Tectorigenin inhibits inflammatory responses in murine inflammatory bowel disease and LPS-stimulated macrophages via inactivating MAPK signaling pathway.

BACKGROUND: Considering the antihepatitis effects of Tectorigenin (TEC), and the same adenosine mitogen-activated protein kinase (MAPK) pathway in both hepatitis and inflammatory bowel disease (IBD) models, exploring the role of TEC in IBD is contributive to develop a new treatment strategy against IBD. METHODS: The IBD mouse model was constructed by feeding with dextran sodium sulfate (DSS) and injection of TEC. Afterward, the mouse body weight, colon length, and disease activity index (DAI) were tested to assess the enteritis level. Mouse intestine lesions were detected by hematoxylin and eosin staining. Murine macrophages underwent lipopolysaccharide (LPS) induction to establish an inflammation model. Cell viability was determined by cell counting kit-8 assay. Enzyme-linked immunosorbent assay was performed to measure interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) levels. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions were quantified via quantitative reverse transcription polymerase chain reaction. Levels of MAPK pathway-related proteins (p-P38, P38, p-Jun N-terminal kinase (JNK), JNK, signal-regulated kinase (ERK), p-ERK), COX-2 and iNOS were quantitated by Western blot. RESULTS: TEC improved the inflammatory response through ameliorating weight loss, shortening colon, and increasing DAI score in IBD mouse. Expressions of intestinal inflammatory factors (IL-6, TNF-α, iNOS and COX-2) and MAPK pathway-related proteins (p-P38, p-JNK, and p-ERK) were increased both in DSS-induced mouse intestinal tissue, but TEC inhibited expressions of inflammatory factors. The same increased trend was identified in LPS-induced macrophages, but TEC improved macrophage inflammation, as evidenced by downregulation of inflammatory factors. CONCLUSION: TEC mitigates IBD and LPS-induced macrophage inflammation in mice via inhibiting MAPK signaling pathway.

Proteomic analysis reveals potential therapeutic targets for childhood asthma through Mendelian randomization.

BACKGROUND: Asthma is the most common chronic disease among children and poses a significant threat to their health. This study aims to assess the relationship between various plasma proteins and childhood asthma, thereby identifying potential therapeutic targets. METHODS: Based on publicly available genome-wide association study summary statistics, we employed a two-sample Mendelian randomization (MR) approach to elucidate the causal relationship between plasma proteins and asthma. Mediation analysis was then conducted to evaluate the indirect influence of plasma proteins on childhood asthma mediated through risk factors. Comprehensive analysis was also conducted to explore the association between plasma proteins and various phenotypes using the UK Biobank dataset. RESULTS: MR analysis uncovered a causal relationship between 10 plasma proteins and childhood asthma. Elevated levels of seven proteins (TLR4, UBP25, CBR1, Rac GTPase-activating protein 1 [RGAP1], IL-21, MICB, and PDE4D) and decreased levels of three proteins (GSTO1, LIRB4 and PIGF) were associated with an increased risk of childhood asthma. Our findings further validated the connections between reported risk factors (body mass index, mood swings, hay fever or allergic rhinitis, and eczema or dermatitis) and childhood asthma. Mediation analysis revealed the influence of proteins on childhood asthma outcomes through risk factors. Furthermore, the MR analysis identified 73 plasma proteins that exhibited causal associations with at least one risk factor for childhood asthma. Among them, RGAP1 mediates a significant proportion (25.10%) of the risk of childhood asthma through eczema or dermatitis. Finally, a phenotype-wide association study based on these 10 proteins and 1403 diseases provided novel associations between these biomarkers and multiple phenotypes. CONCLUSION: Our study comprehensively investigated the causal relationship between plasma proteins and childhood asthma, providing novel insights into potential therapeutic targets.

Single-cell transcriptome reveals highly complement activated microglia cells in association with pediatric tuberculous meningitis.

Background: Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB) causing high mortality and disability. TBM arises due to immune dysregulation, but the underlying immune mechanisms are unclear. Methods: We performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells isolated from children (n=6) with TBM using 10 xGenomics platform. We used unsupervised clustering of cells and cluster visualization based on the gene expression profiles, and validated the protein and cytokines by ELISA analysis. Results: We revealed for the first time 33 monocyte populations across the CSF cells and PBMCs of children with TBM. Within these populations, we saw that CD4_C04 cells with Th17 and Th1 phenotypes and Macro_C01 cells with a microglia phenotype, were enriched in the CSF. Lineage tracking analysis of monocyte populations revealed myeloid cell populations, as well as subsets of CD4 and CD8 T-cell populations with distinct effector functions. Importantly, we discovered that complement-activated microglial Macro_C01 cells are associated with a neuroinflammatory response that leads to persistent meningitis. Consistently, we saw an increase in complement protein (C1Q), inflammatory markers (CRP) and inflammatory factor (TNF-α and IL-6) in CSF cells but not blood. Finally, we inferred that Macro_C01 cells recruit CD4_C04 cells through CXCL16/CXCR6. Discussion: We proposed that the microglial Macro_C01 subset activates complement and interacts with the CD4_C04 cell subset to amplify inflammatory signals, which could potentially contribute to augment inflammatory signals, resulting in hyperinflammation and an immune response elicited by Mtb-infected tissues.

Superhydrophobic/ superoleophilic polystyrene-based porous material with superelasticity for highly efficient and continuous oil/water separation in harsh environments.

Three-dimensional separation materials with robust physical/chemical stability have great demand for effective and continuous separation of immiscible oil/water mixtures and water-in-oil emulsions, resulting from chemical leakages and discharge of industrial oily wastewaters. Herein, a superelastic polystyrene-based porous material with superhydrophobicity/superoleophilicity was designed and prepared by high internal phase emulsion polymerization to meet the aforementioned requirements. A flexible and hydrophobic aminopropyl terminated polydimethylsiloxane (NH2-PDMS-NH2) segment was introduced into the rigid styrene-divinylbenzene copolymer through 1, 4-conjugate addition reaction with trimethylolpropane triacrylate. The addition of NH2-PDMS-NH2 simultaneously improved the mechanical and hydrophobic properties of the porous material (the water contact angle from 141.2° to 152.2°). The material exhibited outstanding reversible compressibility (80% strain, even in liquid N2 environments) and superhydrophobic stability, even after being repeatedly compressed 100 times, water contact angle still remained above 150°. Meanwhile, the as-prepared material had outstanding hydrophobic stability in corrosive solutions (strong acidic, alkaline, high-salty, and even strong polar solvent), presence of mechanical interference, strong UV radiations, and high/low temperature environments. More importantly, the material could continuously and efficiently separate immiscible oil/water mixture and water-in-oil emulsions under the above conditions, showing huge potential for the large-scale remediation of complex oily wastewaters.

Hydromassage of macular hole edges for large and persistent full-thickness macular holes.

AIM: To introduce the macular hole (MH) hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH. METHODS: This retrospective observational case series comprised 16 consecutive patients (17 eyes) diagnosed with MH. Inclusion criteria involved a hole aperture diameter larger than 600 µm or the presence of an unclosed MH larger than 600 µm following the previous vitrectomy. Standard MH repair procedures were administered in all cases, involving the manipulation and aspiration of the hole margin through the application of water flow with a soft-tip flute needle. A comprehensive assessment was conducted for each case before and after surgery, and optical coherence tomography (OCT) images were captured at every follow-up point. RESULTS: The mean preoperative aperture diameter was 747±156 µm (range 611-1180 µm), with a mean base diameter of 1390±435 µm (range 578-2220 µm). Following surgery, all cases achieved complete anatomical closure of MH, with 13 cases (76.5%) exhibiting type 1 closure and 4 cases (23.5%) demonstrating type 2 closure. No significant differences were observed in the preoperative OCT variables between the two closure types. Eyes with type 1 closure showed a significantly improved visual acuity (0.70±0.10, range 0.50-0.80) compared to those with type 2 closure (0.90±0.12, range 0.80-1.00, P=0.014). CONCLUSION: The MH hydromassage technique demonstrates promising results, achieving acceptable closure rates in cases of large or persistent MH. This technique may serve as an effective adjunctive maneuver during challenging MH surgery.

Endotherapy for the proximal migration of pancreatic stents: A systematic review.

OBJECTIVES: Proximal migration is one of the complications after pancreatic duct stenting. This study aimed to determine the incidence of proximal migration and to analyze the rescue methods. METHODS: A search was performed in MEDLINE/EMBASE database. The literatures included were reviewed and analyzed. Retrieval tools were classified into 3 classes: Class A works by indirectly contacting the outer surface of the stent. Class B works by directly contacting the outer surface. Class C works by directly contacting the inner surface. RESULTS: 416 literatures were retrieved from 1983 to 2021. 15 literatures were included. The incidence of proximal migration of pancreatic stents was 4.7% (106/2246). The success rate of endotherapy was 86.6% (214/247), and the surgical conversion rate of it was 9.3%. Among the 214 cases in which the displaced stents were successfully removed under endoscopy, 49 cases (22.9%) used Class A methods, 154 cases (72.0%) used Class B methods and 11 cases (5.1%) used Class C methods. The overall rate of postoperative complication was 12.1%, including postprocedure pancreatitis (9.1%, 18/247), followed by bleeding (1.5%), perforation (1.0%) and biliary infection (0.5%). CONCLUSIONS: Endoscopy is an effective method for the treatment of proximal displacement of pancreatic stents with acceptable complication rate.

Application of Computed Tomography Angiography in Preoperative Diagnosis of Coarctation of Aorta and Evaluation of Aortic Dilatation in Infants.

OBJECTIVE: To evaluate the occurrence of aortic dilatation and its associated predictors with coarctation of the aorta (CoA) in infants using multi-slice computed tomography (MSCT). METHODS: The clinical data of 47 infantile patients with CoA diagnosed by MSCT and 28 infantile patients with simple ventricular septal defect were analyzed retrospectively. Aortic diameters were measured at six different levels, and aortic sizes were compared by z score. The coarctation site-diaphragm ratio was used to describe the degree of narrowing. Relevant clinical data were collated and analyzed. RESULTS: The dilation rate and z score of the ascending aorta in the severe CoA group were significantly higher than those in the mild CoA group (11 [52.38%] vs. 21 [80.77%], P=0.038 and 2.00 ± 0.48 vs. 2.36 ± 0.43, P=0.010). Pearson's correlation analysis found that the z score of the ascending aorta was negatively correlated with the coarctation site-diaphragm ratio value (r=-0.410, P=0.004). A logistic retrospective analysis found that an increased degree of coarctation was an independent predictor of aortic dilatation (adjusted odds ratio 0.002; 95% confidence interval 0.00-0.819; P=0.043). The z score of the ascending aorta in the severe CoA group was significantly higher than that in the ventricular septal defect group (P<0.05). CONCLUSION: Most infants with CoA can also have significant dilatation of the ascending aorta, and the degree of this dilatation is related to the degree of coarctation. Assessment of aortic diameter and related malformations by MSCT can predict the risk of aortic dilatation in infants with CoA.

Research progress on the role and mechanism of Sirtuin family in doxorubicin cardiotoxicity.

BACKGROUND: Doxorubicin (DOX) is a widely utilized anthracycline chemotherapy drug in cancer treatment, yet its efficacy is hindered by both short-term and long-term cardiotoxicity. Although oxidative stress, inflammation and mitochondrial dysfunction are established factors in DOX-induced cardiotoxicity, the precise molecular pathways remain elusive. Further exploration of the pathogenesis and identification of novel molecular targets are imperative. Recent studies have implicated the Sirtuins family in various physiological and pathological processes, suggesting their potential in ameliorating DOX-induced cardiotoxicity. Moreover, research on Sirtuins has discovered small-molecule compounds or medicinal plants with regulatory effects, representing a notable advancement in preventing and treating DOX-induced cardiac injury. PURPOSE: In this review, we delve into the pathogenesis of DOX-induced cardiotoxicity and explore the therapeutic effects of Sirtuins in mitigating this condition, along with the associated molecular mechanisms. Furthermore, we delineate the roles and mechanisms of small-molecule regulators of Sirtuins in the prevention and treatment of DOX-induced cardiotoxicity. STUDY-DESIGN/METHODS: Data for this review were sourced from various scientific databases (such as Web of Science, PubMed and Science Direct) up to March 2024. Search terms included "Sirtuins," "DOX-induced cardiotoxicity," "DOX," "Sirtuins regulators," "histone deacetylation," among others, as well as several combinations thereof. RESULTS: Members of the Sirtuins family regulate both the onset and progression of DOX-induced cardiotoxicity through anti-inflammatory, antioxidative stress and anti-apoptotic mechanisms, as well as by maintaining mitochondrial stability. Moreover, natural plant-derived active compounds such as Resveratrol (RES), curcumin, berberine, along with synthetic small-molecule compounds like EX527, modulate the expression and activity of Sirtuins. CONCLUSION: The therapeutic role of the Sirtuins family in mitigating DOX-induced cardiotoxicity represents a potential molecular target. However, further research is urgently needed to elucidate the relevant molecular mechanisms and to assess the safety and biological activity of Sirtuins regulators. This review offers an in-depth understanding of the therapeutic role of the Sirtuins family in mitigating DOX-induced cardiotoxicity, providing a preliminary basis for the clinical application of Sirtuins regulators in this condition.

Naringenin inhibits APAP-induced acute liver injury through activating PPARA-dependent signaling pathway.

Acute liver injury (ALI) refers to the damage to the liver cells of patients due to drugs, food, and diseases. In this work, we used a network pharmacology approach to analyze the relevant targets and pathways of the active ingredients in Citri Reticulatae Pericarpium (CRP) for the treatment of ALI and conducted systematic validation through in vivo and in vitro experiments. The network pharmacologic results predicted that naringenin (NIN) was the main active component of CRP in the treatment of ALI. GO functional annotation and KEGG pathway enrichment showed that its mechanism may be related to the regulation of PPARA signaling pathway, PPARG signaling pathway, AKT1 signaling pathway, MAPK3 signaling pathway and other signaling pathways. The results of in vivo experiments showed that (NIN) could reduce the liver lesions, liver adipose lesions, hepatocyte injury and apoptosis in mice with APAP-induced ALI, and reduce the oxidative stress damage of mouse liver cells and the inflammation-related factors to regulate ALI. In vitro experiments showed that NIN could inhibit the proliferation, oxidative stress and inflammation of APAP-induced LO2 cells, promote APAP-induced apoptosis of LO2 cells, and regulate the expression of apoptotic genes in acute liver injury. Further studies showed that NIN inhibited APAP-induced ALI mainly by regulating the PPARA-dependent signaling pathway. In conclusion, this study provides a preliminary theoretical basis for the screening of active compounds in CRP for the prevention and treatment of ALI.

Functional screening of the Arabidopsis 2C protein phosphatases family identifies PP2C15 as a negative regulator of plant immunity by targeting BRI1-associated receptor kinase 1.

Genetic engineering using negative regulators of plant immunity has the potential to provide a huge impetus in agricultural biotechnology to achieve a higher degree of disease resistance without reducing yield. Type 2C protein phosphatases (PP2Cs) represent the largest group of protein phosphatases in plants, with a high potential for negative regulatory functions by blocking the transmission of defence signals through dephosphorylation. Here, we established a PP2C functional protoplast screen using pFRK1::luciferase as a reporter and found that 14 of 56 PP2Cs significantly inhibited the immune response induced by flg22. To verify the reliability of the system, a previously reported MAPK3/4/6-interacting protein phosphatase, PP2C5, was used; it was confirmed to be a negative regulator of PAMP-triggered immunity (PTI). We further identified PP2C15 as an interacting partner of BRI1-associated receptor kinase 1 (BAK1), which is the most well-known co-receptor of plasma membrane-localized pattern recognition receptors (PRRs), and a central component of PTI. PP2C15 dephosphorylates BAK1 and negatively regulates BAK1-mediated PTI responses such as MAPK3/4/6 activation, defence gene expression, reactive oxygen species bursts, stomatal immunity, callose deposition, and pathogen resistance. Although plant growth and 1000-seed weight of pp2c15 mutants were reduced compared to those of wild-type plants, pp2c5 mutants did not show any adverse effects. Thus, our findings strengthen the understanding of the mechanism by which PP2C family members negatively regulate plant immunity at multiple levels and indicate a possible approach to enhance plant resistance by eliminating specific PP2Cs without affecting plant growth and yield.

Alkaloids from Zanthoxylum nitidum and their anti-proliferative activity against A549 cells by regulating the EGFR/AKT/mTOR pathway.

Zanthoxylum nitidum is frequently used as a traditional Chinese medicine and food supplement. Our previous study revealed that its constituent compounds were able to inhibit cancer cell proliferation. In our continuous exploration of bioactive compounds in Z. nitidum, we isolated ten alkaloids (1-10), including one new natural compound (1), and nine known alkaloids (2-10), from an ethanolic extract of the whole plant. The chemical structures were elucidated based on a combination of comprehensive NMR and HRESIMS analyses. Compounds 5, 8 and 10 exhibited significant antiproliferative effects against A549 cancer cell lines. We further elucidated the underlying molecular mechanisms of the antiproliferative activity of compound 8 in A549 human lung cancer cells. Compound 8 was found to induce cell cycle arrest in the G0/G1 phase via p53 activation and CDK4/6 suppression. Compound 8 also effectively inhibited cell migration through the modulation of the epithelial-mesenchymal transition (EMT), as indicated by the expression of biomarkers, such as N-cadherin downregulation and E-cadherin upregulation. Compound 8 significantly suppressed the activation of the EGFR/AKT/mTOR signalling pathway in A549 cells. These results indicate that alkaloid 8 from Z. nitidum has potential to be a lead antiproliferative compound in cancer cells.

Mendelian randomization and transcriptome analysis identified immune-related biomarkers for osteoarthritis.

Background: The immune microenvironment assumes a significant role in the pathogenesis of osteoarthritis (OA). However, the current biomarkers for the diagnosis and treatment of OA are not satisfactory. Our study aims to identify new OA immune-related biomarkers to direct the prevention and treatment of OA using multi-omics data. Methods: The discovery dataset integrated the GSE89408 and GSE143514 datasets to identify biomarkers that were significantly associated with the OA immune microenvironment through multiple machine learning methods and weighted gene co-expression network analysis (WGCNA). The identified signature genes were confirmed using two independent validation datasets. We also performed a two-sample mendelian randomization (MR) study to generate causal relationships between biomarkers and OA using OA genome-wide association study (GWAS) summary data (cases n = 24,955, controls n = 378,169). Inverse-variance weighting (IVW) method was used as the main method of causal estimates. Sensitivity analyses were performed to assess the robustness and reliability of the IVW results. Results: Three signature genes (FCER1G, HLA-DMB, and HHLA-DPA1) associated with the OA immune microenvironment were identified as having good diagnostic performances, which can be used as biomarkers. MR results showed increased levels of FCER1G (OR = 1.118, 95% CI 1.031-1.212, P = 0.041), HLA-DMB (OR = 1.057, 95% CI 1.045 -1.069, P = 1.11E-21) and HLA-DPA1 (OR = 1.030, 95% CI 1.005-1.056, P = 0.017) were causally and positively associated with the risk of developing OA. Conclusion: The present study identified the 3 potential immune-related biomarkers for OA, providing new perspectives for the prevention and treatment of OA. The MR study provides genetic support for the causal effects of the 3 biomarkers with OA and may provide new insights into the molecular mechanisms leading to the development of OA.

Experimental Validation of Comprehensive Calculation for High-Resolution Linear MALDI-TOF Mass Spectrometry.

This work discusses the effectiveness of the previously developed comprehensive calculation model to optimize linear MALDI-TOF mass spectrometers. The model couples space- and velocity-focusing to precisely analyze the flight-time distribution of ions and predict optimal experimental parameters for the highest mass resolving power. Experimental validation was conducted using a laboratory-made instrument to analyze CsI3 and angiotensin I ions in low to medium m/z range. The results indicate that the predicted optimal extraction voltage and delay were reasonably accurate and effective. In the low m/z range, the peak width obtained using optimal parameters reached the sub nanosecond range, corresponding to a mass resolving power of 10 000-17 000, or 20 000-34 000 if shot-to-shot random fluctuations were minimized by the dynamic data correction method. The observed optimal mass resolving power in the current experiment is 4.8-7.8 times that of commercial instruments. Practical limitations resulting in the gap between the observed and theoretical ultimate mass resolving power are discussed.

Enhancement of hepatoprotective activity of limonin from citrus seeds against acetaminophen-induced liver injury by HSCCC purification and liposomal encapsulation.

Limonin is a natural tetracyclic triterpenoid compound in citrus seeds that presents hepatoprotective effects but is often discarded as agricultural waste because of its low content and low solubility. Herein, limonin with high purity (98.11%) from citrus seeds was obtained via purification by high-speed counter-current chromatography (HSCCC) and recrystallization. Limonin-loaded liposomes (Lip-LM) prepared by thin film hydration and high pressure homogenization method to enhance its solubility and hepatoprotective effect on APAP-induced liver injury (AILI). Lip-LM appeared as lipid nanoparticles under a transmission electron microscope, and showed well dispersed nano-scale size (69.04 ± 0.42 nm), high encapsulation efficiency (93.67% ± 2.51%), sustained release, fine stability. Lip-LM also exhibited significantly better hepatoprotective activity on AILI than free limonin in vivo. In summary, Lip-LM might be used as a potential hepatoprotective agent in the form of dietary supplement and provide an effective strategy to improve the potential value of citrus seeds.

Thriving at work as a mediator of the relationship between psychological resilience and the work performance of clinical nurses.

OBJECTIVE: This study aims to investigate the relationship between psychological resilience, thriving at work, and work performance among nurses, as well as analyse the mediating role of thriving at work in the relationship between psychological resilience and the work performance of nurses. The findings are intended to serve as a reference for nursing managers to design tailored work performance intervention programs. METHOD: Using convenience sampling, 308 clinical nurses were selected from a tertiary hospital in Changsha City, Hunan Province, China, from February to April 2023. The Connor-Davidson Resilience Scale (CD-RISC), the Thriving at Work Scale, and the Work Performance Scale were employed for the questionnaire survey. Pearson correlation analysis was used to explore the relationship between psychological resilience, thriving at work and work performance. The SPSS 26.0 software's 'Process' plugin was utilised for mediation effect analysis. RESULTS: Significantly positive correlations were found between psychological resilience and thriving at work (r = 0.806, P < 0.01), thriving at work and work performance (r = 0.571, P < 0.01) as well as psychological resilience and work performance (r = 0.572, P < 0.01). Psychological resilience significantly predicted work performance positively (ß = 0.558, t = 11.165, P < 0.01), and this prediction remained significant when thriving at work (the mediating variable), was introduced (ß = 0.371, t = 4.772, P < 0.01). Psychological resilience significantly predicted thriving at work positively (ß = 0.731, t = 20.779, P < 0.01), and thriving at work significantly predicted work performance positively (ß = 0.256, t = 3.105, P < 0.05). The mediating effect size of thriving at work between psychological resilience and work performance was 33.49% (P < 0.05). CONCLUSION: Thriving at work plays a partial mediating role between psychological resilience and work performance. The level of work performance among clinical nurses was relatively high. Nursing managers can enhance thriving at work by fostering psychological resilience among clinical nurses, thereby further improving their work performance to ensure high-quality and efficient nursing care.

Impact of Hypoglossal Nerve Stimulation on Consumer Sleep Technology Metrics and Patient Symptoms.

OBJECTIVES: Obstructive sleep apnea (OSA) is usually assessed at discrete and infrequent timepoints. Wearable consumer sleep technologies (CST) may allow for more granular and longitudinal assessments of OSA therapy responses and OSA-related symptoms. METHODS: In this case series, we enrolled hypoglossal nerve stimulator (HGNS) patients who had an effective treatment response for an 8-week study using a wearable CST. Participants started with "HGNS-on," were randomized to turn off HGNS therapy during either week 4 or 5 ("HGNS-off"), followed by a return to therapy, "HGNS-resume." Participants completed validated symptom questionnaires assessing sleepiness, insomnia symptoms, functional status, and overall sleep health (Satisfaction, Alertness, Timing, Efficiency, and Duration, SATED) each week. CST metrics and survey scores were compared between HGNS treatment phases. Associations between CST metrics and survey scores were assessed. RESULTS: Seven participants with a total of 304 nights of CST data showed no statistically significant changes in total sleep time (TST), wake time after sleep onset, or sleep efficiency (SE) across the study periods. During HGNS-off, survey scores indicated significantly worsened OSA-related symptom scores. Two participants had significantly higher heart rate variability (HRV) during HGNS-off (by 3.3 and 6.3 ms) when compared to HGNS active therapy periods. Amongst CST metrics, SATED scores correlated with TST (r = 0.434, p < 0.0001), HRV (r = -0.486, p < 0.0001), and SE (r = 0.320, = 0.0014). In addition, FOSQ-10 scores correlated with average HR during sleep (r = -0.489, p < 0.001). CONCLUSION: A 1-week HGNS therapy withdrawal period impacted OSA-related sleep symptoms. Sleep-related metrics measured by a wearable CST correlated with symptom scores indicating potental value in the use of CSTs for longitudinal sleep-tracking in OSA patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

The Effect of Surgical Therapy for Obstructive Sleep Apnea on Blood Pressure and Peripheral Arterial Tonometry.

OBJECTIVE: To determine the effect of upper airway surgery on cardiovascular function in patients with obstructive sleep apnea (OSA). STUDY DESIGN: A prospective, self-controlled study from 2018 to 2023. SETTING: Two academic medical centers. METHODS: Seventy-four patients underwent surgery for OSA, including: tonsillectomy, adenoidectomy, epiglottidectomy, modified uvulopalatopharyngoplasty, maxillary expansion, and maxillomandibular advancement. Twenty-four-hour ambulatory blood pressure (BP), peripheral arterial tonometry (PAT)-based home sleep study, and sleep-related patient-reported outcomes (PROs) were captured preoperatively and at 6 months postoperatively. Paired T-tests evaluated changes in outcomes after surgery. RESULTS: Forty-one patients successfully completed preoperative and postoperative assessments. Patients were generally middle-aged (43.8 ± 12.5 years), obese (BMI 33.0 ± 5.8 kg/m2), male (68%), White (71%), and had severe OSA (apnea-hypopnea index [AHI] 33.9 ± 29.5 events/h). The 4% oxygen desaturation index (ODI) decreased from 30.7 ± 27.1 to 12.2 ± 13.6 events/h (P < .01) after surgery. There was no significant difference in 24-h BP following surgery, though clinically meaningful reductions in nocturnal systolic (-1.95 [-5.34, 1.45] mmHg) and nocturnal diastolic (-2.30 [-5.11, 0.52] mmHg) blood pressure were observed. Stratified analysis showed patients undergoing skeletal surgery (n = 17) demonstrated larger average reductions compared to those undergoing soft tissue surgery in nocturnal systolic (-4.12 [-7.72, -0.51] vs -0.10 [-5.78, 5.58] mmHg) and nocturnal diastolic (-3.94 [-7.90, 0.01] vs -0.90 [-5.11, 3.31] mmHg) pressures. No meaningful changes were observed in PAT Autonomic Index (PAI) measurements. CONCLUSION: Surgical therapy for OSA did not demonstrate statistically significant improvements in 24-h BP. However, clinically meaningful reductions in nocturnal BP were observed, particularly in skeletal surgery patients, supporting the need for larger studies of cardiovascular outcomes following OSA surgery.

A New δ-Globin Gene Variant: Hb A2-Yulin [δ46(CD5)Gly→Arg,HBD: C.139G > A].

We report a new δ-chain hemoglobin (Hb) variant observed in a 5-year-old female living in Yulin, Guangxi, China. Capillary electrophoresis revealed splitting of the Hb A2 peak into two fractions (Hb A2 and Hb A2 variant), and the Hb A2 variant was also detected by high-performance liquid chromatography. However, it could not be detected using matrix-assisted laser desorption lonization-time of flight mass spectrometry. CD41-42 (-TCTT) heterozygosity was observed on the HBB gene by PCR and reverse dot-blot hybridization. Sanger sequencing showed a new transition (G > A) at codon 46 of the HBD gene, resulting in glycine changing to arginine. Based on the patient's place of residence, the new variant was named Hb A2-Yulin [δ46(CD5)Gly→Arg,HBD:c.139G > A].

Mediating effect of depressive symptoms on the relationship of chronic pain and cardiovascular diseases among Chinese population: Evidence from the CHARLS.

OBJECTIVE: Few studies have examined the direct or indirect effect of chronic pain on cardiovascular diseases (CVD) within Chinese population. The objective aimed to investigate the mediating role of depressive symptoms between chronic pain and CVD. METHODS: 6522 participants from China Health and Retirement Longitudinal Study were included in this retrospective cohort study. The main endpoint was the occurrence of CVD. Weighted multivariate logistic regression was used to assess the association between chronic pain and depressive symptoms. Distribution-of-product method was employed to examine the mediation effect of depressive symptoms. Subgroup analyses were performed. RESULTS: 219 developed CVD at the end of follow-up period. After adjusting all confounding variables, chronic pain was associated with increased risk of depressive symptoms in total population [odds ratio (OR) = 3.85, 95%confidence interval (CI): 3.35-4.42]. Among total population, there was a positive association of chronic pain and CVD [risk ratio (RR)a = 2.00, 95% CI: 1.33-3.00] (total effect). After further adjusting depressive symptoms, the association between chronic pain and CVD was significant (RRb = 1.67, 95% CI: 1.16-2.41) (direct effect). According to the distribution-of-product test, we observed a mediating effect of depressive symptoms on the relationship between chronic pain and CVD with the percentage of mediation of 32.8%. The mediating effect of depression was observed in individuals of aged45-65 years old, female participants, participants who never drinking and not have hypertension. CONCLUSION: Chronic pain was positively associated with CVD for Chinese population, and depressive symptoms was considered to mediate the association between chronic pain and CVD.

Differences and Correlations of Morphological and Hemodynamic Parameters between Anterior Circulation Bifurcation and Side-wall Aneurysms.

OBJECTIVE: The objective of this research was to explore the difference and correlation of the morphological and hemodynamic features between sidewall and bifurcation aneurysms in anterior circulation arteries, utilizing computational fluid dynamics as a tool for analysis. METHODS: In line with the designated inclusion criteria, this study covered 160 aneurysms identified in 131 patients who received treatment at Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, China, from January 2021 to September 2022. Utilizing follow-up digital subtraction angiography (DSA) data, these cases were classified into two distinct groups: the sidewall aneurysm group and the bifurcation aneurysm group. Morphological and hemodynamic parameters in the immediate preoperative period were meticulously calculated and examined in both groups using a three-dimensional DSA reconstruction model. RESULTS: No significant differences were found in the morphological or hemodynamic parameters of bifurcation aneurysms at varied locations within the anterior circulation. However, pronounced differences were identified between sidewall and bifurcation aneurysms in terms of morphological parameters such as the diameter of the parent vessel (Dvessel), inflow angle (θF), and size ratio (SR), as well as the hemodynamic parameter of inflow concentration index (ICI) (P<0.001). Notably, only the SR exhibited a significant correlation with multiple hemodynamic parameters (P<0.001), while the ICI was closely related to several morphological parameters (R>0.5, P<0.001). CONCLUSIONS: The significant differences in certain morphological and hemodynamic parameters between sidewall and bifurcation aneurysms emphasize the importance to contemplate variances in threshold values for these parameters when evaluating the risk of rupture in anterior circulation aneurysms. Whether it is a bifurcation or sidewall aneurysm, these disparities should be considered. The morphological parameter SR has the potential to be a valuable clinical tool for promptly distinguishing the distinct rupture risks associated with sidewall and bifurcation aneurysms.