Targeted inhibition of m6A demethylase FTO by FB23 attenuates allergic inflammation in the airway epithelium.

Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity-associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small-molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO-regulated transcriptome-wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue-specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL-4/IL-13-treated epithelial cells and house dust mite (HDM)-induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF-α signaling via NF-κB and epithelial-mesenchymal transition-related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23-induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM-induced mice, potentially through diverse cellular processes and epithelial-mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.

Predictive value of the single most suspicious ultrasound feature in subcentimeter thyroid nodules: a retrospective observational cohort study.

PURPOSE: Proper management of subcentimeter thyroid nodules remains challenging for both clinicians and patients. Conducting extensive sonographic research using a safe and inexpensive tool for identifying thyroid nodules is necessary. The aim of this study was to identify whether having the highest-risk ultrasound (US) characteristic suggests that US-guided fine-needle aspiration (FNA) biopsy of subcentimeter nodules is more appropriate for the identification of malignancy than active surveillance (AS) or surgery. METHODS: The data of patients with highly suspicious subcentimeter thyroid nodules and US characteristic data who underwent surgery were retrospectively examined. RESULTS: Among a total of 556 subcentimeter nodules, 223 (40.1%) were benign, and 333 (59.9%) were malignant, with a mean maximal nodule size of 8.1 mm. In addition to age younger than 45 years, several US features were significantly associated with malignancy: irregular margins, the presence of microcalcifications, and taller-than-wide shapes (P < 0.001). Multivariate analysis also revealed that a taller-than-wide shape (OR = 8.988, P = 0.0015) was an independent factor associated with malignancy in subcentimeter thyroid nodules. The diagnostic performance of preoperative FNA was classified as a malignancy, with a sensitivity of 98.4%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 76.9%. CONCLUSIONS: This is one of the few reports based on actual data of the most suspicious US features in subcentimeter thyroid nodules. A taller-than-wide shape US feature is most significantly associated with malignancy. FNA is a simple, accurate, and reliable preoperative method for diagnosing malignant subcentimeter thyroid nodules with highly suspicious US characteristics. AS was less appropriate than FNA for subcentimeter nodules with a taller-than-wide shape, especially in patients ≤ 45 years of age.

Rosiglitazone Promotes Oligodendrocyte Development and Myelin Formation of Repeated Neonatal Sevoflurane Exposure via PPARγ Signaling.

Sevoflurane is one of the most commonly used general anesthetics for children and infants. Recent research indicates that repeated exposure to sevoflurane in neonates induces cognitive and fine motor deficits. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have garnered significant attention as potential therapies for a variety of neurological conditions. In this research, we evaluated whether pretreatment with rosiglitazone in neonatal mice could address myelination defects, cognitive impairment, and fine motor dysfunction via PPARγ. The mice were exposed to 3% sevoflurane for 2 h on postnatal days 6-8 (P6-P8). Behavioral tests were conducted from P29 to P34. Additionally, we evaluated morphological and functional changes related to myelin. Our results showed that rosiglitazone pretreatment significantly ameliorated the cognitive and fine motor impairments of repeated neonatal sevoflurane exposure. In addition, rosiglitazone pretreatment promoted oligodendrocyte precursor cells (OPCs) differentiation and myelination. This suggests that rosiglitazone may be used in clinical settings to enhance the security of neonatal sevoflurane exposure. Furthermore, PPARγ and fatty acid synthase (FASN) may be mediators for rosiglitazone, which alleviates myelination defects, cognitive impairment, and fine motor dysfunction.

Alteration of the airway microbiota is associated with the progression of post-COVID-19 chronic cough in adults: a prospective study.

Cough is one of the most common symptoms observed in patients presenting with COVID-19, persisting for an extended duration following SARS-CoV-2 infection. We aim to describe the distribution of airway microbiota and explore its role in patients with post-COVID-19 chronic cough. A total of 57 patients experiencing persistent cough after infection were recruited during the Omicron wave of SARS-CoV-2 in China. Airway microbiota profiling is assessed in nasopharyngeal swab, nasal lavage, and induced sputum samples at 4 and 8 weeks after SARS-CoV-2 infection. Our findings reveal that bacterial families Staphylococcaceae, Corynebacteriaceae, and Enterobacteriaceae are the most prevalent in the upper airway, while Streptococcaceae, Lachnospiraceae, and Prevotellaceae emerge as the most prevalent bacterial families in the lower airway. An increase in the abundance of Staphylococcus in nasopharyngeal swab samples and of Streptococcus in induced sputum samples is observed after one month. Furthermore, the abundance of Staphylococcus identified in nasopharyngeal swab samples at the baseline period emerges as an insightful predictor for improvement in cough severity. In conclusion, dynamic alterations in the airway microbial composition may contribute to the post-COVID-19 chronic cough progression, while the compositional signatures of nasopharyngeal microbiota could reflect the improvement of this disease.

Manganese-derived biomaterials for tumor diagnosis and therapy.

Manganese (Mn) is widely recognized owing to its low cost, non-toxic nature, and versatile oxidation states, leading to the emergence of various Mn-based nanomaterials with applications across diverse fields, particularly in tumor diagnosis and therapy. Systematic reviews specifically addressing the tumor diagnosis and therapy aspects of Mn-derived biomaterials are lacking. This review comprehensively explores the physicochemical characteristics and synthesis methods of Mn-derived biomaterials, emphasizing their role in tumor diagnostics, including magnetic resonance imaging, photoacoustic and photothermal imaging, ultrasound imaging, multimodal imaging, and biodetection. Moreover, the advantages of Mn-based materials in tumor treatment applications are discussed, including drug delivery, tumor microenvironment regulation, synergistic photothermal, photodynamic, and chemodynamic therapies, tumor immunotherapy, and imaging-guided therapy. The review concludes by providing insights into the current landscape and future directions for Mn-driven advancements in the field, serving as a comprehensive resource for researchers and clinicians.

Comparative efficacy of commercial oral poly-herbal traditional Chinese medicine formulations combined with western medicine in benign prostatic hyperplasia management: a systematic review and network meta-analysis.

Background: Benign prostatic hyperplasia (BPH) is prevalent among the aging male population and often presents with distressing lower urinary tract symptoms. There is emerging evidence that commercial oral poly-herbal traditional Chinese medicine (TCM) formulation combined with Western medicine (WM) may offer enhanced therapeutic effects compared to WM alone in BPH treatment. Nevertheless, determining the optimal formulations for BPH remains controversial. We aimed to employ a network meta-analysis to compare and assess differences among commonly used and recommended poly-herbal TCM formulations outlined in the Chinese guidelines for BPH treatment, providing clinical medication recommendations and guidance. Methods: We extensively searched for RCTs of BPH patients that had oral poly-herbal TCM formulations and WM treatment, covering both English and Chinese databases up to 31 October 2023. The quality of the included studies was evaluated using the Cochrane risk-of-bias tool Version 2 (ROB2). A Bayesian network meta-analysis was performed to assess the effectiveness of various formulations, followed by sensitivity and subgroup analyses. Results: Our meta-analysis included 107 RCTs involving 11,037 patients across 16 oral poly-herbal TCM formulations. The quality of the selected studies was assessed as "Some concerns". Most formulations combined with WM demonstrated superior therapeutic efficacy compared to WM alone. For clinical effective rate, Jingui Shenqi pill (JGSQ) + WM had the highest-ranking probability (87.38%). Concerning International Prostate Symptom Score (IPSS) and maximum flow rate of urine, Guizhi Fuling capsule (GZFL) + WM was most effective (91.10% and 98.55%). Regarding the quality of life score and postvoid residual urine, Pulean tablet (PLA) + WM ranked first (86.71% and 91.81%). In controlling prostate volume, Huange capsule (HE) + WM demonstrated the highest efficacy (95.65%). Additionally, among the interventions, Lingze (LZ) + WM capsule exhibited the lowest incidence of adverse drug reactions (2.32%). Conclusion: Combining oral poly-herbal TCM formulations with WM may provide greater therapeutic benefits in BPH treatment compared to WM alone. JGSQ, GZFL, PLA, and HE emerged as promising treatment options. However, further rigorous empirical studies are essential to substantiate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459651, CRD 42023459651.

Effects of oropharyngeal exercises on CPAP compliance: A prospective intervention study.

PURPOSE: To investigate the effects of oropharyngeal exercise on continuous positive airway pressure (CPAP) compliance in patients with moderate to severe obstructive sleep apnea over a period of 6 months. MATERIALS AND METHODS: This study was conducted as a prospective, observational, and interventional investigation. A total of 70 patients with moderate to severe obstructive sleep apnea were randomly assigned to either the oropharyngeal exercise group (n = 44) or the sham-therapy group (n = 26). The compliance of the enrolled patients with CPAP therapy was assessed at baseline, 3-month follow-up and 6-month follow-up. Objective sleep data, questionnaire and CPAP use time were collected over a half-year period (i.e., baseline, 6 months, and 12 months). RESULTS: The study found that the average use time of CPAP within one month was significantly longer in the oropharyngeal exercises group compared to the sham-therapy group at the 3-month assessment (5.5 ± 1.2 vs 4.8 ± 1.3 h per night; p=0.030), and much significantly longer at 6-months assessment (6.0 ± 1.4 vs 4.9 ± 1.3 h per night; p=0.001). Furthermore, the average use time of CPAP increased over time, with the oropharyngeal exercises group exhibiting a more pronounced growth from baseline to the six-month follow-up (4.8 ± 1.0 h per night to 6.0 ± 1.3 h per night, p < 0.001) compared to the sham-therapy group (4.8 ± 1.3 h per night to 4.9 ± 1.3 h per night, p=0.952). Additionally, the oropharyngeal exercise group demonstrated an improvement in the Epworth sleepiness scale compared to the sham-therapy group at the 3-month follow-up (6.0 ± 2.0 vs 8.8 ± 3.2; p < 0.001), as well as decreased significantly at 6-month follow-up (p = 0.032). CONCLUSIONS: CPAP adherence can be improved with oropharyngeal exercises therapy among moderate to severe OSA patients. Notably, the average duration of CPAP usage and reduction in daytime sleepiness were maintained even after six months of oropharyngeal exercise therapy.

Comprehensive effect of Naoxintong capsule combined with Western medicine on coronary heart disease after percutaneous coronary intervention: a meta-analysis.

Aims: To systematically evaluate the comprehensive effect of combining Naoxintong capsule (NXT) with Western medicine (WM) on coronary heart disease post-percutaneous coronary intervention (PCI). Methods: Randomized controlled trials (RCTs) of NXT for patients with CHD after PCI were systematically searched across multiple databases, including the Cochrane Library, PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP), and Wan Fang, from inception until 31 January 2023. Study selection, data extraction, and quality assessment were performed by two independent reviewers. The quality of the included studies was evaluated using version 2 of the Cochrane risk-of-bias tool (RoB 2), and data analysis was performed using R4.2.2. Results: Fifteen RCTs conducted between 2011 and 2022 and involving 1,551 patients were identified, with 774 and 777 patients in the experimental and control groups respectively. It was found that the NXT and WM combination was superior to the WM therapy alone in terms of the effective clinical rate (odds ratio [OR] = 4.69, 95% confidence interval [CI] = 2.13-10.30), effective rate in electrocardiogram (OR = 6.92, 95% CI = 3.44-13.92), effective rate in angina (OR = 5.90, 95% CI = 3.04-11.46), left ventricular ejection fraction (mean difference [MD] = 4.94, 95% CI = 2.89-6.99), brain natriuretic peptide (MD = -294.00, 95% CI = -584.60 to -3.39), creatine kinase-MB (MD = -7.82, 95% CI = -13.26 to -2.37), major adverse cardiovascular events (OR = 0.24, 95% CI = 0.14-0.43), maximum platelet aggregation rate (MD = -8.33, 95% CI = -11.64 to -5.01), and Chinese medicine evidence score (OR = 9.79, 95% CI = 3.57-26.85). However, there was no significant difference in cardiac troponin I level reduction (MD = -0.13, 95% CI = 0.35-0.09) or the occurrence of adverse medicine events (OR = 0.92, 95% CI = 0.41-2.05). Meta-regression and subgroup analyses indicated that NXT capsule dosage, treatment duration, and patient baseline characteristics contributed to the heterogeneity. Conclusion: A combination of NXT and WM can improve clinical outcomes in patients undergoing PCI. However, further studies are needed to confirm the reliability and safety of this combined treatment approach. Systematic Review Registration: PROSPERO, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=369174, Identifier CRD42022369174.

Case report of scrub typhus complicated by hypokalemia and multiple organ dysfunction syndrome.

CONTEXT: Scrub typhus, caused by Orientia tsutsugamushi, has a wide range of clinical manifestations, including meningoencephalitis, acute renal failure, pneumonitis, myocarditis, and septic shock. However, there are no documented cases of scrub typhus with hypokalemia. In this report, we present a case of scrub typhus with hypokalemia and multiple organ failure syndrome, highlighting the importance of electrolyte imbalance in patients with scrub typhus. CASE REPORT: A 59-year-old woman presented to the emergency department with abdominal pain that had been present for 1 day. On admission, the physical examination and laboratory test results indicated that the patient had renal, liver, and circulatory failure, and hypokalemia. She developed meningitis and disseminated intravascular coagulation during hospitalization. She recovered with appropriate management, and was discharged on day 17. CONCLUSION: This report highlights the potential for atypical presentations of scrub typhus, including a previously undocumented association with hypokalemia. Although the contribution of hypokalemia to the patient's clinical course remains uncertain, this case underscores the importance of considering electrolyte imbalance in the management of patients with scrub typhus. Further research is warranted to better understand the relationship between scrub typhus and electrolyte imbalance.

Endoplasmic Reticulum-Targeting Self-Assembly Nanosheets Promote Autophagy and Regulate Immunosuppressive Tumor Microenvironment for Efficient Photodynamic Immunotherapy.

The poor efficiency and low immunogenicity of photodynamic therapy (PDT), and the immunosuppressive tumor microenvironment (ITM) lead to tumor recurrence and metastasis. In this work, TCPP-TER-Zn@RSV nanosheets (TZR NSs) that co-assembled from the endoplasmic reticulum (ER)-targeting photosensitizer TCPP-TER-Zn nanosheets (TZ NSs for short) and the autophagy promoting and indoleamine-(2, 3)-dioxygenase (IDO) inhibitor-like resveratrol (RSV) are fabricated to enhance antitumor PDT. TZR NSs exhibit improved therapeutic efficiency and amplified immunogenic cancer cell death (ICD) by ER targeting PDT and ER autophagy promotion. TZR NSs reversed the ITM with an increase of CD8+ T cells and reduce of immunosuppressive Foxp3 regulatory T cells, which effectively burst antitumor immunity thus clearing residual tumor cells. The ER-targeting TZR NSs developed in this paper presents a simple but valuable reference for high-efficiency tumor photodynamic immunotherapy.

Metformin adverse event profile: a pharmacovigilance study based on the FDA Adverse Event Reporting System (FAERS) from 2004 to 2022.

BACKGROUND: Metformin has the potential for treating numerous diseases, but there are still many unrecognized and unreported adverse events (AEs). METHODS: We selected data from the United States FDA Adverse Event Reporting System (FAERS) database from the first quarter (Q1) of 2004 to the fourth quarter (Q4) of 2022 for disproportionality analysis to assess the association between metformin and related adverse events. RESULTS: In this study 10,500,295 case reports were collected from the FAERS database, of which 56,674 adverse events related to metformin were reported. A total of 643 preferred terms (PTs) and 27 system organ classes (SOCs) that were significant disproportionality conforming to the four algorithms simultaneously were included. The SOCs included metabolic and nutritional disorders (p = 0.00E + 00), gastrointestinal disorders (p = 0.00E + 00) and others. PT levels were screened for adverse drug reaction (ADR) signals such as acute pancreatitis (p = 0.00E + 00), melas syndrome, pemphigoid (p = 0.00E + 00), skin eruption (p = 0.00E + 00) and drug exposure during pregnancy (p = 0.00E + 00). CONCLUSION: Most of our results were consistent with the specification, but some new signals of adverse reactions such as acute pancreatitis were not included. Therefore, further studies are needed to validate unlabeled adverse reactions and provide important support for clinical monitoring and risk identification of metformin.

Molecular mechanism of the NOS/NOX regulation of antibacterial activity in Eriocheir sinensis.

To elucidate the role of nitric oxide synthase (NOS), which produces the free radical nitric oxide (NO), and nicotinamide adenine dinucleotide phosphate oxidase (NOX), which produces the superoxide anion (O2-), in the innate immunity of Eriocheir sinensis, the full lengths of the NOS and NOX genes were cloned via rapid amplification of the cDNA ends and then expressed in the prokaryotic form to obtain the recombinant proteins, NOS-HIS and NOX-HIS. Through bacterial binding and stimulation experiments, the molecular mechanisms of NOS and NOX in the innate immunity of E. sinensis were explored. Based on the results, NOS and NOX were 5900 bp and 4504 bp long, respectively, and were evolutionarily conserved. Quantitative real-time PCR revealed that NOS and NOX were expressed in all studied tissues, and both were expressed in the highest amounts in hemocytes. NOS-HIS and NOX-HIS could bind to bacteria with different binding powers; their binding ability to gram-positive bacteria was higher than that of binding to gram-negative bacteria. After stimulation with Aeromonas hydrophila, NOS expression was significantly up-regulated at 3, 6, and 48 h, and NOX expression was significantly down-regulated at 3, 12, 24, and 48 h. After bacterial stimulation, the NOS enzyme activity in the serum of E. sinensis was also significantly up-regulated at 6 and 48 h, and the NOX enzyme activity was significantly down-regulated at 12 and 48 h, aligning with the gene expression trend. Moreover, the related free radical molecules, NO, O2-, and H2O2, tended to decrease after bacterial stimulation. Overall, the gene expression and enzyme activity of NOS and NOX had been changed respectively, and the contents of a series of free radical molecules (NO, O2- and H2O2) were induced in E. sinensis after bacterial stimulation, which then exert antibacterial immunity.

Inhibition of autophagy enhances the anticancer effect of Schisandrin B on head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is among the most common malignant tumors worldwide and has a poor prognosis. Autophagy regulation has been proposed as a possible treatment option for HNSCC. Schisandrin B (Sch B) exerts anticancer effects by regulating apoptosis and autophagy, but the anticancer effect of Sch B in HNSCC remains unclear. This study aimed to investigate the effects of Sch B on human Cal27 HNSCC cells and to further reveal its potential regulatory mechanisms. The anticancer effect of Sch B was evaluated in vitro by flow cytometry, clonogenic assays, and Western blot analysis. The regulatory mechanism of Sch B-induced apoptosis and autophagy was further explored by polymerase chain reaction, luciferase assay, and reactive oxygen species (ROS) detection. The results showed that Sch B significantly induced apoptosis and autophagy in Cal27 cells and that inhibition of autophagy enhanced the apoptotic effect of Sch B on Cal27 cells. Additionally, Sch B-activated autophagy in Cal27 cells was dependent on the nuclear factor-kappa B (NF-κB) pathway, and ROS acted as a regulator of the NF-B pathway. N-acetylcysteine, a scavenger of ROS, inhibited Sch B-dependent autophagy via the NF-κB pathway. Based on the results, Sch B is a potential therapeutic agent for HNSCC and activates the NF-κB pathway by increasing ROS production, which subsequently promotes autophagy in HNSCC cells. Therefore, the strategy of enhancing the anticancer effect of Sch B by inhibiting autophagy deserves further attention.

Case report of scrub typhus complicated by hypokalemia and multiple organ dysfunction syndrome

ABSTRACT CONTEXT: Scrub typhus, caused by Orientia tsutsugamushi, has a wide range of clinical manifestations, including meningoencephalitis, acute renal failure, pneumonitis, myocarditis, and septic shock. However, there are no documented cases of scrub typhus with hypokalemia. In this report, we present a case of scrub typhus with hypokalemia and multiple organ failure syndrome, highlighting the importance of electrolyte imbalance in patients with scrub typhus. CASE REPORT: A 59-year-old woman presented to the emergency department with abdominal pain that had been present for 1 day. On admission, the physical examination and laboratory test results indicated that the patient had renal, liver, and circulatory failure, and hypokalemia. She developed meningitis and disseminated intravascular coagulation during hospitalization. She recovered with appropriate management, and was discharged on day 17. CONCLUSION: This report highlights the potential for atypical presentations of scrub typhus, including a previously undocumented association with hypokalemia. Although the contribution of hypokalemia to the patient's clinical course remains uncertain, this case underscores the importance of considering electrolyte imbalance in the management of patients with scrub typhus. Further research is warranted to better understand the relationship between scrub typhus and electrolyte imbalance.

Esketamine Combined with Propofol TCI versus Propofol TCI for Deep Sedation during Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: A Prospective, Randomized, and Controlled Trial.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an invasive procedure that required deep sedation to suppress coughing and body movements. Deep sedation, on the other hand, has been shown to cause respiratory and circulatory depression, especially when the airway is shared with the endoscopist. Esketamine is a novel sedative and analgesic with little respiratory inhibition that appears to be an appropriate adjuvant in propofol sedation for EBUS-TBNA. We compared the efficacy and safety of esketamine combined with propofol target-controlled infusion (TCI) and propofol TCI for deep sedation in EBUS-TBNA. Methods: The study included 135 patients with ASA II-III undergoing EBUS-TBNA. They were randomly divided into two groups (group E and group P). Both groups received midazolam (0.01-0.03 mg/kg) and oxycodone (0.07-0.08 mg/kg). Then, patients in group E received 0.3 mg/kg esketamine, propofol TCI, and 0.2 mg·kg-1·h-1 esketamine for sedative maintenance. Patients in group P received only propofol TCI. The primary outcome was the dose of 1% lidocaine administrated by the endoscopist and the times of lidocaine sprays. Secondary outcome indicators were cough score, propofol dosage, patient satisfaction, endoscopist satisfaction, the incidence of sedation-related adverse effects and side effects, and recovery time. Results: Patients in group E were given significantly less lidocaine (4.36 ml/h (2.67-6.00) vs 6.00 ml/h (4.36-7.20), P < 0.001) and less spraying frequency (2.18 times/h (1.33-3.00) vs 3.00 times/h (2.18-3.60), P < 0.001) than group P. There was a statistically significant difference in cough score between the two groups (group E 2 (0-4) vs group P 3 (2-4), P=0.03). Also, mean arterial pressure (MAP) was higher in group E in the 30th min (T5, 84.10 ± 12.91 mmHg versus 79.04 ± 10.01 mmHg, P=0.012) and 40th min (T6, 87.72 ± 15.55 mmHg versus 82.14 ± 10.51 mmHg, P=0.026). There were no significant differences between the two groups in terms of sedation-related adverse events and side effects, recovery time, endoscopist satisfaction, and patient satisfaction. Conclusions: In patients with ASA II-III, esketamine as an adjuvant in combination with propofol TCI deep sedation for EBUS-TBNA can improve the sedation effect, reduce coughing reaction during the procedure, and obtain more stable blood pressure. No reduction in the occurrence of sedation-related side effects was observed. This trial is registered with ChiCTR2200061124.

Risk Factors Analysis of Phantom Limb Pain in Amputees with Malignant Tumors.

Purpose: Postamputation neuropathic pain is a common disease in patients with malignant tumor amputation, seriously affecting amputees' quality of life and mental health. The objective of this study was to identify independent risk factors for phantom limb pain in patients with tumor amputation and to construct a risk prediction model. Methods: Patients who underwent amputation due to malignant tumors from 2013 to 2023 were retrospectively analyzed and divided into phantom limb pain group and non-phantom limb pain group. To determine which preoperative factors would affect the occurrence of phantom limb pain, we searched for candidate factors by univariate analysis and used multivariate logistic regression analysis to identify independent factors and construct a predictive model. The receiver operating characteristic curve (ROC) was drawn to further evaluate the accuracy of the prediction model in evaluating the phantom limb pain after amputation of bone and soft tissue tumors. Results: Multivariate analysis showed that age (OR, 1.054; 95% CI, 1.027 to 1.080), preoperative pain (OR, 5.773; 95% CI, 2.362 to 14.104), number of surgeries (OR, 3.425; 95% CI, 1.505 to 7.795), amputation site (OR, 5.848; 95% CI, 1.837 to 18.620), amputation level (OR, 8.031; 95% CI, 2.491 to 25.888) were independent risk factors for phantom limb pain for bone and soft tissue tumors. The the area under the curve (AUC) of this model was 0.834. Conclusion: Risk factors for postoperative phantom limb pain were the site of amputation, proximal amputation, preoperative pain, multiple amputations, and older age. These factors will help surgeons to individualize and stratify phantom limb pain and help patients with risk counseling. In particular, an informed clinical decision targeting those modifiable factors can be considered when needed.

Lunasin ameliorates glucose utilization in C2C12 myotubes and metabolites profile in diet-induced obese mice benefiting metabolic disorders.

AIMS: Obesity is the main cause of low-grade inflammation and oxidation, resulting in insulin resistance. This study aimed to investigate the effects of a seed peptide lunasin on glucose utilization in C2C12 myotubes and the metabolite profiles in obese mice. MAIN METHODS: C2C12 myotubes were challenged by palmitic acid (PA) to mimic the obese microenvironment and inflammation, cell vitality, and glucose utilization were determined. C57BL6/j mice were divided into low-fat diet (LF), high-fat diet (HF), and HF with intraperitoneally injected lunasin (HFL) groups. Glucose intolerance and metabolite profiles of the tissues were analyzed. KEY FINDINGS: In vitro, C2C12 myotubes treated with lunasin showed decreased proinflammatory cytokines and increased cell vitality under palmitic acid conditions. Lunasin improved glucose uptake and glucose transporter 4 expression by activating insulin receptor substrate-1 and AKT phosphorylation. Next-generation sequencing revealed that lunasin regulates genes expression by promoting insulin secretion and decreasing oxidative stress. In vivo, HF mice showed increased tricarboxylic acid cycle and uric acid metabolites but decreased bile acids metabolites and specific amino acids. Lunasin intervention improved glucose intolerance and modulated metabolites associated with increased insulin sensitivity and decreased metabolic disorders. SIGNIFICANCE: This study is the first to reveal that lunasin is a promising regulator of anti-inflammation, anti-oxidation, and glucose utilization in myotubes and ameliorating glucose uptake and metabolite profiles in obese mice, contributing to glucose homeostasis and benefiting metabolic disorders.

P66Shc is increased in peripheral blood mononuclear cells of the patients with obstructive sleep apnea.

Objective: Obstructive sleep apnea (OSA) is characterized by nocturnal intermittent hypoxemia and linked to oxidative stress. Evidence demonstrated that p66Shc plays a key role in regulating oxidative stress. This study aimed to investigate the expression of p66Shc in peripheral blood mononuclear cells (PBMCs) of patients with OSA and the association with polysomnographic parameters. Methods: Fifty-four OSA subjects and 19 no OSA controls were enrolled in this study. All the subjects underwent standard polysomnography. P66Shc mRNA and protein levels in the PBMCs were detected by quantitative real-time polymerase chain reaction and western blotting. Plasma 3-nitrotyrosine (3-NT), oxidized low density lipoprotein (oxLDL), and advanced oxidation protein products (AOPP) were measured by ELISA method. Results: P66Shc mRNA and protein levels in PBMCs were significantly higher in OSA patients than in controls. P66Shc mRNA was positively correlated with plasma 3-NT, oxLDL, AOPP, hypopnea index (AHI), oxygen desaturation index (ODI), percentage of total sleep time with oxygen saturation (SaO2) below 90% (CT90), epworth sleepiness scale (ESS) and lymphocytes; negatively correlated with lowest SaO2 (LSaO2) and mean SaO2 (MSaO2). Further multivariate linear regression analysis showed that p66Shc mRNA levels were independently associated with AHI, MSaO2 and CT90. Conclusions: Oxidative stress regulator p66Shc may play a role in the pathophysiology of OSA and might serve as a potential biomarker for this disease.

Age-specific effects on adverse pregnancy outcomes vary by maternal characteristics: a population-based retrospective study in Xiamen, China.

BACKGROUND: Advanced maternal age (AMA; ≥35 years) is considered to be a major risk factor for adverse pregnancy outcomes. Along with the global trend of delayed childbearing, and in particular, the implementation of China's second and third-child policy leading to a dramatic increase of AMA in recent years, the association between maternal age and pregnancy outcomes requires more investigation. METHODS: A population-based retrospective study was performed. Data were derived from the Medical Birth Registry of Xiamen from 2011 to 2018. Univariate and multivariate logistic regression was used to evaluate the effects of maternal age on pregnancy outcomes. RESULTS: A total of 63,137 women categorized into different age groups (< 25 years, 25-29 years, 30-34 years, and ≥ 35 years) were included in this study. Compared with the mothers aged 25-29 years, the univariate regression analysis showed that mothers aged < 25 years had lower risks of gestational diabetes mellitus (GDM) and cesarean. AMA was associated with higher risks of GDM, hypertension, cesarean, preterm birth, low-birth weight (LBW), large-for-gestational-age (LGA), macrosomia, and stillbirth (all P < 0.01). After adjustment for potential confounding factors, increased risks of GDM, hypertension, cesarean, preterm birth, and LBW remained significantly associated with AMA (all P < 0.05), whereas AMA mothers showed a lower risk of macrosomia than their younger counterparts. Additionally, no significant differences were detected in terms of Apgar score < 7. CONCLUSION: AMA was associated with adverse pregnancy outcomes including increased risks of GDM, hypertension, cesarean, preterm birth, and LBW. This study confirmed the relationship between AMA and certain adverse maternal and fetal outcomes and emphasizes the necessity for women to be cautious about the age at which they become pregnant.