Risk Prediction Models for Renal Function Decline After Cardiac Surgery Within Different Preoperative Glomerular Filtration Rate Strata.

BACKGROUND: Our goal was to create a simple risk-prediction model for renal function decline after cardiac surgery to help focus renal follow-up efforts on patients most likely to benefit. METHODS AND RESULTS: This single-center retrospective cohort study enrolled 24 904 patients who underwent cardiac surgery from 2012 to 2019 at Fuwai Hospital, Beijing, China. An estimated glomerular filtration rate (eGFR) reduction of ≥30% 3 months after surgery was considered evidence of renal function decline. Relative to patients with eGFR 60 to 89 mL/min per 1.73 m2 (4.5% [531/11733]), those with eGFR ≥90 mL/min per 1.73 m2 (10.9% [1200/11042]) had a higher risk of renal function decline, whereas those with eGFR ≤59 mL/min per 1.73 m2 (5.8% [124/2129]) did not. Each eGFR stratum had a different strongest contributor to renal function decline: increased baseline eGFR levels for patients with eGFR ≥90 mL/min per 1.73 m2, transfusion of any blood type for patients with eGFR 60 to 89 mL/min per 1.73 m2, and no recovery of renal function at discharge for patients with eGFR ≤59 mL/min per 1.73 m2. Different nomograms were established for the different eGFR strata, which yielded a corrected C-index value of 0.752 for eGFR ≥90 mL/min per 1.73 m2, 0.725 for eGFR 60-89 mL/min per 1.73 m2 and 0.791 for eGFR ≤59 mL/min per 1.73 m2. CONCLUSIONS: Predictors of renal function decline over the follow-up showed marked differences across the eGFR strata. The nomograms incorporated a small number of variables that are readily available in the routine cardiac surgical setting and can be used to predict renal function decline in patients stratified by baseline eGFR.

Profound postinduction hypotension precipitated by immune checkpoint inhibitors: a case report.

BACKGROUND: With the increasing use of immune checkpoint inhibitors (ICIs) in cancer therapy, perioperative healthcare professionals need to be vigilant about potential immune-related adverse events (irAEs). We report a case of severe postinduction hypotension in a patient undergoing laparotomy due to suspected intraabdominal bleeding from gastric cancer and Krukenberg tumors, caused by unrecognized hypothyroidism precipitated by ICIs. CASE PRESENTATION: A 65-year-old Chinese female with a history of gastric adenocarcinoma and Krukenberg tumors, previously treated with nivolumab, presented to the emergency room with abdominal pain and hypotension. Despite ruling out other causes, including hypovolemia and anaphylaxis, her hypotension persisted. The patient was found to have severe hypothyroidism, likely an irAE from the use of nivolumab. Thyroxine replacement therapy resolved the hypotension, and the patient recovered uneventfully after surgery. CONCLUSIONS: This case underscores the importance of considering irAEs, such as hypothyroidism, in patients treated with ICIs. Perioperative healthcare providers must remain vigilant for potential complications and promptly recognize and manage irAEs to optimize patient outcomes.

[Diagnosis and treatment of 11 patients with cevical spondylotic amyotrophy].

OBJECTIVE: To explore clinical features, treatment methods and clinical effects of cervical spondylosis with proximal muscular atrophy. METHODS: Eleven patients with proximal-type cervical spondylotic amyotrophy were retrospectively studied from September 2016 to November 2020, including 7 males and 4 females, aged 38 to 68 years old. Clinical symptoms, MRI and neuroelectrophysiological manifestations were analyzed, and patients were treated with conservative treatment or anterior cervical decompression fusion surgery, respectively. The efficacy was evaluated by manual muscle test (MMT) before and after treatment, and patients' satisfaction was followed up at the same time. RESULTS: All patients were followed up for 6 to 19 months. All 11 patients were unilateral, mainly manifested by atrophy of deltoid muscle, supraspinatus muscle and infraspinatus muscle, and may be accompanied by ipsilateral neck and shoulder pain at early stage. MRI showed lesions at C4,5, C5,6 segments were more common. Electrophysiological examination showed the affected muscle was denervated, and amplitude of compound muscle action potential (CMAP) of innervated nerve on the affected side was lower than that on the healthy side. All patients were obtained bone fusion. One patient who were underwent anterior cervical corpectomy and fusion (ACCF) occurred developed contralateral C5 nerve root paralysis after operation, which recovered completely after 10 weeks of symptomatic treatment. At 12 months after operation, the efficacy was evaluated according to MMT, 3 patients were treated conservatively, 2 patients excellent and 1 good;in 8 patients treated by operation, 3 patients were excellent, 4 good, and 1 moderate. CONCLUSION: The incidence of cervical spondylosis with proximal muscular atrophy is low, which is manifested as unilateral proximal muscle atrophy and may be accompanied by ipsilateral neck and shoulder pain in the early stage. Combined with MRI and neuroelectrophysiological examination, misdiagnosis could be reduced. In the early stage of disease, especially in the case of nucleus pulposus protrusion leading to nerve compression, conservative treatment could be taken. When the conservative treatment is ineffective or the pain cannot be tolerated, anterior decompression surgery is recommended, and the overall effect is satisfactory.

Salivary signatures of oral-brain communication in sleep bruxers.

Introduction: Microbiota and their interaction with hosts have been of great interest in brain research in recent years. However, the role of oral microbiota in mental illness and the underlying mechanism of oral-brain communication remains elusive. Sleep bruxism (SB) is an oral parafunctional activity related to the nervous system and is considered a risk factor for harmful clinical consequences and severe systemic conditions. Exploring the connection between oral microbiota and sleep bruxism may deepen our understanding of the complex relationship between oral-brain axis and provide insights for treatment. Methods: In this study, salivary samples were collected from 22 individuals with SB and 21 healthy controls, and metagenomics with metabolomics was performed. Nonparametric Wilcoxon test were applied for the statistical analysis between the two groups. Microbial dysbiosis and altered oral metabolites were found in the SB individuals. Results: The characteristic metabolite N-acetylglucosamine (GlcNAc) (VIP=8.4823, P<0.05) was correlated to a statistically lower Streptococcus mitis level in SB individuals. Salivary IFN-g level and IFN-g/IL-4 ratio were detected with significant changes in a chip assay. Amino acid metabolism pathways were upregulated, and the pathway with the largest number of differentially expressed genes is related to amino-tRNA charging pathway, while the most significantly enriched pathway is related to arginine biosynthesis. Neurotransmitter-associated pathways with glutamatergic and GABAergic synapses and cardiovascular system-related pathways were enriched in the SB group. Discussion: These results indicate a possible neuroimmune regulatory network of oral-brain communication in SB, which helps explain the mechanism of the oral microbiome with the host in sleep bruxers and provides a reference for early clinical and therapeutic intervention to improve the diagnosis and treatment of SB and similar diseases.

Postoperative acute kidney injury after on-pump cardiac surgery in patients with connective tissue disease.

Objective: Patients with connective tissue disease have a poor prognosis after receiving cardiac surgery. This study described the clinical scenarios and investigated factors correlated with acute kidney injury (AKI) after on-pump cardiac surgery in patients with systemic lupus erythematosus (SLE) or vasculitis. Methods: Patients with SLE or vasculitis who underwent on-pump cardiac surgery from March 2002 to March 2022 were enrolled, while patients with preoperative renal dysfunction were excluded. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Uni- and multivariable analyses were performed to identify potential factors associated with postoperative AKI. Results: Among 123 patients enrolled, 39 (31.7%) developed AKI within seven days after receiving on-pump cardiac surgery. Four patients died in the hospital, resulting in an overall in-hospital mortality of 3.3%, and all deaths occurred in the AKI group. Patients in the AKI group also had longer ICU stays (median difference 3.0 day, 95% CI: 1.0-4.0, P < 0.001) and extubation time (median difference 1.0 days, 95% CI: 0-2.0, P < 0.001) than those in the non-AKI group. Multivariable logistic regression revealed that BMI over 24 kg/m2 (OR: 3.00, 95% CI: 1.24-7.28) and comorbid SLE (OR: 4.73, 95% CI: 1.73-12.93) were independently correlated with postoperative AKI. Conclusion: Factors potentially correlated with AKI following on-pump cardiac surgery in patients with connective tissue disease were explored. Clinicians should pay more attention to preoperative evaluation and intraoperative management in patients with risk factors.

Tumor-specific GPX4 degradation enhances ferroptosis-initiated antitumor immune response in mouse models of pancreatic cancer.

Lipid peroxidation-dependent ferroptosis has become an emerging strategy for tumor therapy. However, current strategies not only selectively induce ferroptosis in malignant cells but also trigger ferroptosis in immune cells simultaneously, which can compromise anti-tumor immunity. Here, we used In-Cell Western assays combined with an unbiased drug screening to identify the compound N6F11 as a ferroptosis inducer that triggered the degradation of glutathione peroxidase 4 (GPX4), a key ferroptosis repressor, specifically in cancer cells. N6F11 did not cause the degradation of GPX4 in immune cells, including dendritic, T, natural killer, and neutrophil cells. Mechanistically, N6F11 bound to the RING domain of E3 ubiquitin ligase tripartite motif containing 25 (TRIM25) in cancer cells to trigger TRIM25-mediated K48-linked ubiquitination of GPX4, resulting in its proteasomal degradation. Functionally, N6F11 treatment caused ferroptotic cancer cell death that initiated HMGB1-dependent antitumor immunity mediated by CD8+ T cells. N6F11 also sensitized immune checkpoint blockade that targeted CD274/PD-L1 in advanced cancer models, including genetically engineered mouse models of pancreatic cancer driven by KRAS and TP53 mutations. These findings may establish a safe and efficient strategy to boost ferroptosis-driven antitumor immunity.

Nuclear localization of STING1 competes with canonical signaling to activate AHR for commensal and intestinal homeostasis.

Extensive studies demonstrate the importance of the STING1 (also known as STING) protein as a signaling hub that coordinates immune and autophagic responses to ectopic DNA in the cytoplasm. Here, we report a nuclear function of STING1 in driving the activation of the transcription factor aryl hydrocarbon receptor (AHR) to control gut microbiota composition and homeostasis. This function was independent of DNA sensing and autophagy and showed competitive inhibition with cytoplasmic cyclic guanosine monophosphate (GMP)-AMP synthase (CGAS)-STING1 signaling. Structurally, the cyclic dinucleotide binding domain of STING1 interacted with the AHR N-terminal domain. Proteomic analyses revealed that STING1-mediated transcriptional activation of AHR required additional nuclear partners, including positive and negative regulatory proteins. Although AHR ligands could rescue colitis pathology and dysbiosis in wild-type mice, this protection was abrogated by mutational inactivation of STING1. These findings establish a key framework for understanding the nuclear molecular crosstalk between the microbiota and the immune system.

Diagnosis, Genetics, and Management of 24 Patients With Cardiac Paragangliomas: Experience From a Single Center.

Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation. Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management. Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients. Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99mTc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors. Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease.

A Comparison of the Accuracy Between a Digital Fabrication Workflow and a Conventional Fabrication Workflow for Occlusal Appliances: A Pilot Study.

PURPOSE: To compare the accuracy of occlusal stabilization appliances fabricated by digital workflows to those fabricated by conventional workflows. MATERIALS AND METHODS: In total, 10 volunteers were recruited in this single-blinded crossover study. All volunteers received two types of occlusal stabilization appliances: a digital additively manufactured stabilization splint (DS) and a conventionally fabricated splint (CS). The accuracy was assessed using a 4-point rating scale addressing two aspects of the occlusal appliances: occlusal contact and basic performance. In addition, silicone impression materials were used to assess the gap between the appliance and the maxillary arch to ensure an accurate fit. Differences were quantitatively assessed with Mann-Whitney U test and independent-sample t test. RESULTS: The occlusal contact rating of DS (15.90 ± 1.73) was significantly higher than that of CS (14.10 ± 1.10, P < .05). The basic performance rating of DS (8.70 ± 0.48) was also significantly higher than that of CS (7.20 ± 0.92. P < .05). Quantitative evaluation of fit accuracy revealed a statistically significant difference (P < .05), with DS (636.29 ± 268.51 µm) being superior to CS (704.2 ± 306.05 µm). CONCLUSION: The stabilization splints fabricated with a digital workflow showed better accuracy than the conventionally fabricated splints in terms of occlusal contact, basic performance, and fit accuracy. Because this is a pilot study, formal trials with a completely digital fabrication workflow will be conducted in the future.

Organoids Models of Pancreatic Duct Adenocarcinoma.

Three-dimensional (3D) organoid culture is a laboratory technique used to grow and study miniature organs that mimic the structure and function of real organs in the human body. Organoids are created from stem cells or tissue samples and are grown in a 3D matrix that allows them to self-organize into a complex, three-dimensional structure. Organoids are valuable tools for studying human biology and disease, including cancer. Pancreatic ductal adenocarcinoma (PDAC) still has the worst survival rate of common malignancies, despite recent advances in cancer treatment. Preclinical studies have shown that impaired cell death pathways, including apoptosis, necroptosis, ferroptosis, pyroptosis, and alkaliptosis, promote PDAC development. Organoid models are now widely used in the study of pancreatic cancer biology, including cell death machinery. This chapter provides step-by-step protocols for generating human or mice PDAC organoids in a 3D Matrigel system.

Developing a magnetic POCUS-guided bronchoscope for patients with suspected difficult endotracheal intubation in a general tertiary hospital: protocol for a randomised controlled study.

INTRODUCTION: Endotracheal intubation (ETI) is a crucial but risky procedure, especially among patients suspected of difficult endotracheal intubation (DTI). Bronchoscope, as an improved technique commonly used in DTI, might encounter visualisation difficulties. The magnetic point-of-care ultrasound (MGPOCUS) provides a novel visualisation from the outside and enables estimation of the relative position and trajectory of the bronchoscope. The purpose of the study was to evaluate the efficiency of MGPOCUS-guided bronchoscopy, including the time required for successful ETI, the first attempt and overall success rate, the number of attempts, complications, and satisfaction with the visualization of the procedures. METHODS AND ANALYSIS: The study is a randomised, parallel-group, single-blinded, single-centre study. Participants (n=108) will be recruited by the primary anaesthesiologist and randomised to groups of ETI with bronchoscope or MGPOCUS-guided bronchoscope. The primary outcome is the time taken to the first-attempt success ETI. Secondary outcomes include procedure time, the first-attempt and overall success, complications, and satisfaction of visualisation. Cox regression with Bonferroni correction and linear mixed regression will be used to analyse the outcomes. ETHICS AND DISSEMINATION: The trial protocol was approved by the ethics committees at the Peking Union Medical College Hospital (Institutional Review Board #ZS-3428). Findings will be disseminated through conference presentations and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05647174.

Association of intraoperative hypotension and postoperative acute kidney injury after adrenalectomy for pheochromocytoma: a retrospective cohort analysis.

BACKGROUND: Perioperative acute kidney injury (AKI) has been one of the leading causes of morbidity and mortality for surgical patients. Pheochromocytoma is a rare, catecholamine-secreting neuroendocrine neoplasm characterized by typical long-term hypertension that needs surgical resection. Our objective was to determine whether intraoperative mean arterial pressures (MAPs) less than 65 mmHg are associated with postoperative AKI after elective adrenalectomy in patients with pheochromocytoma. METHODS: We performed a retrospective review of patients undergoing adrenalectomy for pheochromocytoma between 1991 and 2019 at Peking Union Medical College Hospital, Beijing, China. Two intraoperative phases, before and after tumor resection, were recognized based on distinctly different hemodynamic characteristics. The authors evaluated the association between AKI and each blood pressure exposure in these two phases. The association between the time spent under different absolute and relative MAP thresholds and AKI was then evaluated adjusting for potential confounding variables. RESULTS: We enrolled 560 cases with 48 patients who developed AKI postoperatively. The baseline and intraoperative characteristics were similar in both groups. Though time-weighted average MAP was not associated with postoperative AKI during the whole operation (OR 1.38; 95% CI, 0.95-2.00; P = 0.087) and before tumor resection phase (OR 0.83; 95% CI, 0.65-1.05; P = 0.12), both time-weighted MAP and time-weighted percentage changes from baseline were strongly associated with postoperative AKI after tumor resection, with OR 3.50, 95% CI (2.25, 5.46) and 2.03, 95% CI (1.56, 2.66) in the univariable logistic analysis respectively, and with OR 2.36, 95% CI (1.46, 3.80) and 1.63, 95% CI (1.23, 2.17) after adjusting sex, surgical type (open vs. laparoscopic) and estimated blood loss in the multiple logistic analysis. At any thresholds of MAP less than 85, 80, 75, 70, and 65 mmHg, prolonged exposure was associated with increased odds of AKI. CONCLUSIONS: We found a significant association between hypotension and postoperative AKI in patients with pheochromocytoma undergoing adrenalectomy in the period after tumor resection. Optimizing hemodynamics, especially blood pressure after the adrenal vessel ligation and tumor is resected, is crucial for the prevention of postoperative AKI in patient with pheochromocytoma, which could be different from general populations.

Activating an Adaptive Immune Response with a Telomerase-Mediated Telomere Targeting Therapeutic in Hepatocellular Carcinoma.

A select group of patients with hepatocellular carcinomas (HCC) benefit from surgical, radiologic, and systemic therapies that include a combination of anti-angiogenic and immune-checkpoint inhibitors. However, because HCC is generally asymptomatic in its early stages, this not only leads to late diagnosis, but also to therapy resistance. The nucleoside analogue 6-thio-dG (THIO) is a first-in-class telomerase-mediated telomere-targeting anticancer agent. In telomerase expressing cancer cells, THIO is converted into the corresponding 5'-triphosphate, which is efficiently incorporated into telomeres by telomerase, activating telomere damage responses and apoptotic pathways. Here, we show how THIO is effective in controlling tumor growth and, when combined with immune checkpoint inhibitors, is even more effective in a T-cell-dependent manner. We also show telomere stress induced by THIO increases both innate sensing and adaptive antitumor immunity in HCC. Importantly, the extracellular high-mobility group box 1 protein acts as a prototypical endogenous DAMP (Damage Associated Molecular Pattern) in eliciting adaptive immunity by THIO. These results provide a strong rationale for combining telomere-targeted therapy with immunotherapy.

Application effect of perioperative nursing mediated by 3D printing and mind mapping in gynecological tumor laparoscopy.

Probing influence by perioperative nursing mediated by 3D printing and mind mapping in gynecological tumor laparoscopy. 90 subjects divided into three groups: A (n=30), B (n=30) and C (n=30). Each group was given a different type of nursing intervention postoperative recovery (postoperative anal gas exhausting time, eating time, hospital stay, leaving bed-time, and drainage tube extraction time) were compared among the three groups. Hamilton Anxiety Scale (HAMA)/Hamilton Depression Scale (HAMD), strategies Used by People to Promote Health (SUPPH), Generic quality-of-life Inventory (GQOLI-74) scores and complication rates were compared among the three groups. The postoperative recovery of group A and B was better than group C, and group A was better than group B (P<0.05). Post-intervening, HAMA/HAMD scorings within groups A/B reduced compared with group C, with group A＞group B (P<0.05). The complication rate of group A and B was lower than that of group C (P<0.05). Perioperative nursing mediated by 3D printing and mind mapping works well.

[Application of psychological scales recommended by DC/TMD in patients with temporomandibular joint disorders].

PURPOSE: To observe psychological conditions such as anxiety, depression and somatic symptoms of temporomandibular disorders(TMD) patients using psychological scales recommended by DC/TMD and evaluate their clinical significance as the psychological axis for TMD diagnosis. METHODS: The experimental group included 100 TMD patients, and the control group comprised 100 normal prosthodontics outpatients without TMD symptoms. General information were collected including age, gender, education level, and personal income. The anxiety disorder scale (Generalized Anxiety Disorder-7, GAD-7), depression symptom scale (Patient Health Questionnaire-9, PHQ-9) and Patient Health Questionnaire-15 (PHQ-15) were used to evaluate patients' psychological conditions. SPSS 20.0 software package was used for data analysis. RESULTS: Patients less than 30 years old and between 30-50 years had similar TMD occurrence rates, both significantly higher than those older than 50 years old(P＜0.05). The proportion of highly educated patients in TMD group was significantly higher than that in the control group(P＜0.05), while the income level was not a risk factor for TMD (P=0.642). The incidence and average scores of anxiety, not the depression or somatic symptoms, in experimental group were significantly higher than the control group(P＜0.05). The level of anxiety and depression in painful TMD patients was significantly higher than patients with joint disease(P＞0.05). CONCLUSIONS: Gender(female), age (＜50 years old) and high education level (undergraduate and above) are risk factors of TMD, but the income level is irrelevant. The incidence and scores of anxiety in TMD patients are higher than normal prosthodontics outpatients, while there is no significant difference in the incidence of depression and somatic symptoms between two groups.

Identification of HPCAL1 as a specific autophagy receptor involved in ferroptosis.

Selective macroautophagy/autophagy maintains cellular homeostasis through the lysosomal degradation of specific cellular proteins or organelles. The pro-survival effect of selective autophagy has been well-characterized, but the mechanism by which it drives cell death is still poorly understood. Here, we use a quantitative proteomic approach to identify HPCAL1 (hippocalcin like 1) as a novel autophagy receptor for the selective degradation of CDH2 (cadherin 2) during ferroptosis. HPCAL1-dependent CDH2 depletion increases susceptibility to ferroptotic death by reducing membrane tension and favoring lipid peroxidation. Site-directed mutagenesis aided by bioinformatic analyses revealed that the autophagic degradation of CDH2 requires PRKCQ (protein kinase C theta)-mediated HPCAL1 phosphorylation on Thr149, as well as a non-classical LC3-interacting region motif located between amino acids 46-51. An unbiased drug screening campaign involving 4208 small molecule compounds led to the identification of a ferroptosis inhibitor that suppressed HPCAL1 expression. The genetic or pharmacological inhibition of HPCAL1 prevented ferroptosis-induced tumor suppression and pancreatitis in suitable mouse models. These findings provide a framework for understanding how selective autophagy promotes ferroptotic cell death.Abbreviations: ANXA7: annexin A7; ARNTL: aryl hydrocarbon receptor nuclear translocator like; CCK8: cell counting kit-8; CDH2: cadherin 2; CETSAs: cellular thermal shift assays; CPT2: carnitine palmitoyltransferase 2; DAMP, danger/damage-associated molecular pattern; DPPH: 2,2-diphenyl-1-picrylhydrazyl; DFO: deferoxamine; EBNA1BP2: EBNA1 binding protein 2; EIF4G1: eukaryotic translation initiation factor 4 gamma 1; FBL: fibrillarin; FKBP1A: FKBP prolyl isomerase 1A; FTH1: ferritin heavy chain 1; GPX4: glutathione peroxidase 4; GSDMs: gasdermins; HBSS: Hanks' buffered salt solution; HMGB1: high mobility group box 1; HNRNPUL1: heterogeneous nuclear ribonucleoprotein U like 1; HPCAL1: hippocalcin like 1; H1-3/HIST1H1D: H1.3 linker histone, cluster member; IKE: imidazole ketone erastin; KD: knockdown; LDH: lactate dehydrogenase; LIR: LC3-interacting region; MAGOH: mago homolog, exon junction complex subunit; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MDA: malondialdehyde; MLKL: mixed lineage kinase domain like pseudokinase; MPO: myeloperoxidase; MTOR: mechanistic target of rapamycin kinase; OE: overexpressing; OSTM1: osteoclastogenesis associated transmembrane protein 1; PRKC/PKC: protein kinase C; PRKAR1A: protein kinase cAMP-dependent type I regulatory subunit alpha; PRDX3: peroxiredoxin 3; PTGS2: prostaglandin-endoperoxide synthase 2; ROS: reactive oxygen species; SLC7A11: solute carrier family 7 member 11; SLC40A1: solute carrier family 40 member 1; SPTAN1: spectrin alpha, non-erythrocytic 1; STS: staurosporine; UBE2M: ubiquitin conjugating enzyme E2 M; ZYX: zyxin.

A noncanonical function of EIF4E limits ALDH1B1 activity and increases susceptibility to ferroptosis.

Ferroptosis is a type of lipid peroxidation-dependent cell death that is emerging as a therapeutic target for cancer. However, the mechanisms of ferroptosis during the generation and detoxification of lipid peroxidation products remain rather poorly defined. Here, we report an unexpected role for the eukaryotic translation initiation factor EIF4E as a determinant of ferroptotic sensitivity by controlling lipid peroxidation. A drug screening identified 4EGI-1 and 4E1RCat (previously known as EIF4E-EIF4G1 interaction inhibitors) as powerful inhibitors of ferroptosis. Genetic and functional studies showed that EIF4E (but not EIF4G1) promotes ferroptosis in a translation-independent manner. Using mass spectrometry and subsequent protein-protein interaction analysis, we identified EIF4E as an endogenous repressor of ALDH1B1 in mitochondria. ALDH1B1 belongs to the family of aldehyde dehydrogenases and may metabolize the aldehyde substrate 4-hydroxynonenal (4HNE) at high concentrations. Supraphysiological levels of 4HNE triggered ferroptosis, while low concentrations of 4HNE increased the cell susceptibility to classical ferroptosis inducers by activating the NOX1 pathway. Accordingly, EIF4E-dependent ALDH1B1 inhibition enhanced the anticancer activity of ferroptosis inducers in vitro and in vivo. Our results support a key function of EIF4E in orchestrating lipid peroxidation to ignite ferroptosis.

Incidence and risk factors for myocardial injury after laparoscopic adrenalectomy for pheochromocytoma: A retrospective cohort study.

Background: Pheochromocytoma is a rare catecholamine-secreting tumor. Tumor resection remains a high-risk procedure due to intraoperative hemodynamic instability nowadays, which may lead to myocardial injury. We aimed to determine the incidence and associated risk factors for myocardial injury after laparoscopic adrenalectomy for pheochromocytoma. Methods: Adult patients (n=350, American Society of Anesthesiology physical status 1-3) who underwent elective laparoscopic adrenalectomy for pheochromocytoma under general anesthesia between January 31, 2013 and January 31, 2020 were included in this observational, retrospective, single-center, cohort study. Blood troponin I levels were measured before and during the first 2 days after surgery. Myocardial injury was defined as an elevated troponin I level exceeding the 99th percentile upper reference limit due to cardiac ischemic causes. Results: Myocardial injury occurred in 42/350 patients (12.0%, 95% confidence interval: 9.0%-15.9%). In multivariable analysis (adjusted odds ratios [95% confidence intervals]), previous ischemic heart disease or stroke (5.04 [1.40-18.08]; P=0.013), intraoperative heart rate >115 bpm (2.55 [1.06-6.12]; P=0.036), intraoperative systolic blood pressure >210 mmHg (2.38 [1.00-5.66]; P=0.049), and perioperative decrease in hemoglobin level(1.74 [1.15-2.64] per g/dL decrease; P=0.008) were associated with an increased risk of myocardial injury. For the cumulative duration of dichotomized intraoperative hemodynamics, multivariable analysis showed that intraoperative heart rate >115 bpm for >1 minute (2.67 [1.08-6.60]; P=0.034) and systolic blood pressure >210 mmHg for >1 minute (3.78 [1.47-9.73]; P=0.006) were associated with an increased risk of myocardial injury. The risk of myocardial injury progressively increased with a longer cumulative duration of intraoperative tachycardia and hypertension. Conclusions: There is a high incidence of myocardial injury after laparoscopic adrenalectomy for pheochromocytoma. The identified risk factors may assist physicians in detecting high-risk patients and providing guidance for intraoperative hemodynamics and perioperative hemoglobin management.

Application Effect of Cluster-Based Care in Patients with Hypertensive Disorders of Pregnancy and Osteoarthritis.

Objective: To explore the application effect of cluster-based care in patients with hypertensive disorders of pregnancy and osteoarthritis. Methods: The clinical data of 60 patients with hypertensive disorders of pregnancy and osteoarthritis in our hospital were retrospectively analyzed, among which those receiving routine care from January 2020 to December 2020 were grouped into the control group (30 patients), and those receiving cluster-based care from January 2021 to January 2022 were grouped into the research group (30 patients). Psychological status, care satisfaction, and pregnancy outcomes were compared between the two groups. Results: After intervention, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores in the research group were lower than those in the control group (P < 0.05). There was no statistical significance in the difference of the modes of delivery between the two groups (χ 2 = 1.763, P > 0.05). Patients in the research group had a lower incidence of perinatal complications than those in the control group (χ 2 = 5.689, P < 0.05). And the satisfaction rate of care in the research group (93.33% vs 70%) was higher than that in the control group (χ 2 = 4.238, P < 0.05). Conclusion: Cluster-based care can reduce patients' negative mood, increase their satisfaction, and improve the maternal and infant outcomes. This type of care offers better quality care measures for patients with pregnancy hypertension and osteoarthritis, and has a wide clinical application prospect.