleep study such as oxygen desaturation index (mean difference 10.51; 95% confidence interval 7.54-13.48), average SaO2 (-1.36; 95% confidence interval -2.63 to -0.09), and minimum SaO2 (-3.63; 95% confidence interval -5.27 to -1.98) were correspondingly related to patients with aortic dissection. Conclusions Obstructive sleep apnea, especially moderate-to-severe obstructive sleep apnea, may impose an additional risk of suffering from aortic dissection with a potential mechanism including intermittent hypoxia.

Hypoperfusion Induced by Preconditioning Treadmill Training in Hyper-Early Reperfusion After Cerebral Ischemia: A Laser Speckle Imaging Study.

Exercise preconditioning induces neuroprotective effects during cerebral ischemia and reperfusion, which involves the recovery of cerebral blood flow (CBF). Mechanisms underlying the neuroprotective effects of re-established CBF following ischemia and reperfusion are unclear. The present study investigated CBF in hyper-early stage of reperfusion by laser speckle contrast imaging, a full-field high-resolution optical imaging technique. Rats with or without treadmill training were subjected to middle cerebral artery occlusion followed by reperfusion. CBF in arteries, veins, and capillaries in hyper-early stage of reperfusion (1, 2, and 3 h after reperfusion) and in subacute stage (24 h after reperfusion) were measured. Neurological scoring and 2,3,5-triphenyltetrazolium chloride staining were further applied to determine the neuroprotective effects of exercise preconditioning. In hyper-early stage of reperfusion, CBF in the rats with exercise preconditioning was reduced significantly in arteries and veins, respectively, compared to rats with no exercise preconditioning. Capillary CBF remained stable in the hyper-early stage of reperfusion, though it increased significantly 24 h after reperfusion in the rats with exercise preconditioning. As a neuroprotective strategy, exercise preconditioning reduced the blood perfusion of arteries and veins in the hyper-early stage of reperfusion, which indicated intervention-induced neuroprotective hypoperfusion after reperfusion onset.

Reduced Severity of Outcome of Recurrent Ipsilateral Transient Cerebral Ischemia Compared with Contralateral Transient Cerebral Ischemia in Rats.

BACKGROUND: To investigate whether prior transient ischemic attack (TIA) had a preconditioning effect on subsequent cerebral infarction in a rat model using middle cerebral artery occlusion (MCAO). METHODS: Thirty-six adult male Sprague-Dawley rats were divided into 3 groups: those with transient (5 minutes) left MCAO (left TIA) (n = 15), those with transient right MCAO (right TIA) (n = 15), and a sham operation group (n = 6). Seven days after the initial transient MCAO, rats in all groups underwent permanent left MCAO. After 24 hours, all rats underwent motor function measurement (the Garcia score and tilting plane test), magnetic resonance imaging, postmortem brain examination, and biomarkers of stroke. RESULTS: Following permanent MCAO, the Garcia score, the brain edema area of T2-weighted images, brain infarction volume, and the level of tumor necrosis factor α mRNA of the ipsilateral and contralateral TIA groups showed no significant difference. The angle of sliding off in the tilting plane test, the mean intensity of the brain edema area of T2-weighted images, levels of matrix metalloproteinase 9, interleukin-1ß, inducible nitric oxide synthase mRNA, and apoptosis-related proteins, BAX, and phosphorylated-p38, were lower in the ipsilateral TIA group compared with the contralateral TIA group. CONCLUSION: The main finding of this study was that a transient, mild, unilateral focus of cerebral ischemia (or TIA) in either the left or right hemisphere, which is then followed by a second unilateral severe and focal ischemic event, results in brain injury. The severity of the brain injury following this second ischemic event will be alleviated when the second insult is ipsilateral to the first TIA.

Increased methylation of human papillomavirus type 16 DNA is associated with the severity of cervical lesions in infected females from northeast China.

Hypermethylation of the cytosine-phosphate-guanine (CpG) sites located at the 3'-major capsid protein L1 (3'L1) and the long control region (LCR) of the human papillomavirus (HPV) genome may be associated with the progression of cervical cancer (CC). However, the methylation status of the LCR of HPV type 16 DNA remains to be elucidated in an infected Chinese population. The aim of the present study was to investigate the association between methylation of the HPV 16 L1 gene and LCR, and the severity of cervical lesions in infected female patients. Therefore, bisulfite modification, polymerase chain reaction amplification and sequencing were used to analyze 122 HPV 16-positive clinical cervical swabs obtained from patients in northeastern China. The proportion of methylated samples at each of the 7 CpG sites within the 3'-L1/5'-LCR and 5 CpG sites within the promoter region was significantly increased in patients with CC, compared with that observed in high-grade squamous intraepithelial lesions (HSIL) and normal tissue/low-grade intraepithelial lesions (LSIL) (χ2 test, P<0.01). The mean methylation frequencies of the CpG sites 7,089 and 7,143 exhibited an area under the curve value of 0.822 [95% confidence interval (CI)=0.733-0.911] for distinguishing CC from other lesions, 0.787 (95% CI=0.700-0.874) for distinguishing normal/LSIL from HSIL and CC, and 0.763 (95% CI=0.652-0.874) for distinguishing CC from HSIL. These results suggest that the methylation of CpG sites within the HPV 16 3'-L1 and LCR region is correlated with the severity of cervical lesions. Quantification of HPV DNA methylation in the L1 gene and promoter region appears to provide a promising novel marker for distinguishing between normal tissue/LSIL, HSIL and CC in a Chinese population.