ISGylation of NF-κBp65 by SCFFBXL19 E3 Ligase Diminishes Endothelial Inflammation.

BACKGROUND: NF-κB (nuclear factor kappa B) plays a pivotal role in endothelial cell (EC) inflammation. Protein ISGylation is regulated by E3 ISG15 (interferon-stimulated gene 15) ligases; however, ISGylation of NF-κBp65 and its role in EC functions have not been investigated. Here, we investigate whether p65 is ISGylated and the role of its ISGylation in endothelial functions. METHODS: In vitro ISGylation assay and EC inflammation were performed. EC-specific transgenic mice were utilized in a murine model of acute lung injury. RESULTS: We find that NF-κBp65 is ISGylated in resting ECs and that the posttranslational modification is reversible. TNFα (tumor necrosis factor alpha) and endotoxin stimulation of EC reduce p65 ISGylation, promoting its serine phosphorylation through reducing its association with a phosphatase WIP1 (wild-type p53-induced phosphatase 1). Mechanistically, an SCF (Skp1-Cul1-F-box) protein E3 ligase SCFFBXL19 is identified as a new ISG15 E3 ligase that targets and catalyzes ISGylation of p65. Depletion of FBXL19 (F-box and leucine-rich repeat protein 19) increases p65 phosphorylation and EC inflammation, suggesting a negative correlation between p65 ISGylation and phosphorylation. Moreover, EC-specific FBXL19 overexpressing humanized transgenic mice exhibit reduced lung inflammation and severity of experimental acute lung injury. CONCLUSIONS: Together, our data reveal a new posttranslational modification of p65 catalyzed by a previously unrecognized role of SCFFBXL19 as an ISG15 E3 ligase that modulates EC inflammation.

Bridge pacemaker with an externalized active fixation lead for pacemaker-dependent patients with device infection.

BACKGROUND: The risk of Cardiac Implantable Electronic Device (CIED) infection has been increasing in recent years. For pacemaker-dependent patients, a temporary pacemaker is needed before a new device can be implanted. The aim of this study is to evaluate the safety and efficacy of using a temporary pacing device with an externalized active fixation lead (bridge pacemaker) before a new device can be implanted in pacemaker-dependent patients with device infection. METHODS: All patients who were admitted to our cardiac center with CIED infection and in need of bridge pacemaker implantation from April 2013 to August 2020 were prospectively enrolled in this observational study. The medical records of all patients were collected and evaluated. All procedure-related complications were also collected. Long-term outcomes, including reinfection and death within 1 year after hospital discharge, were collected through telephone follow-ups. RESULTS: During the study period, 1050 patients underwent CIED extraction, of which 312 pacemaker-dependent patients underwent bridge pacemaker implantation. The mean age of the extracted leads was 44 ± 38.7 months. The bridge pacemakers were in use for a mean duration of 6 days. Nine patients developed procedure-related complications including pericardial tamponade, pneumothorax, peripheral venous thrombosis, and pulmonary embolism. Three patients developed complications that were related to their bridge pacemakers, including lead dislodgement, over-sensing and elevated pacing threshold. During the 1-year follow-up, it was found that four patients had developed CIED reinfection and three patients had died due to cardiac-related reasons. CONCLUSIONS: A bridge pacemaker with an externalized active fixation lead is safe and efficacious for pacemaker-dependent patients with device infection.

Transfemoral extraction of pacemaker and implantable cardioverter defibrillator leads using Needle's Eye Snare: a single-center experience of more than 900 leads.

The femoral approach with the Needle's Eye Snare (NES) is often used for bailout after failure of the superior approach for transvenous lead extraction (TLE). The safety and efficacy of the NES as a first-line tool for TLE remain unclear. The medical records of patients who underwent TLE via the femoral approach utilizing the NES from May 2014 to June 2019 in Peking University People's Hospital were retrospectively reviewed. Nine hundred and eighty-five leads were extracted in 492 patients (369 men; mean age 72.8 ± 29.0 years). The median (range) number of leads extracted per patient was 2 (1-6). The mean indwelling time of all extracted leads was 112.6 ± 52.0 months. The complete procedure success rate, clinical success rate, and failure rate were 94.1% (463/492), 97.8% (481/492), and 1.1% (11/492), respectively. Major complications including death occurred in nine patients (1.9%), of whom eight developed cardiac tamponade. Among these eight patients, emergency pericardiocentesis followed by rescue surgical repair if necessary was successful in 6 (75.0%) and failed in 2 (25.0%). No significant differences were found in the clinical success rate or major complications rate between patients with pacemakers and implantable cardioverter defibrillators, or between patients with infected and uninfected leads. A femoral approach with the NES is safe and effective for TLE of both pacing and defibrillator leads and could be considered a first-line approach. Cardiac tamponade was the most frequent cardiovascular complication. A strategy of emergency pericardiocentesis followed by a rescue surgical approach seems to be reasonable technique to treat a cardiac tamponade.

Quercetin reduces tendon adhesion in rat through suppression of oxidative stress.

BACKGROUND: Tendon adhesion is one of the most common clinical problems, which poses a considerable challenge to orthopedics doctors. Quercetin (QUE) as a popular drug at present, it has various biological functions, including anti-inflammatory, anti-ischemic, anti-peroxidation, and antioxidant. The purpose of this study was to investigate the effect of quercetin on tendon adhesion and whether quercetin can inhibit oxidative stress. METHOD: Thirty-six rats were randomly divided into three groups, including control group, low QUE (50 mg/kg/day) group, and high QUE (100 mg/kg/day) group. After 1 week, the levels of SOD, MDA and GPx were measured. The degree of tendon adhesion was assessed by macroscopic evaluation and histological evaluation. After 4 weeks. Besides, the pharmacological toxicity of quercetin to main organs were evaluated by histological analysis. RESULTS: The extent of superoxide dismutase (SOD) and glutathione peroxidase (GPx) of tendon tissue in high QUE group was significantly higher than those of low QUE group and control group. And the extent of malondialdehyde (MDA) of tendon tissue in high QUE group was significantly lower than that of low QUE group and control group. By macroscopic evaluation and histological analysis, the extent of tendon adhesion in high QUE group was lower than low QUE group and control group. However, there were no significant changes of the major organs through histological analysis. CONCLUSIONS: Quercetin may be a good and safe strategy in preventing tendon adhesion. But further clinical research is needed before its recommendation in the prevention and treatment of tendon adhesion.

UV radiation-induced SUMOylation of DDB2 regulates nucleotide excision repair.

Subunit 2 of DNA damage-binding protein complex (DDB2) is an early sensor of nucleotide excision repair (NER) pathway for eliminating DNA damage induced by UV radiation (UVR) and cisplatin treatments of mammalian cells. DDB2 is modified by ubiquitin and poly(ADP-ribose) (PAR) in response to UVR, and these modifications play a crucial role in regulating NER. Here, using immuno-analysis of irradiated cell extracts, we have identified multiple post-irradiation modifications of DDB2 protein. Interestingly, although the DNA lesions induced by both UVR and cisplatin are corrected by NER, only the UV irradiation, but not the cisplatin treatment, induces any discernable DDB2 modifications. We, for the first time, show that the appearance of UVR-induced DDB2 modifications depend on the binding of DDB2 to the damaged chromatin and the participation of functionally active 26S proteasome. The in vitro and in vivo analysis revealed that SUMO-1 conjugations comprise a significant portion of these UVR-induced DDB2 modifications. Mapping of SUMO-modified sites demonstrated that UVR-induced SUMOylation occurs on Lys-309 residue of DDB2 protein. Mutation of Lys-309 to Arg-309 diminished the DDB2 SUMOylation observable both in vitro and in vivo. Moreover, K309R mutated DDB2 lost its function of recruiting XPC to the DNA damage sites, as well as the ability to repair cyclobutane pyrimidine dimers following cellular UV irradiation. Taken together, our results indicate that DDB2 is modified by SUMOylation upon UV irradiation, and this post-translational modification plays an important role in the initial recognition and processing of UVR-induced DNA damage occurring within the context of chromatin.

Valosin-containing Protein (VCP)/p97 Segregase Mediates Proteolytic Processing of Cockayne Syndrome Group B (CSB) in Damaged Chromatin.

Cockayne syndrome group A and B (CSB) proteins act in transcription-coupled repair, a subpathway of nucleotide excision repair. Here we demonstrate that valosin-containing protein (VCP)/p97 segregase functions in ultraviolet radiation (UVR)-induced ubiquitin-mediated CSB degradation. We show that VCP/p97 inhibition and siRNA-mediated ablation of VCP/p97 and its cofactors UFD1 and UBXD7 impair CSB degradation. VCP/p97 inhibition also results in the accumulation of CSB in chromatin. Moreover, VCP/p97 interacts with both native and ubiquitin-conjugated forms of CSB. The localized cellular UVR exposures lead to VCP/p97 accumulation at DNA damage spots, forming distinct UVR-induced foci. However, manifestation of VCP/p97 foci is independent of CSB and UBXD7. Furthermore, VCP/p97 and UBXD7 associate with the Cockayne syndrome group A-DDB1-Cul4A complex, an E3 ligase responsible for CSB ubiquitination. Compromising proteasome and VCP/p97 function allows accumulation of both native and ubiquitinated CSB and results in an increase of UBXD7, proteasomal RPN2, and Sug1 in the chromatin compartment. Surprisingly, both biochemical inhibition and genetic defect of VCP/p97 enhance the recovery of RNA synthesis following UVR, whereas both VCP/p97 and proteasome inhibitions decrease cell viability. Our findings reveal a new role of VCP/p97 segregase in the timely processing of ubiquitinated CSB from damaged chromatin.

DDB2 modulates TGF-ß signal transduction in human ovarian cancer cells by downregulating NEDD4L.

The expression of DNA damage-binding protein 2 (DDB2) has been linked to the prognosis of ovarian cancer and its underlying transcription regulatory function was proposed to contribute to the favorable treatment outcome. By applying gene microarray analysis, we discovered neural precursor cell expressed, developmentally downregulated 4-Like (NEDD4L) as a previously unidentified downstream gene regulated by DDB2. Mechanistic investigation demonstrated that DDB2 can bind to the promoter region of NEDD4L and recruit enhancer of zeste homolog 2 histone methyltransferase to repress NEDD4L transcription by enhancing histone H3 lysine 27 trimethylation (H3K27me3) at the NEDD4L promoter. Given that NEDD4L plays an important role in constraining transforming growth factor ß signaling by targeting activated Smad2/Smad3 for degradation, we investigated the role of DDB2 in the regulation of TGF-ß signaling in ovarian cancer cells. Our data indicate that DDB2 enhances TGF-ß signal transduction and increases the responsiveness of ovarian cancer cells to TGF-ß-induced growth inhibition. The study has uncovered an unappreciated regulatory mode that hinges on the interaction between DDB2 and NEDD4L in human ovarian cancer cells. The novel mechanism proposes the DDB2-mediated fine-tuning of TGF-ß signaling and its downstream effects that impinge upon tumor growth in ovarian cancers.

A systematic review of suture-button versus syndesmotic screw in the treatment of distal tibiofibular syndesmosis injury.

BACKGROUND: Now, using a suture-button device to treat distal tibiofibular syndesmotic injuries is overwhelming due to its advantages over screw fixation. Current systematic review was conducted to make a comparison between suture-button fixation and traditionally screw fixation in the treatment of syndesmotic injuries. The outcomes included functional outcomes, implant removal, implant failure, malreduction, post-operative complications (except implant failure and malreduction), and cost-effectiveness aspects. METHOD: A literature search in the electronic databases of Medline, Embase, the Cochrane Library, Web of Science was conducted to identify studies until March 2017. The references of the included articles were also checked for potentially relevant studies. Only English articles were included. We followed the Preferred Reporting Items for Systematics reviews and Meta-Analysis (PRISMA) guidelines in this review. RESULTS: Finally, 10 studies were identified, encompassing a total of 390 patients. The mean American Orthopaedic Foot and Ankle Society ankle score (AOFAS) score of 150 patients treated with the suture-button device was 91.06 points, with an average follow-up of 17.58 months, and the mean AOFAS score of 150 patients treated with syndesmotic screws was 87.78 points, with an average follow-up of 17.73 months. Implant removal was reported in 5 of 134 (3.7%) patients treated with the suture-button device, and in 54 of 134 (40.2%) patients treated with the syndesmotic screw. No patient in the suture-button fixation group had implant failure, however the rate of implant failure in the screw fixation group was 30.9%. Malreduction was reported in 1 of 93 (1.0%) patients treated with the suture-button device, and in 12 of 95 (12.6%) patients treated with the syndesmotic screw. The rate of post-operative complications in the suture-button fixation group was 12.0% and 16.4% in the screw fixation group. There was only one publication demonstrated about cost-effectiveness aspects, it showed that patients treated with the suture-button device spent on average $1482 less and had a higher quality of life by 0.058 quality-adjusted life-year compared with patients who received fixation with 2 syndesmotic screws in supination-external rotation type 4 injuries. CONCLUSION: Based on our research, though the suture-button fixation group had similar functional outcome (measured on the AOFAS score) and post-operative complication rate compared with the syndesmotic screw fixation group, the suture-button device could lead to better objective range of motion (ROM) measurements and earlier return to work. Besides, the suture-button fixation group had lower rate of implant removal, implant failure, and malreduction. However, high-quality randomized controlled trials with more uniformity in outcome reporting are desirable to determine the long-term effects and cost-effectiveness of the suture-button device.

Combined application versus topical and intravenous application of tranexamic acid following primary total hip arthroplasty: a meta-analysis.

BACKGROUND: The use of intravenous (IV) or topical tranexamic acid (TXA) in total hip arthroplasty has been proven to be effective and safe in total hip arthroplasty. However, which of these two administration routes is better has not been determined. The combined administration of TXA has been used in total knee arthroplasty with satisfactory results. We hypothesized that combined application of TXA may be the most effective way without increased rate of thrombotic events such as deep vein thrombosis (DVT) and pulmonary embolisms (PE) in patients subjected to primary total hip replacement (THA). A meta-analysis was conducted to compare the efficacy and safety of the combined use of tranexamic acid (TXA) relative to topical or intravenous (IV) use alone for treatment of primary THA. The outcomes included total blood loss, postoperative hemoglobin decline, transfusion rates, and the incidence rates of deep vein thrombosis (DVT) and pulmonary embolisms (PE). METHODS: We searched electronic databases including PubMed, EMBASE, the Cochrane Library, Web of Science, the Chinese Biomedical Literature database, the CNKI database, and Wanfang Data until September 2016. The references of the included articles were also checked for additional potentially relevant studies. There were no language restrictions for the search. The data of the included studies were analyzed using RevMan 5.3 software. RESULTS: Seven studies met the inclusion criteria, encompassing a total of 1762 patients. Our meta-analysis demonstrated that total blood loss, postoperative hemoglobin decline, and transfusion rates were significantly lower for patients that received the combined treatment compared to patients that received either topical or intravenous administration of TXA. No statistical differences were found in the incidence of deep venous thrombosis (DVT) or pulmonary embolism (PE). CONCLUSION: The group that received the combined treatment had lower total blood loss, postoperative hemoglobin decline, and transfusion rates without an increased rate of thrombotic events (DVT or PE). The topical or intravenous use of TXA in primary THA is generally considered to be safe and effective. This meta-analysis demonstrated that combined TXA application may be superior to topical or intravenous application of TXA alone. However, larger, high-quality randomized control trials are required for greater confidence in this finding.

Ubiquitin-specific protease 7 regulates nucleotide excision repair through deubiquitinating XPC protein and preventing XPC protein from undergoing ultraviolet light-induced and VCP/p97 protein-regulated proteolysis.

Ubiquitin specific protease 7 (USP7) is a known deubiquitinating enzyme for tumor suppressor p53 and its downstream regulator, E3 ubiquitin ligase Mdm2. Here we report that USP7 regulates nucleotide excision repair (NER) via deubiquitinating xeroderma pigmentosum complementation group C (XPC) protein, a critical damage recognition factor that binds to helix-distorting DNA lesions and initiates NER. XPC is ubiquitinated during the early stage of NER of UV light-induced DNA lesions. We demonstrate that transiently compromising cellular USP7 by siRNA and chemical inhibition leads to accumulation of ubiquitinated forms of XPC, whereas complete USP7 deficiency leads to rapid ubiquitin-mediated XPC degradation upon UV irradiation. We show that USP7 physically interacts with XPC in vitro and in vivo. Overexpression of wild-type USP7, but not its catalytically inactive or interaction-defective mutants, reduces the ubiquitinated forms of XPC. Importantly, USP7 efficiently deubiquitinates XPC-ubiquitin conjugates in deubiquitination assays in vitro. We further show that valosin-containing protein (VCP)/p97 is involved in UV light-induced XPC degradation in USP7-deficient cells. VCP/p97 is readily recruited to DNA damage sites and colocalizes with XPC. Chemical inhibition of the activity of VCP/p97 ATPase causes an increase in ubiquitinated XPC on DNA-damaged chromatin. Moreover, USP7 deficiency severely impairs the repair of cyclobutane pyrimidine dimers and, to a lesser extent, affects the repair of 6-4 photoproducts. Taken together, our findings uncovered an important role of USP7 in regulating NER via deubiquitinating XPC and by preventing its VCP/p97-regulated proteolysis.

Effect of Cooling Rate on the Microstructure and Mechanical Property of Nickel-Based Superalloy MAR-M247.

Heat treatment is an important process for optimizing the microstructures of superalloys, and the cooling rate after solid solution treatment is one of the most critical parameters. In this work, we treated solid solution MAR-M247 alloys with water quenching, air cooling, and furnace cooling. Microstructure characterization, hardness, and room temperature tensile tests were conducted to investigate the effect of cooling rate on the microstructure and mechanical properties of MAR-M247 alloys. The results showed that the cooling rate after solid solution treatment mainly affected the precipitation behavior of the secondary γ' phase, but it had few effects on other microstructure characterizations, including grain size, γ/γ' eutectic, and MC carbide. The water-quenched sample had the highest cooling rate (400 °C/s) and hardness (400 HV) but suffered from premature fracture because of quenching cracks. A further decrease in cooling rate from 1.5 °C/s to 0.1 °C/s deteriorated hardness (384 HV to 364 HV) and yield strength (960 MPa to 771 MPa) but increased elongation (8.5% to 13.5%). Moreover, the deformation mechanism was transformed from dislocation shearing to Orowan bypassing. The decreased yield strength was mainly due to the weakened precipitation strengthening resulting from γ'-phase coarsening. The improved elongation was attributed to not only the higher work-hardening index caused by interface dislocation networks but also the more uniform deformation, which delayed necking.

Parental Psychological Control and Adolescent Academic Achievement: The Mediating Role of Achievement Goal Orientation.

This study examined the multiple mediating roles of achievement goal orientation between three parental psychological control (PPC) strategies and adolescents' academic achievement. The study sample consisted of 2613 Chinese middle school adolescents (52.6% boys) who were followed for one and a half years; they completed questionnaires on PPC (including love withdrawal, guilt induction, and authority assertion), achievement goal orientation (involving the mastery approach, the performance approach, and performance-avoidance goals), and academic achievement. We found that (1) the direct effects of the three strategies on academic performance differed, with love withdrawal directly and negatively predicting adolescents' academic achievement and guilt induction and authority assertion not being significant direct predictors. (2) The mediating role of achievement goal orientations differed across the psychological control strategies. Specifically, love withdrawal led to adolescents' academic achievement through their performance-approach goal orientation, performance-avoidance goal orientation, and mastery goal orientation. Moreover, guilt induction and authority assertion had impacts only on adolescents' performance-approach and performance-avoidance goal orientations. This study highlights the negative impact of love withdrawal on adolescents' internal motivation and academic achievement by warning parents not to use this strategy to influence their children's thoughts and feelings.

Association between Deltoid Muscle Density and Proximal Humeral Fracture in Elderly Patients.

Background: The potential role of deltoid muscle density in the occurrence of proximal humeral fractures remains uncertain. Therefore, the primary objective of this study was to examine the correlation between deltoid muscle density, as measured by CT attenuation value in Hounsfield units (HU), and the incidence of proximal humeral fractures in elderly patients. By investigating this association, we aim to shed light on the possible influence of deltoid muscle density on fracture risk in this specific population. Methods: A total of 68 patients with computed tomography (CT) images were retrospectively reviewed. Among them, 34 patients presented with fractures following low-energy injuries, while the remaining 34 patients served as controls and underwent CT scans after low-energy injuries without any fractures. The muscle density of the deltoid muscles was assessed at the approximate tubercle of humerus. We compared these parameters between the two groups and conducted analyses considering factors such as age, sex, laterality, and deltoid muscle density of the shoulders. Results: The demographic factors related to the shoulder did not exhibit any significant association with proximal humeral fracture. However, we observed a noteworthy difference in deltoid muscle density between patients with fractures (40.85 ± 1.35) and the control group (47.08 ± 1.61) (p = 0.0042), indicating a lower muscle density in the fracture group. Conclusion: Based on the findings of this study, we can conclude that there exists a negative correlation between deltoid muscle density and the incidence of proximal humeral fractures. These results suggest that lower deltoid muscle density may be associated with an increased risk of proximal humeral fractures in the elderly population under investigation.

Suture Bridge Technique with 5-Ethibond: A Promising Approach for Infrapatellar Pole Fracture Treatment.

Purpose: Infrapatellar pole fractures are challenging injuries that require appropriate treatment to ensure optimal functional outcomes. This study aimed to introduce the application of the Suture Bridge technique using the 5-Ethibond for the treatment of infrapatellar patella fracture. Methods: Five cases of infrapatellar pole fracture that were treated at our institution between February 2020 and September 2021. The patients included one male and four females, with an average age of 66 years (range: 60-77 years). All patients were treated with the Suture Bridge technique using the 5-Ethibond to preserve the infrapatellar pole. Results: The average operative time was 64 min (range: 50-80 min). The average blood loss during surgery was 51 mL (range: 40-60 mL). All cases demonstrated fracture healing at an average of 10 weeks (range 8-12) after surgery. The patients were followed up for an average period of 14.8 months (8-22). No wound infection or second displacement of fracture fragment was found. Full range of motion was restored in all patients within 12-14 weeks after surgery. None of the patients complained of anterior knee pain. Conclusions: Based on the findings of the study, it appears that the Suture Bridge technique using 5-Ethibond is a promising and viable option for the treatment of infrapatellar pole fractures.

Oxygen vacancy formation strengthened microwave catalysis of Zn-Zr solid solution for antibiotic-free therapy strategies of bacteria-infected osteomyelitis.

Osteomyelitis, a grave deep tissue infection primarily caused by Staphylococcus aureus, results in serious complications such as abscesses and sepsis. With the incidence from open fractures exceeding 30 % and prevalent antibiotic resistance due to extensive treatment regimens, there's an urgent need for innovative, antibiotic-free strategies. Photothermal therapy (PTT) and photodynamic therapy (PDT) renowned for generating localized reactive oxygen species (ROS), face limitations in penetration depth. To overcome this, our method combines the deep penetration attributes of medical microwaves (MW) with the synergistic effects of the ZnO/ZrO2 solid solution. Comprehensive in vitro and in vivo evaluations showcased the solid-solution's potent antibacterial efficacy and biocompatibility. The ZnO/ZrO2 solid solution, especially in a 7:3 M ratio, manifests superior microstructural characteristics, optimizing MW-assisted therapy. Our findings highlight the potential of this integrated strategy as a promising avenue in osteomyelitis management.

Association analysis between genetic variants of MDM2 gene and osteosarcoma susceptibility in Chinese.

Osteosarcoma (OS) is the most common pediatric bone malignancy worldwide. The MDM2 gene is an important candidate gene for influencing the susceptibility to OS. The objective of this study aimed to detect the potential association between MDM2 genetic variants and OS susceptibility in Chinese Han population. We recruited 415 OS patients and 431 cancer-free controls in this case-control study. The c.44C>T and c.1002T>C genetic variants in MDM2 gene were investigated using created restriction site-polymerase chain reaction (CRS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP), respectively. We found that the genotypes/alleles of c.44C>T and c.1002T>C were statistically associated with the increased risk of OS (for c.44C>T, TT versus (vs.) CC: OR = 2.43, 95% CI 1.49-3.95, p < 0.001; T vs. C: OR = 1.36, 95% CI 1.11-1.67, p = 0.003; for c.1002T>C, CC vs. TT: OR = 2.38, 95% CI 1.37-4.13, p = 0.002; C vs. T: OR = 1.27, 95% CI 1.02-1.56, p = 0.030). The T allele and TT genotype of c.44C>T and C allele and CC genotype of c.1002T>C could be increased risk factors for the susceptibility to OS. Results from this study suggest that MDM2 genetic variants are potentially related to OS susceptibility in Chinese Han population, and might be used as molecular markers for assessing OS susceptibility.

Case report: Unusual cause of refractory hypoxemia after pacemaker lead extraction.

A 59-year-old woman with a history of a pacemaker implanted for III-degree atrioventricular block was admitted due to pocket infection. The atrial and ventricular leads were removed via the right femoral vein using a needle's eye snare. Hypoxemia was observed immediately after the removal of the lead. It was refractory to oxygen therapy. The pulse oxygen saturation (SpO2) showed 89% in the supine position and 77% in the upright position. However, the CTPA and pulmonary perfusion SPECT/CT imaging did not reveal any signs of pulmonary embolism. Pulmonary function tests and chest CT showed normal results. Transthoracic contrast echocardiography revealed a patent foramen ovale (PFO) and a right-to-left intracardiac shunt, no significant tricuspid regurgitation, without any signs of elevated right heart pressure or pulmonary hypertension. Hypoxemia was considered to be associated with the right-to-left shunt through PFO. The condition was relieved by percutaneous closure of the PFO. Refractory hypoxemia resulting from an intracardiac right-to-left shunt following pacemaker lead extraction is a rare but serious complication. Transthoracic contrast echocardiography helps in diagnosis. If the right-to-left intracardiac shunt through PFO persists irreversibly and the associated hypoxemic symptoms are significant, closure of the PFO is necessary. Transesophageal echocardiography also revealed the presence of a left-to-right shunt through PFO during cardiac systole. The closure of the PFO is also necessary to avoid long-term complications, such as chronic pulmonary hypertension and right heart failure.

Predictors for adverse events during cardiac lead extraction - Experience from a large single centre.

BACKGROUND: As the use of cardiac implantable electronic devices (CIED) has increased in recent years, the need for transvenous lead extraction (TLE) has also steadily increased. However, the TLE procedure could lead to serious complications and even death. Clinical decision-making tools are necessary for predicting these adverse events, but the appropriate tools have not yet been developed. OBJECTIVE: To explore the possible predictors and develop a clinical model to predict TLE related adverse events. METHODS: All the patients who were admitted to our cardiac center for TLE from January 2014 to January 2021 were included in this study. The patient information, device baseline characteristics, procedure-related information, complications and outcomes were recorded. Independent predictors of TLE related adverse events were identified by univariate, LASSO and multivariate analysis. A nomogram for predicting these adverse events was developed based on these independent predictors. Calibration and decision curve analysis were conducted to evaluate the nomogram. RESULTS: One thousand and one hundred patients were included in this study, 778 (70.7%) were male and the median age was 68 years old. A total of 2,208 leads were extracted and 2.01±0.74 leads were extracted per procedure. Fifty-five patients (5%) developed adverse events including minor complications (2.4%), major complications (2.3%) and death (0.27%). Seven independent predictors for TLE related adverse events were identified and selected to establish the nomogram including BMI, female gender, hypoalbuminemia, number of extracted leads>3, longest dwell time of the extracted leads and manual traction. The area under the receiver operating characteristic (ROC) curve (AUC) for the prediction model was 0.774. Calibration curve and decision curve analysis showed that the nomogram had good prediction performance. CONCLUSION: TLE related adverse events are some of the key issues that concern clinicians. We have identified seven independent factors and established a predictive model that may help clinicians identify at-risk patients and create better plans for lead extraction.

Effect of Deformation Conditions on Strain-Induced Precipitation of 7Mo Super-Austenitic Stainless Steel.

Strain-induced precipitation (SIP) behaviors of 7Mo super-austenitic stainless steel (SASS) under various deformation conditions were studied by stress relaxation tests. The research demonstrates that sigma phases are the primary SIP phases of 7Mo SASS. Generally, SIP is mainly distributed in granular shape at the boundaries of deformed grains or recrystallized grains, as well as around the deformed microstructure, such as deformation twin layers/matrix interfaces. The variation of deformation parameters can lead to changes in microstructure, therefore influencing the distribution of SIP. For instance, with the temperature increases, the SIP distribution gradually evolves from deformed grain boundaries to recrystallized grain boundaries. The average size of SIP increases with increasing temperature and strain, as well as decreasing strain rate. The SIP content also increases with increasing strain and decreasing strain rate, while exhibiting an initial rise followed by a decline with increasing temperature, reaching its maximum value at 850 °C. The presence of SIP can promote recrystallization by particle-induced nucleation (PSN) mechanism during the hot deformation process. Moreover, the boundaries of these recrystallized grains can also serve as nucleation sites for SIP, therefore promoting SIP. This process can be simplified as SIP→PSNRecrystallization→Nucleation sitesSIP. With the increase in holding time and the consumption of stored energy, the process gradually slows down, leading to the formation of a multi-layer structure, namely SIPs/Recrystallized grains/SIPs structure. Moreover, SIP at recrystallized grain boundaries can hinder the growth of recrystallized grains. Through this study, a comprehensive understanding of the SIP behaviors in 7Mo SASS under different deformation conditions has been achieved, as well as the interaction between SIP and recrystallization. This finding provides valuable insights for effective control or regulation of SIP and optimizing the hot working processes of 7Mo SASS.

USP13 regulates cell senescence through mediating MDM2 stability.

AIMS: Lung aging results in altered lung function, reduced lung remodeling and regenerative capacity, and increased susceptibility to acute and chronic lung diseases. The molecular and physiological underlying mechanisms of lung aging remain unclear. Mounting evidence suggests that deubiquitinating enzymes (DUBs) play a critical role in tissue aging and diseases through regulation of cellular signaling pathways. Here we investigate the role of Ubiquitin-Specific Protease 13 (USP13) in cell senescence and lung aging and its underlying mechanisms. MAIN METHODS: Protein levels of USP13 and MDM2 in lung tissues from aged and young mice were compared. Gene silencing and overexpression of USP13 in human cell lines were performed. MDM2 levels were examined by Quantitative Real-Time PCR and Western blotting analysis. The cell senescence levels of human cells were checked by the ß-galactosidase staining. KEY FINDINGS: Lung tissues from aged mice showed higher levels of USP13 compared to younger mice. We found a negative correlation between USP13 and MDM2 expression in lung tissues of aged mice. The increased protein levels of MDM2 were detected in lung tissues of USP13 deficient mice. Furthermore, overexpression of USP13 promoted cell senescence. Knockdown of USP13 increased MDM2 levels in lung cells, while overexpression of USP13 reduced it. The degradation of MDM2 caused by USP13 was prevented by the proteasome inhibitor MG132. Furthermore, we showed that USP13 targeted and reduced K63-linked polyubiquitination of MDM2. These results demonstrate that USP13 is involved in the aging signaling pathway in lungs through regulation of MDM2.