Impeding DNA Break Repair Enables Oocyte Quality Control.

Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death can be triggered by defects in chromosome synapsis and recombination, which involve repair of DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oocyte quality control. Both physiological apoptosis and wholesale oocyte elimination in meiotic mutants require RNF212. RNF212 sensitizes oocytes to DSB-induced apoptosis within a narrow window as chromosomes desynapse and cells transition into quiescence. Analysis of DNA damage during this transition implies that RNF212 impedes DSB repair. Consistently, RNF212 is required for HORMAD1, a negative regulator of inter-sister recombination, to associate with desynapsing chromosomes. We infer that oocytes impede repair of residual DSBs to retain a "memory" of meiotic defects that enables quality-control processes. These results define the logic of oocyte quality control and suggest RNF212 variants may influence transmission of defective genomes.

Dzip1 is dynamically expressed in the vertebrate germline and regulates the development of Xenopus primordial germ cells.

Primordial germ cells (PGCs) are the precursors of sperms and oocytes. Proper development of PGCs is crucial for the survival of the species. In many organisms, factors responsible for PGC development are synthesized during early oogenesis and assembled into the germ plasm. During early embryonic development, germ plasm is inherited by a few cells, leading to the formation of PGCs. While germline development has been extensively studied, how components of the germ plasm regulate PGC development is not fully understood. Here, we report that Dzip1 is dynamically expressed in vertebrate germline and is a novel component of the germ plasm in Xenopus and zebrafish. Knockdown of Dzip1 impairs PGC development in Xenopus embryos. At the molecular level, Dzip1 physically interacts with Dazl, an evolutionarily conserved RNA-binding protein that plays a multifaced role during germline development. We further showed that the sequence between amino acid residues 282 and 550 of Dzip1 is responsible for binding to Dazl. Disruption of the binding between Dzip1 and Dazl leads to defective PGC development. Taken together, our results presented here demonstrate that Dzip1 is dynamically expressed in the vertebrate germline and plays a novel function during Xenopus PGC development.

How Do Environmental Toxicants Affect Oocyte Maturation Via Oxidative Stress?

In mammals, oogenesis initiates before birth and pauses at the dictyate stage of meiotic prophase I until luteinizing hormone (LH) surges to resume meiosis. Oocyte maturation refers to the resumption of meiosis that directs oocytes to advance from prophase I to metaphase II of meiosis. This process is carefully modulated to ensure a normal ovulation and successful fertilization. By generating excessive amounts of oxidative stress, environmental toxicants can disrupt the oocyte maturation. In this review, we categorized these environmental toxicants that induce mitochondrial dysfunction and abnormal spindle formation. Further, we discussed the underlying mechanisms that hinder oocyte maturation, including mitochondrial function, spindle formation, and DNA damage response.

MRNIP interacts with sex body chromatin to support meiotic progression, spermatogenesis, and male fertility in mice.

Meiosis has a principal role in sexual reproduction to generate haploid gametes in both sexes. During meiosis, the cell nucleus hosts a dynamic environment where some genes are transcriptionally activated, and some are inactivated at the same time. This becomes possible through subnuclear compartmentalization. The sex body, sequestering X and Y chromosomes during male meiosis and creating an environment for the meiotic sex chromosome inactivation (MSCI) is one of the best known and studied subnuclear compartments. Herein, we show that MRNIP forms droplet-like accumulations that fuse together to create a distinct subnuclear compartment that partially overlaps with the sex body chromatin during diplotene. We demonstrate that Mrnip-/- spermatocytes have impaired DNA double-strand break (DSB) repair, they display reduced sex body formation and defective MSCI. We show that Mrnip-/- undergoes critical meiocyte loss at the diplotene stage. Furthermore, we determine that DNA DSBs (induced by SPO11) and synapsis initiation (facilitated by SYCP1) precede Mrnip expression in testes. Altogether, our findings indicate that in addition to an emerging role in DNA DSB repair, MRNIP has an essential function in spermatogenesis during meiosis I by forming drop-like accumulations interacting with the sex body.

Loss of TDP-43 in male germ cells causes meiotic failure and impairs fertility in mice.

Meiotic arrest is a common cause of human male infertility, but the causes of this arrest are poorly understood. Transactive response DNA-binding protein of 43 kDa (TDP-43) is highly expressed in spermatocytes in the preleptotene and pachytene stages of meiosis. TDP-43 is linked to several human neurodegenerative disorders wherein its nuclear clearance accompanied by cytoplasmic aggregates underlies neurodegeneration. Exploring the functional requirement for TDP-43 for spermatogenesis for the first time, we show here that conditional KO (cKO) of the Tardbp gene (encoding TDP-43) in male germ cells of mice leads to reduced testis size, depletion of germ cells, vacuole formation within the seminiferous epithelium, and reduced sperm production. Fertility trials also indicated severe subfertility. Spermatocytes of cKO mice showed failure to complete prophase I of meiosis with arrest at the midpachytene stage. Staining of synaptonemal complex protein 3 and γH2AX, markers of the meiotic synaptonemal complex and DNA damage, respectively, and super illumination microscopy revealed nonhomologous pairing and synapsis defects. Quantitative RT-PCR showed reduction in the expression of genes critical for prophase I of meiosis, including Spo11 (initiator of meiotic double-stranded breaks), Rec8 (meiotic recombination protein), and Rad21L (RAD21-like, cohesin complex component), as well as those involved in the retinoic acid pathway critical for entry into meiosis. RNA-Seq showed 1036 upregulated and 1638 downregulated genes (false discovery rate <0.05) in the Tardbp cKO testis, impacting meiosis pathways. Our work reveals a crucial role for TDP-43 in male meiosis and suggests that some forms of meiotic arrest seen in infertile men may result from the loss of function of TDP-43.

Rotation characteristics and neo-commissural alignment of transcatheter heart valve in type-0 bicuspid aortic valve.

AIMS: This study sought to characterize the rotation of the transcatheter heart valve (THV) and evaluate the neo-commissures overlap with coronary arteries in type-0 bicuspid aortic valve (BAV). METHODS AND RESULTS: This was a single-center, 10-patient, retrospective observational cohort. Pre-TAVI computed tomography and procedural fluoroscopy were analyzed. Coplanar fluoroscopic views were coregistered to pre-TAVI computed tomography to characterize THV rotation and determine coronary overlap. The incidence of severe coronary artery overlap with one coronary artery was 90%. According to our prediction line, type-0 BAV has predicted a higher incidence of overlap with one coronary artery, but lower incidence with both coronary arteries compared to the tricuspid aortic valve (TAV). The rotational angles in two different phases were 3.8 ± 3.2° versus 11.8 ± 8.0° (p = .01) in patients with mixed cusp fusion. Commissural angles in final and initial deployment were 9.6 ± 6.6 versus 18.1 ± 11.0° (p = .021). Applying hypothetic "commissure-middle view" in 0°, ±5°, and ±10°, the incidence of overlap with one coronary artery are 20%, 40%, and 90% separately. CONCLUSIONS: The THV rotation existed and was activated in the last 1/3 deploying phase. With the observed tendency of "automatic commissural alignment," applying the "commissure-middle" view in type-0 BAV may optimize valve alignment and avoid coronary artery overlap.

Prenatal exposure to di-(2-ethylhexyl) phthalate and high-fat diet synergistically disrupts mouse fetal oogenesis and affects folliculogenesis†.

Di-(2-ethylhexyl) phthalate (DEHP) is a chemical that is widely used as a plasticizer. Exposure to DEHP has been shown to alter ovarian function in humans. Additionally, foods high in fat content, regularly found in the western diet, have been shown to be another potential disruptor of fetal ovarian function. Due to DEHP's lipophilicity, high-fat foods can be easily contaminated. Therefore, exposure to DEHP and a high-fat diet are both health concerns, especially in pregnant women, and the effects of these exposures on fetal oocyte quality and quantity should be elucidated. In this study, our goal was to determine if there are synergistic effects of DEHP exposure at an environmentally relevant level (20 µg/kg body weight/day) and high-fat diet on oogenesis and folliculogenesis. Dams were fed with a high-fat diet (45 kcal% fat) or a control diet (10 kcal% fat) 1 week before mating and during pregnancy and lactation. The pregnant mice were dosed with DEHP (20 µg/kg body weight/day) or vehicle control from E10.5 to litter birth. We found that treatment with an environmentally relevant dosage of DEHP and consumption of high-fat diet significantly increases synapsis defects in meiosis and affects folliculogenesis in the F1 generation.

The risk of stanford type-A aortic dissection with different tear size and location: a numerical study.

BACKGROUND: This study is to investigate the influence of hemodynamics on Stanford type-A aortic dissection with different tear size and location, to provide some support for the relationships between the risks (rupture, reverse tearing and further tearing) and tear size and location for clinical treatment. METHODS: Four numerical models of Stanford type-A aortic dissection were established, with different size and location of the tears. The ratio of the area between the entry and re-entry tears(RA) is various within the model; while, the size and the location of the re-entry in the distal descending aorta are fixed. In model A11 and A21, the entry tears are located near the ascending aorta. The RA in these models are 1 and 2, respectively; In the model B11 and B21, the entry tears are located near the proximal descending aorta and the RA in these models are again assigned to 1 and 2, respectively. Then hemodynamics in these models was solved with numerically and the flow patterns and loading distributions were investigated. RESULTS: The flow velocity of the true lumen in model A21, B21 is lower than that in A11, B11, respectively; the time-averaged wall shear stress (TAWSS) of the false lumen in model A21 and B21 is higher, and for ascending aorta false lumen, A11, A21 are higher than B11, B21, respectively. False lumen intimal wall pressure of A11, A21 are always higher than the true lumen ones. CONCLUSION: The variation of the RA can significantly affect the dynamics of blood within the aortic dissection. When the entry tear size is larger than the re-entry tear ones, the false lumen, proximal descending aorta and the wall near re-entry tear are prone to cracking. Entry tear location can significantly alter the hemodynamics of aortic dissection as well. When entry tear location is closer to proximal ascending aorta, false lumen continues to expand and compress the true lumen resulting in the true lumen reduction. For proximal ascending aorta, high pressure in false lumen predicts a higher risk of reverse tear.

Interplay between synaptonemal complex, homologous recombination, and centromeres during mammalian meiosis.

The intimate synapsis of homologous chromosome pairs (homologs) by synaptonemal complexes (SCs) is an essential feature of meiosis. In many organisms, synapsis and homologous recombination are interdependent: recombination promotes SC formation and SCs are required for crossing-over. Moreover, several studies indicate that initiation of SC assembly occurs at sites where crossovers will subsequently form. However, recent analyses in budding yeast and fruit fly imply a special role for centromeres in the initiation of SC formation. In addition, in budding yeast, persistent SC-dependent centromere-association facilitates the disjunction of chromosomes that have failed to become connected by crossovers. Here, we examine the interplay between SCs, recombination, and centromeres in a mammal. In mouse spermatocytes, centromeres do not serve as SC initiation sites and are invariably the last regions to synapse. However, centromeres are refractory to de-synapsis during diplonema and remain associated by short SC fragments. Since SC-dependent centromere association is lost before diakinesis, a direct role in homolog segregation seems unlikely. However, post-SC disassembly, we find evidence of inter-centromeric connections that could play a more direct role in promoting homolog biorientation and disjunction. A second class of persistent SC fragments is shown to be crossover-dependent. Super-resolution structured-illumination microscopy (SIM) reveals that these structures initially connect separate homolog axes and progressively diminish as chiasmata form. Thus, DNA crossing-over (which occurs during pachynema) and axis remodeling appear to be temporally distinct aspects of chiasma formation. SIM analysis of the synapsis and crossover-defective mutant Sycp1⁻/⁻ implies that SCs prevent unregulated fusion of homolog axes. We propose that SC fragments retained during diplonema stabilize nascent bivalents and help orchestrate local chromosome reorganization that promotes centromere and chiasma function.

Functional evaluation of BRCA2 variants mapping to the PALB2-binding and C-terminal DNA-binding domains using a mouse ES cell-based assay.

Single-nucleotide substitutions and small in-frame insertions or deletions identified in human breast cancer susceptibility genes BRCA1 and BRCA2 are frequently classified as variants of unknown clinical significance (VUS) due to the availability of very limited information about their functional consequences. Such variants can most reliably be classified as pathogenic or non-pathogenic based on the data of their co-segregation with breast cancer in affected families and/or their co-occurrence with a pathogenic mutation. Biological assays that examine the effect of variants on protein function can provide important information that can be used in conjunction with available familial data to determine the pathogenicity of VUS. In this report, we have used a previously described mouse embryonic stem (mES) cell-based functional assay to characterize eight BRCA2 VUS that affect highly conserved amino acid residues and map to the N-terminal PALB2-binding or the C-terminal DNA-binding domains. For several of these variants, very limited co-segregation information is available, making it difficult to determine their pathogenicity. Based on their ability to rescue the lethality of Brca2-deficient mES cells and their effect on sensitivity to DNA-damaging agents, homologous recombination and genomic integrity, we have classified these variants as pathogenic or non-pathogenic. In addition, we have used homology-based modeling as a predictive tool to assess the effect of some of these variants on the structural integrity of the C-terminal DNA-binding domain and also generated a knock-in mouse model to analyze the physiological significance of a residue reported to be essential for the interaction of BRCA2 with meiosis-specific recombinase, DMC1.

Exposure to TCBPA stimulates the growth of arterial smooth muscle cells through the activation of the ROS/NF-κB/NLRP3 signaling pathway.

Tetrachlorobisphenol A (TCBPA) and Tetrabromobisphenol S (TBBPS) are organic compounds widely used in industrial production, including in plastic and textile manufacturing. Presently, residual TCBPA is commonly detected in the environment as well as in human and animal sera. Therefore, it is imperative to assess the potential toxicological effects of TCBPA on organismal health. A series of biochemical experiments, including indirect immunofluorescence, ELISA, Western blot, MTT, etc, were conducted to analyze the effects of TCBPA on vascular smooth muscle cells. In this study, the biological impact of TCBPA on arterial smooth muscle cells (ASMCs) was investigated. CCK8 and EdU assays demonstrated significant proliferation of ASMCs following TCBPA treatment. Furthermore, TCBPA induced an inflammatory response in smooth muscle cells, as evidenced by the upregulated expression of inflammatory cytokines including IL-6, IL-1ß, and MCP1. Additionally, we observed that TCBPA triggered an oxidative stress response in ASMCs by measuring ROS levels. To elucidate the underlying molecular mechanism of TCBPA-induced ASMC proliferation, we found that NLRP3 was essential for this process. Further investigation revealed that NLRP3 activation was mediated by NF-κB (which was activated by ROS). In summary, our findings suggest that TCBPA promotes the proliferation of ASMCs through the ROS/NF-κB/NLRP3 signaling cascade. This work indicates that TCBPA may represent a potential risk factor for the development of atherosclerosis, highlighting the need for judicious control of TCBPA usage.

Cell-cycle and Age-Related Modulations in Mouse Chromosome Stiffness.

The intricate structure of chromosomes is complex, and many aspects of chromosome configuration/organization remain to be fully understood. Measuring chromosome stiffness can provide valuable insights into their structure. However, the nature of chromosome stiffness, whether static or dynamic, remains elusive. In this study, we analyzed chromosome stiffness in MI and MII oocytes. We revealed that MI oocytes had a ten-fold increase in stiffness compared to mitotic chromosomes, whereas chromosome stiffness in MII oocytes was relatively low chromosome. We then investigated the contribution of meiosis-specific cohesin complexes to chromosome stiffness in MI and MII oocytes. Surprisingly, the Young's modulus of chromosomes from the three meiosis-specific cohesin mutants did not exhibit significant differences compared to the wild type, indicating that these proteins may not play a substantial role in determining chromosome stiffness. Additionally, our findings revealed an age-related increase in chromosome stiffness in MI oocytes. Age correlates with elevated DNA damage levels, so we investigated the impact of etoposide-induced DNA damage on chromosome stiffness, discovering a reduction in stiffness in response to such damage in MI oocytes. Overall, our study underscores the dynamic nature of chromosome stiffness, subject to changes influenced by the cell cycle and age.

Dzip1 is dynamically expressed in the vertebrate germline and regulates the development of Xenopus primordial germ cells.

Primordial germ cells (PGCs) are the precursors of sperms and oocytes. Proper development of PGCs is crucial for the survival of the species. In many organisms, factors responsible for PGC development are synthesized during early oogenesis and assembled into the germ plasm. During early embryonic development, germ plasm is inherited by a few cells, leading to the formation of PGCs. While germline development has been extensively studied, how components of the germ plasm regulate PGC development is not fully understood. Here, we report that Dzip1 is dynamically expressed in vertebrate germline and is a novel component of the germ plasm in Xenopus and zebrafish. Knockdown of Dzip1 impairs PGC development in Xenopus embryos. At the molecular level, Dzip1 physically interacts with Dazl, an evolutionarily conserved RNA-binding protein that plays a multifaced role during germline development. We further showed that the sequence between amino acid residues 282 and 550 of Dzip1 is responsible for binding to Dazl. Disruption of the binding between Dzip1 and Dazl leads to defective PGC development. Taken together, our results presented here demonstrate that Dzip1 is dynamically expressed in the vertebrate germline and plays a novel function during Xenopus PGC development.

Impact on early outcome after endovascular repair of type B dissection without proximal landing zone using Castor single-branched stent graft-a retrospective cohort study.

Background: The early safety and efficacy of Castor branch stents have been demonstrated. However, the effect of aortic arch morphology on endovascular therapy remains an unresolved issue. This study aims to assess the impact of aortic arch morphology on the early outcomes of endovascular repair using Castor stent graft in patients who have acute type B aortic dissection involving the left subclavian artery (LSA). Methods: This is a retrospective cohort study. From January 2019 to December 2021, forty-one patients scheduled for thoracic endovascular aortic repair (TEVAR) of TBADs from Beijing Anzhen Hospital were enrolled in this retrospective cohort study and divided into two groups based on the length of the proximal landing zone left common carotid artery-LSA (PLZ LCCA-LSA), specifically the distance between the LCCA and the LSA (group A ≤10 mm and group B >10 mm). The study recorded technical success, mortality and aortic-related post-operative adverse events. Morphological indices were analyzed including the bird-beak configuration. The bird-beak configuration refers to the wedge-shaped gap between the undersurface of the endograft and the lesser curvature of the arch. The relationship between the risk of bird-beak configuration and PLZ was assessed with logistic regression analysis. Meanwhile, the relationship between the risk of aortic-related adverse events and bird-beak configuration was assessed with logistic regression analysis. Follow-up data were analyzed by Kaplan-Meier life table analysis. Results: The study included 41 patients with a mean age of 63.1±9.2 years, of which 80.5% were male. 18 patients from group A and 23 patients from group B were included in the comparative analysis. There were no significant differences in aortic-related adverse events, bird-beak phenomenon and re-intervention between groups A and B in 30-day outcomes. Six-month outcomes: aortic-related adverse events and the bird-beak phenomenon were observed in 11 (26.8%) and 12 (29.3%) patients, respectively. There was a significant difference in the occurrence of aortic-related adverse events (P=0.036) and bird-beak phenomenon (P=0.002) between groups A and B. In comparison to group B, the aortic-related adverse event rate was significantly higher in group A, with event-free rates of 83.3%, 83.3%, and 72.2% at 1, 3, and 6 months, respectively (P=0.020). Multivariable logistic regression analyses revealed that PLZ LCCA-LSA length [odds ratio (OR) 0.79; 95% CI: 0.64 to 0.97; P=0.026] was significantly associated with the occurrence of the bird-beak configuration, and bird-beak (OR 17.19; 95% CI: 2.24 to 131.81; P=0.006) was a significant risk factor for aortic-related adverse events. Conclusions: TEVAR with LSA revascularization has good early outcomes. However, it is more susceptible to aortic adverse events when the PLZ LCCA-LSA is less than 10 mm in length. This should be carefully considered, taking into account the risks and benefits.

PTBP1 mediates Sertoli cell actin cytoskeleton organization by regulating alternative splicing of actin regulators.

Spermatogenesis is a biological process within the testis that produces haploid spermatozoa for the continuity of species. Sertoli cells are somatic cells in the seminiferous epithelium that orchestrate spermatogenesis. Cyclic reorganization of Sertoli cell actin cytoskeleton is vital for spermatogenesis, but the underlying mechanism remains largely unclear. Here, we report that RNA-binding protein PTBP1 controls Sertoli cell actin cytoskeleton reorganization by programming alternative splicing of actin cytoskeleton regulators. This splicing control enables ectoplasmic specializations, the actin-based adhesion junctions, to maintain the blood-testis barrier and support spermatid transport and transformation. Particularly, we show that PTBP1 promotes actin bundle formation by repressing the inclusion of exon 14 of Tnik, a kinase present at the ectoplasmic specialization. Our results thus reveal a novel mechanism wherein Sertoli cell actin cytoskeleton dynamics is controlled post-transcriptionally by utilizing functionally distinct isoforms of actin regulatory proteins, and PTBP1 is a critical regulatory factor in generating such isoforms.

RNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis.

Male germ cell development requires precise regulation of gene activity in a cell-type and stage-specific manner, with perturbations in gene expression during spermatogenesis associated with infertility. Here, we use steady-state, nascent and single-cell RNA sequencing strategies to comprehensively characterize gene expression across male germ cell populations, to dissect the mechanisms of gene control and provide new insights towards therapy. We discover a requirement for pausing of RNA Polymerase II (Pol II) at the earliest stages of sperm differentiation to establish the landscape of gene activity across development. Accordingly, genetic knockout of the Pol II pause-inducing factor NELF in immature germ cells blocks differentiation to spermatids. Further, we uncover unanticipated roles for Pol II pausing in the regulation of meiosis during spermatogenesis, with the presence of paused Pol II associated with double-strand break (DSB) formation, and disruption of meiotic gene expression and DSB repair in germ cells lacking NELF.

Altered distribution of MLH1 foci is associated with changes in cohesins and chromosome axis compaction in an asynaptic mutant of tomato.

In most multicellular eukaryotes, synapsis [synaptonemal complex (SC) formation] between pairs of homologous chromosomes during prophase I of meiosis is closely linked with crossing over. Asynaptic mutants in plants have reduced synapsis and increased univalent frequency, often resulting in genetically unbalanced gametes and reduced fertility. Surprisingly, some asynaptic mutants (like as1 in tomato) have wild-type or increased levels of crossing over. To investigate, we examined SC spreads from as1/as1 microsporocytes using both light and electron microscopic immunolocalization. We observed increased numbers of MLH1 foci (a crossover marker) per unit length of SC in as1 mutants compared to wild-type. These changes are associated with reduced levels of detectable cohesin proteins in the axial and lateral elements (AE/LEs) of SCs, and the AE/LEs of as1 mutants are also significantly longer than those of wild-type or another asynaptic mutant. These results indicate that chromosome axis structure, synapsis, and crossover control are all closely linked in plants.

Metformin use is associated with reduced acute kidney injury following coronary artery bypass grafting in patients with type 2 diabetes: An inverse probability of treatment weighting analysis.

STUDY OBJECTIVE: Acute kidney injury (AKI) is a common and serious complication after coronary artery bypass grafting (CABG) surgery. Patients with diabetes are commonly associated with renal microvascular complications and have a greater risk of AKI after CABG surgery. This study aimed to explore whether preoperative metformin administration could reduce the incidence of postoperative AKI following CABG in patients with type 2 diabetes. DESIGN: Patients with diabetes who underwent CABG were retrospectively included in this study. AKI after CABG was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The effects of metformin on postoperative AKI following CABG in patients were compared and analyzed. DATA SOURCE: Patients were enrolled in this study between January 2019 and December 2020 in Beijing Anzhen Hospital. PATIENTS: A total of 812 patients were enrolled. The patients were divided into the metformin group (203 cases) and the control group (609 cases) according to whether metformin was used preoperatively. INTERVENTION: Inverse probability of treatment weighting (IPTW) was applied to minimize baseline differences between the two groups. IPT-weighted p values were analyzed to evaluate the postoperative outcomes between the two groups. MEASUREMENTS AND MAIN RESULTS: The incidence of AKI in the metformin group and the control group was compared. After IPTW adjustment, the incidence of AKI in the metformin group was lower than the control group (IPTW-adjusted p < 0.001). In the subgroup analysis, metformin showed significant protective effects in the estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m2 and eGFR 60-90 mL/min per 1.73 m2 subgroups, which was not observed in the eGFR ≥90 mL/min per 1.73 m2 subgroup. No significant differences in the incidence of renal replacement therapy, reoperation due to bleeding, in-hospital mortality, or red blood cell transfusion volume were observed between the two groups. CONCLUSIONS: In this study, we provided evidence that preoperative metformin was associated with a significant reduction of postoperative AKI following CABG in patients with diabetes. Metformin showed significant protective effects in patients with mild-to-moderate renal insufficiency.

Simultaneous surgical treatment of aortic coarctation and aortic root disease: a report of case series.

Background: Aortic coarctation (CoA) is a common congenital aortic disease, which is often accompanied by aortic root disease. This study aimed to explore the simultaneous surgical treatment of aortic root replacement and ascending-abdominal aortic bypass grafting for patients with CoA and aortic root disease. Case Description: From June 2014 to December 2019, nine patients with CoA and aortic root disease underwent simultaneous surgical treatment involving ascending-abdominal aortic bypass grafting and aortic root replacement (Bentall operation in eight patients and Wheat's operation in one patient). The degree of constriction, cardiopulmonary bypass time, ascending aorta occlusion time, operation time, artificial vessel diameter, ventilator support time and blood loss were recorded and analyzed. The blood pressure data of the limbs were measured pre- and postoperatively. All patients were followed up for 24±7 months. The mean extracorporeal circulation time was 130±17 minutes. The mean duration of the aortic clamp occlusion was 85±14 minutes. The mean operation time was 6.2±1.9 hours. The mean blood loss during and after surgery was 1,958±849 mL. The mean ventilator support time after operation was 20.3±11.6 hours. There were no operative mortalities. The arterial pressure gradient in the upper and lower limbs significantly improved. Postoperative computer-enhanced transvenous angiograms showed that the grafts were open with fluent flow. None of the patients experienced gastrointestinal complications, and no adverse events were observed during the follow-up. Conclusions: Simultaneous surgical treatment with ascending-to-abdominal aorta bypass grafting and aortic root replacement is feasible for patients with CoA and aortic root disease.

Prediction of acute kidney injury following coronary artery bypass graft surgery in elderly Chinese population.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication following coronary artery bypass graft (CABG) surgery. Advanced age is an independent risk factor for the development of AKI, and the incidence of AKI in the elderly increases more rapidly than that in younger patients. This study aimed to develop and validate the risk prediction model for AKI after CABG in elderly patients. METHODS: Patients were retrospectively recruited from January 2019 to December 2020. AKI after CABG was defined according to the criteria of Kidney Disease Improving Global Outcomes (KDIGO). The entire population was divided into the derivation set and the verification set using random split sampling (ratio: 7:3). Lasso regression method was applied to screen for the variables in the derivation set. Decision curve analysis (DCA) and receiver operating characteristic (ROC) curves were plotted to analyze the predictive ability of the model for AKI risk in the derivation set and the verification set. RESULTS: A total of 2155 patients were enrolled in this study. They were randomly divided into the derivation set (1509 cases) and the validation set (646 cases). Risk factors associated with AKI were selected by Lasso regression including T2DM, diabetes mellitus type intraoperative use of intra-aortic ballon pump (IABP), cardiopulmonary bypass (CPB), epinephrine, isoprenaline, and so on. The model was established by Lasso logistic regression. The area under the ROC curve (AUC) of the model for the derivation set was 0.754 (95% CI: 0.720 - 0.789), and that for the validation cohort was 0.718 (95% CI: 0.665 - 0.771). CONCLUSION: In this study, the model with significant preoperative and intraoperative variables showed good prediction performance for AKI following CABG in elderly patients to optimize postoperative treatment strategies and improve early prognosis.