Redox Dysregulation of Vascular Smooth Muscle Sirtuin-1 in Thoracic Aortic Aneurysm in Marfan Syndrome.

BACKGROUND: Thoracic aortic aneurysms (TAAs) are abnormal aortic dilatations and a major cardiovascular complication of Marfan syndrome. We previously demonstrated a critical role for vascular smooth muscle (VSM) SirT1 (sirtuin-1), a lysine deacetylase, against maladaptive aortic remodeling associated with chronic oxidative stress and aberrant activation of MMPs (matrix metalloproteinases). METHODS: In this study, we investigated whether redox dysregulation of SirT1 contributed to the pathogenesis of TAA using fibrillin-1 hypomorphic mice (Fbn1mgR/mgR), an established model of Marfan syndrome prone to aortic dissection/rupture. RESULTS: Oxidative stress markers 3-nitrotyrosine and 4-hydroxynonenal were significantly elevated in aortas of patients with Marfan syndrome. Moreover, reversible oxidative post-translational modifications (rOPTM) of protein cysteines, particularly S-glutathionylation, were dramatically increased in aortas of Fbn1mgR/mgR mice, before induction of severe oxidative stress markers. Fbn1mgR/mgR aortas and VSM cells exhibited an increase in rOPTM of SirT1, coinciding with the upregulation of acetylated proteins, an index of decreased SirT1 activity, and increased MMP2/9 activity. Mechanistically, we demonstrated that TGFß (transforming growth factor beta), which was increased in Fbn1mgR/mgR aortas, stimulated rOPTM of SirT1, decreasing its deacetylase activity in VSM cells. VSM cell-specific deletion of SirT1 in Fbn1mgR/mgR mice (SMKO-Fbn1mgR/mgR) caused a dramatic increase in aortic MMP2 expression and worsened TAA progression, leading to aortic rupture in 50% of SMKO-Fbn1mgR/mgR mice, compared with 25% of Fbn1mgR/mgR mice. rOPTM of SirT1, rOPTM-mediated inhibition of SirT1 activity, and increased MMP2/9 activity were all exacerbated by the deletion of Glrx (glutaredoxin-1), a specific deglutathionylation enzyme, while being corrected by overexpression of Glrx or of an oxidation-resistant SirT1 mutant in VSM cells. CONCLUSIONS: Our novel findings strongly suggest a causal role of S-glutathionylation of SirT1 in the pathogenesis of TAA. Prevention or reversal of SirT1 rOPTM may be a novel therapeutic strategy to prevent TAA and TAA dissection/ruptures in individuals with Marfan syndrome, for which, thus far, no targeted therapy has been developed.

Goal-Directed, Evidence-Based Care Reduces the Incidence of Perioperative Stress Injury.

Objective: This study aimed to investigate the clinical impact of goal-oriented, evidence-based nursing in preventing perioperative stress injuries. Methods: A total of 380 patients undergoing surgery were allocated into either the control or study group. The study group received goal-oriented, evidence-based nursing, while the control group received routine nursing care. Various perioperative indicators, including operating time, position change time, intraoperative bleeding, and length of hospitalization, were assessed and compared between the two groups. Additionally, the Mini-Nutritional Assessment (MNA) score, Munro score, incidence of stress injuries, and nursing satisfaction rate were compared. Patients with perioperative pressure sores (PS) were further evaluated using the Pressure Ulcer Healing Score (PUSH), Braden Stress Injury Scale (Braden), visual analogue scale of pain (VAS), and wound healing time. Results: The study group exhibited higher MNA levels during and after the operation, while Munro levels were lower compared to the control group (P < .05). The study group demonstrated a shorter length of stay and quicker body position changes than the control group. Incidence of pressure sores (PS) was lower in the study group, accompanied by higher nursing satisfaction. PS patients in the study group had lower VAS and PUSH scores, higher Braden scores, and shorter wound healing times than those in the control group. Conclusion: This study highlights the efficacy of goal-oriented, evidence-based nursing in reducing perioperative stress injuries, advocating its adoption for improved care and patient outcomes. However, the single-center design limits generalizability, necessitating further validation. Ultimately, this approach signifies a step forward in nursing practice, promising better patient recovery and satisfaction.

Accelerating H2 Evolution by Anodic Semi-dehydrogenation of Tetrahydroisoquinolines in Water over Co3 O4 Nanoribbon Arrays Decorated Nickel Foam.

Coupling the H2 evolution reaction in water with thermodynamically favorable organic oxidation reactions is highly desirable, because it can enhance the energy conversion efficiency compared with electrocatalytic water splitting, and produce value-added chemicals instead of O2 in the anodic reaction. Herein, Co3 O4 nanoribbon arrays in situ grown on nickel foam (Co3 O4 @NF) was employed as an effective electrocatalyst for the selective oxidation of tetrahydroisoquinolines (THIQs). Various value-added semi-dehydrogenation products including dihydroisoquinolines with electro-deficient or -rich groups could be obtained with moderate yields and faradaic efficiencies. Benefitting from the rich surface active sites of Co3 O4 @NF, a two-electrode (Co3 O4 @NF||Pt) electrolytic system drove a benchmark current density of 10 mA cm-2 at a cell voltage as low as 1.446 V in 1.0 M KOH aqueous solution containing 0.02 M THIQ, which was reduced by 174 mV in comparison with that of overall water splitting.

Transcriptomic analysis of adult zebrafish heart and brain in response to 2, 6-dichloro-1, 4-benzoquinone exposure.

Halobenzoquinones (HBQs) are emerging and widespread disinfection byproducts (DBPs), but their toxicological mechanisms to aquatic organisms remain elusive. Herein, we evaluated oxidative stress, cardiac toxicity, and cerebral toxicity after 2, 6-dichloro-1, 4-benzoquinone (2,6-DCBQ) exposure in zebrafish. Adult zebrafish were respectively exposed to 0.25, 0.5, and 1 µM 2,6-DCBQ for 96 h. The mortality rate of 2,6-DCBQ (1 µM) was 10%, while the LC50 value was 1.532 µM. Besides, 2,6-DCBQ exposure caused irregularity and elimination of myocardial fiber in the heart, and the pyknosis of nuclears and the agglutination of chromatin in the brain. We measured the 2,6-DCBQ-induced oxidative stresses in the heart and brain. Additionally, the glutathione (GSH) content, superoxide dismutase (SOD) activity, catalase (CAT) activity, and total antioxidant capacity (T-AOC) were significantly inhibited. To better understand the potential toxicity of 2,6-DCBQ, transcriptomic analysis was performed in the control and 1 µM group after 96 h exposure. As a result, 545 and 1228 differentially expressed genes (DEGs) were detected in the heart and brain, respectively. GO analysis revealed that these DEGs were primarily enriched in blood vessel development, vasculature development, and oxidoreductase activity in the heart; response to stimulus, nervous system development, and oxidoreductase activity in the brain. KEGG enrichment analysis indicated that the DEGs were mainly enriched in VEGF signaling pathway and vascular smooth muscle contraction pathway in the heart; neuroactive ligand-receptor interaction, and NOD-like receptor signaling pathway in the brain. These findings exposed the underlying toxicity mechanism of 2,6-DCBQ exposure on zebrafish cardiovascular and brain systems.

[Discussion on Management Model of Medical Devices for Clinical Trials].

By analyzing the main problems existing in the current management of medical devices for clinical trials, this study proposes a feasible management model and specific requirements for acceptance, distribution, storage and recovery combining with the characteristics of medical consumable equipment and diagnostic reagent, which provides a favorable guarantee for the authenticity and reliability of clinical trials.

Crystal Morphology of Poly(3-hydroxybutyrate) on Amorphous Poly(vinylphenol) Substrate.

The crystalline morphology and orientation of poly(3-hydroxybutyrate) (PHB) thin film on the poly(vinylphenol) (PVPh) sublayer with different thickness was studied by atomic force microscopy, X-ray diffraction, and infrared spectroscopy. PVPh sublayer influences the morphology of PHB greatly. Although edge-on lamellae form on both Si and PVPh surfaces at relatively lower crystallization temperature, the morphology of them is quite different. It appears as sheaflike edge-on lamellar morphology on PVPh sublayer. In addition, the edge-on lamellae prefer to form on the PVPh sublayers at much higher crystallization temperature compared with that on Si wafer. The PVPh layer thickness also influences the crystalline morphology of PHB. On a 30 nm thick PVPh layer, sheaflike edge-on lamellae form in a wide range of crystallization temperatures. When the PVPh thickness increases to 65 nm, fingerlike morphology is observed when the crystallization temperature is lower than 95 °C. The fingerlike morphology is caused by a diffusion-limited aggregation process, and it requires an optimum condition. Thickness ratio between PHB and PVPh sublayer and temperature are two key factors for the formation of fingerlike morphology.

Stable isotope labeling-based two-step derivatization strategy for analysis of Phosphopeptides.

Investigating site-specific protein phosphorylation remains a challenging task. The present study introduces a two-step chemical derivatization method for accurate identification of phosphopeptides. Methylamine neutralizes carboxyl groups, thus reducing the adsorption of non-phosphorylated peptides during enrichment, while dimethylamine offers a cost-effective reagent for stable isotope labeling of phosphorylation sites. The derivatization improves the mass spectra obtained through liquid chromatography-tandem mass spectrometry. The product ions at m/z 58.07 and 64.10 Da, resulting from dimethylamine-d0 and dimethylamine-d6 labeled phosphorylation sites respectively, can serve as report ions. Derivatized phosphopeptides from casein demonstrate enhanced ionization and formation of product ions, yielding a significant increase in the number of identifiable peptides. When using the parallel reaction monitoring technique, it is possible to distinguish isomeric phosphopeptides with the same amino acid sequence but different phosphorylation sites. By employing a proteomic software and screening the report ions, we identified 29 endogenous phosphopeptides in 10 µL of human saliva with high reliability. These findings indicate that the two-step derivatization strategy has great potential in site-specific phosphorylation and large-scale phosphoproteomics research. SIGNIFICANCE: There is a significant need to improve the accuracy of identifying phosphoproteins and phosphopeptides and analyzing them quantitatively. Several chemical derivatization techniques have been developed to label phosphorylation sites, thus enabling the identification and relative quantification of phosphopeptides. Nevertheless, these methods have limitations, such as incomplete conversion or the need for costly isotopic reagents. Building upon previous contributions, our study moves the field forward due to high efficiency in site-specific labeling, cost-effectiveness, improved sensitivity, and comprehensive product ion coverage. Using the two-step derivatization approach, we successfully identified 29 endogenous phosphopeptides in 10 µL of human saliva with high reliability. The outcomes underscore the possibility of the method for site-specific phosphorylation and large-scale phosphoproteomics investigations.

Exploring the casual association between gut microbiome, circulating inflammatory cytokines and chronic pancreatitis: A Mendelian randomization analysis.

It has been established that gut dysbiosis contributed to the pathogenesis of digestive disorders. We aimed to explore the causal relationships between intestinal microbiota, circulating inflammatory cytokines and chronic pancreatitis (CP). Summary statistics of genome-wide association studies (GWAS) of intestinal microbiome was retrieved from the MiBioGen study and the GWAS data of 91 circulating inflammatory cytokines and CP were obtained from the GWAS catalog. The 2-sample bidirectional Mendelian randomization (MR) analysis was performed between gut microbiota, circulating inflammatory cytokines and CP, in which the inverse variance weighted (IVW) method was regarded as the primary analysis approach. To prove the reliability of the causal estimations, multiple sensitivity analyses were utilized. IVW results revealed that genetically predicted 2 genera, including Sellimonas and Eubacteriumventriosumgroup, and plasm C-C motif chemokine 23 (CCL23) level were positively associated with CP risk, while genus Escherichia Shigella, Eubacteriumruminantiumgroup and Prevotella9, and plasma Caspase 8, Adenosine Deaminase (ADA), and SIR2-like protein 2 (SIRT2) level, demonstrated an ameliorative effect on CP. Leave-one-out analysis confirmed the robustness of the aforementioned causal effects and no significant horizontal pleiotropy or heterogeneity of the instrumental variables was detected. However, no association was found from the identified genera to the CP-related circulating inflammatory cytokines. Besides, the reverse MR analysis demonstrated no causal relationship from CP to the identified genera and circulating inflammatory cytokines. Taken together, our comprehensive analyses offer evidence in favor of the estimated causal connections from the 5 genus-level microbial taxa and 4 circulating inflammatory cytokines to CP risk, which may help to reveal the underlying pathogenesis of CP.

Expert Consensus on Ion Channel Drugs for Chronic Pain Treatment in China.

Ion channel drugs have been increasing used for chronic pain management with progress in the development of selective calcium channel modulators. Although ion channel drugs have been proven safe and effective in clinical practice, uncertainty remains regarding its use to treat chronic pain. To standardize the clinical practice of ion channel drug for the treatment of chronic pain, the National Health Commission Capacity Building and Continuing Education Center for Pain Diagnosis and Treatment Special Ability Training Project established an expert group to form an expert consensus on the use of ion channel drugs for the treatment of chronic pain after repeated discussions on existing medical evidence combined with the well clinical experience of experts. The consensus provided information on the mechanism of action of ion channel drugs and their recommendations, caution use, contraindications, and precautions for their use in special populations to support doctors in their clinical decision-making.

Case report: Spinal cord stimulation in the treatment of pediatric erythromelalgia.

Introduction: In children, erythromelalgia is a rare chronic pain syndrome characterized by erythema, severe burning pain, and itching of affected feet. Unfortunately, there is no definitive therapy available currently. Case report: Here, we report a case of primary erythromelalgia and the treatment response in a 10-year-old boy, whose genetic findings for mutations in the SCN9A gene were positive and skin biopsy results were diagnosed as small fiber neuropathy, while he has suffered from excruciating burning pain, itching, erythema, and recurrent infections over the past 3 years. He did not respond well to conventional treatment, and the only way to receive minimal relief was to immerse his feet in ice water. After a successful trial of spinal cord stimulation (SCS), the implantable pulse generator (IPG) was successfully implanted without complications, and it proved partial response to therapy. Conclusion: There is no specific, efficient treatment for pediatric erythromelalgia currently, but this case demonstrates neuromodulation serves as part of the multimodal regimen to treat pediatric erythromelalgia.

Efficacy and safety of oropharyngeal muscle strength training on poststroke oropharyngeal dysphagia: a systematic review and meta-analysis.

OBJECTIVES: To investigate how oropharyngeal muscle strength training affected the safety and performance of swallowing in patients with poststroke oropharyngeal dysphagia. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane Central Register of Controlled of Trials, Web of Science, PubMed, Embase databases and ClinicalTrials.gov were systematically searched, for publications in English, from database inception to December 2022. ELIGIBILITY CRITERIA: Studies comparing the effect of oropharyngeal muscle strength training with conventional dysphagia therapy in patients with poststroke. Penetration-Aspiration Scale (PAS) and Functional Oral Intake Scale (FOIS) were assessed as the main outcomes. DATA EXTRACTION AND SYNTHESIS: Two researchers independently screened the literature, extracted data and evaluated the quality of the included studies, with disagreements resolved by another researcher. The Cochrane risk-of-bias tool was used to assess the risk of bias. Review Manager V.5.3 was employed for the meta-analysis. Random effect models were used for meta-analysis. RESULTS: Seven studies with 259 participants were included in this meta-analysis. The results showed that oropharyngeal muscle strength training could reduce PAS score compared with conventional dysphagia therapy (mean difference=-0.98, 95% CI -1.34 to -0.62, p<0.0001, I2=28%). The results also showed that oropharyngeal muscle strength training could increase FOIS score (mean difference=1.04, 95% CI 0.55 to 1.54, p<0.0001, I2=0%) and the vertical displacement of the hyoid bone (mean difference=0.20, 95% CI 0.01 to 0.38, p=0.04, I2=0%) compared with conventional dysphagia therapy. CONCLUSION: In patients with poststroke oropharyngeal dysphagia, oropharyngeal muscle strength training can improve swallowing safety and performance. PROSPERO REGISTRATION NUMBER: CRD42022302471.

Safety and performance of oropharyngeal muscle strength training in the treatment of post-stroke dysphagia during oral feeding: protocol for a systematic review and meta-analysis.

INTRODUCTION: Dysphagia is a common functional disorder after stroke. Most patients post-stroke are incapable of oral feeding, which often leads to complications such as malnutrition, aspiration pneumonia and dehydration that seriously affect the quality of life of patients. Oropharyngeal muscle strength training is a major method of swallowing training, and recent studies have focused on healthy adults, elderly persons, and patients with head and neck cancer or neurodegenerative diseases; but there have been few studies on such training in patients with post-stroke dysphagia. Our study aims to systematically review the safety and performance of oropharyngeal muscle strength training in the treatment of post-stroke dysphagia during oral feeding. METHODS AND ANALYSIS: The Cochrane Library, Web of Science, PubMed, Embase and ClinicalTrials.gov databases will be systematically searched, and all relevant articles in English from the establishment of the databases to January 2022 will be reviewed. The study will be conducted in accordance with the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and will be reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. The primary outcome measures include the Penetration-Aspiration Scale and the Functional Oral Intake Scale. Two authors will independently screen the articles, extract the data and assess the study quality. Any disagreements during this process will be resolved by discussion or by consultation with a third author. Next, quantitative or qualitative, subgroup and sensitivity analyses of the included literature data will be performed as appropriate. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review as no primary data collection will be required. The results of the present study will be published in a peer-reviewed journal in the field of deglutition disorders. PROSPERO REGISTRATION NUMBER: CRD42022302471.

Redox-responsive polyurethane-polyurea nanoparticles targeting to aortic endothelium and atherosclerosis.

Aortic endothelial cell dysfunction is an early trigger of atherosclerosis, the major cause of the cardiovascular disease (CVD). Nanomedicines targeting vascular endothelium and lesions hold great promise as therapeutic solutions to vascular disorders. This study investigates the vascular delivery efficacy of polyurethane-polyurea nanocapsules (Puua-NCs) with pH-synchronized shell cationization and redox-triggered release. Fluorescent lipophilic dye DiI was encapsulated into Puua-NCs of variable sizes and concentrations. In vitro cellular uptake studies with human aortic endothelial cells showed that these Puua-NCs were taken up by cells in a dose-dependent manner. In apolipoprotein E-deficient mice fed a Western diet, a model of atherosclerosis, circulating Puua-NCs were stable and accumulated in aortic endothelium and lesions within 24 hours after intravenous administration. Treatment with thiol-reducing and oxidizing reagents disrupted the disulfide bonds on the surface of internalized NCs, triggering disassembly and intracellular cargo release. Ultimately, Puua-NCs are a potential redox-controllable cardiovascular drug delivery system.

Antibiotic and glucocorticoid-induced recapitulated hematological remission in acute myeloid leukemia: A case report and review of literature.

BACKGROUND: Leukemic hematopoietic cells acquire enhanced self-renewal capacity and impaired differentiation. The emergence of symptomatic leukemia also requires the acquisition of a clonal proliferative advantage. Untreated leukemia patients usually experience an aggressive process. However, spontaneous remission occasionally occurs in patients with acute myeloid leukemia (AML), most frequently after recovery from a febrile episode, and this is generally attributed to the triggering of antineoplastic immunity. There may be another explanation for the spontaneous remission as implicated in this paper. CASE SUMMARY: A 63-year-old Chinese man presented with high fever, abdominal pain and urticaria-like skin lesions. He was diagnosed with AML-M4 with t(8;21) (q22;q22)/RUNX1-RUNX1T1 based on morphological, immunological, cytogenetic and molecular analyses. He had a complex chromosome rea-rrangement of 48,XY,t(8;21)(q22;q22),+13,+13[9]/49,idem,+mar[9]/49,idem,+8[2]. He also had a mutated tyrosine kinase domain in fms-like tyrosine kinase 3 gene. He was treated with antibiotics and glucocorticoids for gastrointestinal infection and urticaria-like skin lesions. The infection and skin lesions were quickly resolved. Unexpectedly, he achieved hematological remission along with resolution of the febrile episode, gastrointestinal symptoms and skin lesions. Notably, after relapse, repeating these treatments resulted in a return to hematological remission. Unfortunately, he demonstrated strong resistance to antibiotic and glucocorticoid treatment after the second relapse and died of sepsis from bacterial infection with multidrug resistance. The main clinical feature of this patient was that symptomatic AML emerged with flaring of the gut inflammatory disorder and it subsided after resolution of the inflammation. Learning from the present case raises the possibility that in a subgroup of AML patients, the proliferative advantage of leukemia cells may critically require the presence of inflammatory stresses. CONCLUSION: Inflammatory stresses, most likely arising from gastrointestinal infection, may sustain the growth and survival advantage of leukemic cells.

Distribution of the population and health projects of the Joint Fund in China between 2006 and 2019.

BACKGROUND: The Joint Fund has explored the cooperation mechanism between the National Natural Science Foundation of China (NSFC) and local government, promoted the development of basic research, and created a new model system. The Joint Fund has had a huge influence on scientific and technological community, especially in the field of population and health. METHODS: Research materials and related data were drawn from the NSFC database. We used the search words "National Natural Science Foundation", "Joint Fund", population and health", and "medical codes" to obtain useful information and collect relevant data. RESULTS: From 2006 to 2019, the NSFC's Joint Fund awarded a total of 767.683 million Chinese Yuan to 590 projects, distributed in 9 local government Joint Funds and 1 enterprise Joint Fund within the field of population and health. And the NSFC-Guangdong Joint Fund has invested the most, followed by the NSFC-Yunnan Joint Fund. A total of 92 applicants' host institutions from 20 provinces and municipalities were funded by the Joint Fund in the field of population and health, of which Zhengzhou University received the largest number of projects (137), and Sun Yat-sen University received the largest amount of funding (CNY 76,230,000). CONCLUSIONS: The Joint Fund has increased investment in the field of population and health in recent years. By analyzing the characteristics of population and health projects, we identified the NSFC-Guangdong Joint Fund and NSFC-Yunnan Joint Fund invested more, and Sun Yat-sen University and Zhengzhou University received more funding projects, which may help to guide future grant applications.

Bromine and iodine species in drinking water supply system along the Changjiang River in China: Occurrence and transformation.

Bromine (Br) and iodine (I) in source water can form highly toxic brominated or iodinated disinfection byproducts in treatment plants. For the first time, the occurrence of Br and I speciation and their proportion, transformation in the drinking water supply system along the Changjiang River were investigated. 96 water samples were collected from eight drinking water treatment plants under conditions of low, normal, and flood water regimes. Total Br (TBr) and total I (TI) concentrations were quantified by inductively coupled plasma mass spectrometry (ICPMS) and inorganic Br/I forms (bromide, bromate, iodide, and iodate) were determined by high-performance liquid chromatography coupled with ICPMS. Concentrations of organic Br/I were calculated as the difference between total Br/I and inorganic Br/I. Water regimes had different effect on Br and I species, and there were different rules in untreated and treated water samples. Apparent increase of TBr and TI concentrations after water treatment were observed, which indicated the possibility of Br/I introduction by chlorine-containing disinfectant. The occurrence of TBr, TI, bromide, and total organic I in the river were investigated to increase with the direction of flow. In addition, TBr and TI concentrations correlated with the concentrations of artificial sweeteners (e.g., acesulfame and sucralose, a kind of wastewater indicator), suggesting the influence of domestic sewage on Br and I in the river. In untreated water, bromide was the main Br species, and after treatment more than 50% was transformed into organic Br. Iodoorganics were the majority of I species in raw water and were partly transformed into iodate after treatment. Overall, the Br/I species have accumulation potential in the Changjiang River and organic forms occupy high proportion in treated water samples, which should be paid more attention.

Expert consensus of Chinese Association for the Study of Pain on the non-opioid analgesics for chronic musculoskeletal pain.

Chronic musculoskeletal pain (CMP) is a common occurrence in clinical practice and there are a variety of options for the treatment of it. However, the pharmacological therapy is still considered to be a primary treatment. The recent years have witnessed the emergence of opioid crisis, yet there are no relevant guidelines on how to treat CMP with non-opioid analgesics properly. The Chinese Medical Association for the Study of Pain convened a panel meeting to develop clinical practice consensus for the treatment of CMP with non-opioid analgesics. The purpose of this consensus is to present the application of nonsteroidal anti-inflammatory drugs, serotonin norepinephrine reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, muscle relaxants, ion channel drugs and topical drugs in CMP.