Tuning Crystal Phase of Palladium-Selenium Nanowires for Enhanced Ethylene Glycol Electrocatalytic Oxidation.

Alcohol electrooxidation is pivotal for a sustainable energy economy. However, designing efficient electrocatalysts for this process is still a formidable challenge. Herein, palladium-selenium nanowires featuring distinct crystal phases: monoclinic Pd7Se2 and tetragonal Pd4.5Se for ethylene glycol electrooxidation reaction (EGOR) are synthesized. Notably, the supported monoclinic Pd7Se2 nanowires (m-Pd7Se2 NWs/C) exhibit superior EGOR activity, achieving a mass activity (MA) and specific activity (SA) of 10.4 A mgPd -1 (18.7 mA cm-2), which are 8.0 (6.7) and 10.4 (8.2) times versus the tetragonal Pd4.5Se and commercial Pd/C and surpass those reported in the literature. Furthermore, m-Pd7Se2 NWs/C displays robust catalytic activity for other alcohol electrooxidation. Comprehensive characterization and density functional theory (DFT) calculations reveal that the enhanced electrocatalytic performance is attributed to the increased formation of Pd0 on the high-index facets of the m-Pd7Se2 NWs, which lowers the energy barriers for the C─C bond dissociation in CHOHCHOH* and the CO* oxidation to CO2*. This study provides palladium-based alloy electrocatalysts exhibiting the highest mass activity reported to date for the electrooxidation of ethylene glycol, achieved through the crystalline phase engineering strategy.

Establishment and validation of a novel disulfidptosis-related immune checkpoint gene signature in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal tumors and is associated with a unfavorable prognosis. Disulfidptosis is a recently identified form of cell death mediated by disulfide bonds. Numerous studies have highlighted the significance of immune checkpoint genes (ICGs) in ccRCC. Nevertheless, the involvement of disulfidptosis-related immune checkpoint genes (DRICGs) in ccRCC remains poorly understood. METHODS: The mRNA expression profiles and clinicopathological data of ccRCC patients were obtained from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases. The associations between disulfidptosis-related genes (DRGs) and immune checkpoint genes (ICGs) were assessed to identify DRICGs. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were conducted to construct a risk signature. RESULTS: A total of 39 differentially expressed immune-related candidate genes were identified. A prognostic signature was constructed utilizing nine DRICGs (CD276, CD80, CD86, HLA-E, LAG3, PDCD1LG2, PVR, TIGIT, and TNFRSF4) and validated using GEO data. The risk model functioned as an independent prognostic indicator for ccRCC, while the associated nomogram provided a reliable scoring system for ccRCC. Gene set enrichment analysis indicated enrichment of phospholipase D, antigen processing and presentation, and ascorbate and aldarate metabolism-related signaling pathways in the high-risk group. Furthermore, the DRICGs exhibited correlations with the infiltration of various immune cells. It is noteworthy that patients with ccRCC categorized into distinct risk groups based on this model displayed varying sensitivities to potential therapeutic agents. CONCLUSIONS: The novel DRICG-based risk signature is a reliable indicator for the prognosis of ccRCC patients. Moreover, it also aids in drug selection and correlates with the tumour immune microenvironment in ccRCC.

Surgical procedures and complications in placement of totally implantable venous access port in pediatric hemophilia patients: A retrospective analysis.

This retrospective study at Beijing Children's Hospital (2020-2023) analyzed surgical procedures and complications in 24 pediatric hemophilia patients undergoing Totally Implantable Venous Access Port (TIVAP) insertion, primarily in the right jugular vein (RJV). We detailed the surgical process, including patient demographics and intraoperative imaging use. The choice of the RJV for TIVAP placement was influenced by its larger diameter and superficial anatomical position, potentially reducing risks like thrombosis and infection. Our findings support the RJV as a safer alternative for port placement in pediatric patients, aligning with current literature. Statistical analysis revealed no significant correlation between complications and baseline characteristics like weight and diagnosis type. However, the length of hospital stay and implant brand were significant risk factors for catheter or port displacement and removal. The limited patient number may introduce bias, suggesting a need for further studies with larger samples. Despite a 14.7 %-33 % complication rate and 5 port removals, the advantages of TIVAP, including reliable venous access, reduced discomfort, and treatment convenience, were evident. Most complications improved with symptomatic treatment, and there were no deaths due to port-related complications, underscoring the impact of TIVAP on improving pediatric hemophilia treatment.

Whole exome sequencing analyses reveal novel genes in telomere length and their biomedical implications.

Telomere length is a putative biomarker of aging and is associated with multiple age-related diseases. There are limited data on the landscape of rare genetic variations in telomere length. Here, we systematically characterize the rare variant associations with leukocyte telomere length (LTL) through exome-wide association study (ExWAS) among 390,231 individuals in the UK Biobank. We identified 18 robust rare-variant genes for LTL, most of which estimated effects on LTL were significant (> 0.2 standard deviation per allele). The biological functions of the rare-variant genes were associated with telomere maintenance and capping and several genes were specifically expressed in the testis. Three novel genes (ASXL1, CFAP58, and TET2) associated with LTL were identified. Phenotypic association analyses indicated significant associations of ASXL1 and TET2 with cancers, age-related diseases, blood assays, and cardiovascular traits. Survival analyses suggested that carriers of ASXL1 or TET2 variants were at increased risk for cancers; diseases of the circulatory, respiratory, and genitourinary systems; and all-cause and cause-specific deaths. The CFAP58 carriers were at elevated risk of deaths due to cancers. Collectively, the present whole exome sequencing study provides novel insights into the genetic landscape of LTL, identifying novel genes associated with LTL and their implications on human health and facilitating a better understanding of aging, thus pinpointing the genetic relevance of LTL with clonal hematopoiesis, biomedical traits, and health-related outcomes.

iLipidome: enhancing statistical power and interpretability using hidden biosynthetic interdependencies in the lipidome.

Numerous biological processes and diseases are influenced by lipid composition. Advances in lipidomics are elucidating their roles, but analyzing and interpreting lipidomics data at the systems level remain challenging. To address this, we present iLipidome, a method for analyzing lipidomics data in the context of the lipid biosynthetic network, thus accounting for the interdependence of measured lipids. iLipidome enhances statistical power, enables reliable clustering and lipid enrichment analysis, and links lipidomic changes to their genetic origins. We applied iLipidome to investigate mechanisms driving changes in cellular lipidomes following supplementation of docosahexaenoic acid (DHA) and successfully identified the genetic causes of alterations. We further demonstrated how iLipidome can disclose enzyme-substrate specificity and pinpoint prospective glioblastoma therapeutic targets. Finally, iLipidome enabled us to explore underlying mechanisms of cardiovascular disease and could guide the discovery of early lipid biomarkers. Thus, iLipidome can assist researchers studying the essence of lipidomic data and advance the field of lipid biology.

DUSP22 inhibits lung tumorigenesis by suppression of EGFR/c-Met signaling.

DUSP22, an atypical dual-specificity phosphatase enzyme, plays a significant role in regulating multiple kinase signaling pathways by dephosphorylation. Our study demonstrated that decreased DUSP22 expression is associated with shorter disease-free survival, advanced TNM (tumor, lymph nodes, and metastasis), cancer stage, and higher tumor grade in lung adenocarcinoma (LUAD) patients. Exogenous DUSP22 expression reduces the colony-forming capacity of lung cancer cells and inhibits xenograft tumor growth primarily by targeting EGFR and suppressing its activity through dephosphorylation. Knockdown of DUSP22 using shRNA enhances EGFR dependency in HCC827 lung cancer cells and increases sensitivity to gefitinib, an EGFR inhibitor. Consistently, genetic deletion of DUSP22 enhances EGFRdel (exon 19 deletion)-driven lung tumorigenesis and elevates EGFR activity. Pharmacological inhibition of DUSP22 activates EGFR, ERK1/2, and upregulates downstream PD-L1 expression. Additionally, lentiviral deletion of DUSP22 by shRNA enhances lung cancer cell migration through EGFR/c-Met and PD-L1-dependent pathways. Gefitinib, an EGFR inhibitor, mechanistically suppresses migration induced by DUSP22 deletion and inhibits c-Met activity. Furthermore, cabozantinib, a c-Met inhibitor, reduces migration and attenuates EGFR activation caused by DUSP22 deletion. Collectively, our findings support the hypothesis that loss of DUSP22 function in lung cancer cells confers a survival advantage by augmenting EGFR signaling, leading to increased activation of downstream c-Met, ERK1/2, and PD-L1 axis, ultimately contributing to the progression of advanced lung cancer.

Effect of Acoustic Environment in Wards on Postoperative Rehabilitation in Patients with Oral Cancer: A Retrospective Study.

OBJECTIVE: The increase in patient flow, replacement of medical equipment, and variations in surrounding environments induce increasingly serious acoustic environment problems in hospitals. This study aims to provide additional bases for the formulation of subsequent management plans in clinical practice by analyzing the influence of the acoustic environment in wards and the postoperative rehabilitation effect among patients with oral cancer. METHODS: The medical records of 210 patients with oral cancer undergoing surgical treatment in Jinan Stomatological Hospital from February 2020 to October 2022 were selected for retrospective analysis. Patients with the acoustic environment in wards >55 and ≤55 dB were classified as groups A and B, respectively, according to the acoustic environment in wards. The effects of the acoustic environment in wards on postoperative blood pressure, blood viscosity, and blood glucose fluctuation (BGF) were observed to further analyze their relationship. RESULTS: No significant difference was observed in indices such as preoperative systolic pressure (SP), diastolic pressure (DP), cardiac output (CO), postoperative CO, total cholesterol, and low- and high-density lipoproteins between the two groups (P > 0.05). The SP, DP, whole blood low-shear viscosity (WBLSV), whole blood middle-shear viscosity (WBMSV), whole blood high-shear viscosity (WBHSV), and BGF in group B were significantly lower than group A (P < 0.05). Correlation results showed that the total mean value of the acoustic environment in wards was positively correlated with SP, DP, WBLSV, WBMSV, WBHSV, and BGF (P < 0.05). CONCLUSION: The high acoustic environment in wards is significantly positively correlated with postoperative blood pressure, blood viscosity, and BGF in patients with oral cancer. The hospital should focus on and strengthen the management of the acoustic environment in wards, providing additional schemes to promote the postoperative recovery of patients with oral cancer.

Revealing molecular and cellular heterogeneity in hypopharyngeal carcinogenesis through single-cell RNA and TCR/BCR sequencing.

Introduction: Hypopharyngeal squamous cell carcinoma (HSCC) is one of the malignant tumors with the worst prognosis in head and neck cancers. The transformation from normal tissue through low-grade and high-grade intraepithelial neoplasia to cancerous tissue in HSCC is typically viewed as a progressive pathological sequence typical of tumorigenesis. Nonetheless, the alterations in diverse cell clusters within the tissue microenvironment (TME) throughout tumorigenesis and their impact on the development of HSCC are yet to be fully understood. Methods: We employed single-cell RNA sequencing and TCR/BCR sequencing to sequence 60,854 cells from nine tissue samples representing different stages during the progression of HSCC. This allowed us to construct dynamic transcriptomic maps of cells in diverse TME across various disease stages, and experimentally validated the key molecules within it. Results: We delineated the heterogeneity among tumor cells, immune cells (including T cells, B cells, and myeloid cells), and stromal cells (such as fibroblasts and endothelial cells) during the tumorigenesis of HSCC. We uncovered the alterations in function and state of distinct cell clusters at different stages of tumor development and identified specific clusters closely associated with the tumorigenesis of HSCC. Consequently, we discovered molecules like MAGEA3 and MMP3, pivotal for the diagnosis and treatment of HSCC. Discussion: Our research sheds light on the dynamic alterations within the TME during the tumorigenesis of HSCC, which will help to understand its mechanism of canceration, identify early diagnostic markers, and discover new therapeutic targets.

Molecular Mechanism of Yangshen Maidong Decoction in the Treatment of Chronic Heart Failure based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations.

Chronic heart failure (CHF) is a complex multifactorial clinical syndrome leading to abnormal cardiac structure and function. The severe form of this ailment is characterized by high disability, high mortality, and morbidity. Worldwide, 2-17% of patients die at first admission, of which 17-45% die within 1 year of admission and >50% within 5 years. Yangshen Maidong Decoction (YSMDD) is frequently used to treat the deficiency and pain of the heart. The specific mechanism of action of YSMDD in treating CHF, however, remains unclear. Therefore, a network pharmacology-based strategy combined with molecular docking and molecular dynamics simulations was employed to investigate the potential molecular mechanism of YSMDD against CHF. The effective components and their targets of YSMDD and related targets of CHF were predicted and screened based on the public database. The network pharmacology was used to explore the potential targets and possible pathways that involved in YSMDD treated CHF. Molecular docking and molecular dynamics simulations were performed to elucidate the binding affinity between the YSMDD and CHF targets. Screen results, 10 main active ingredients, and 6 key targets were acquired through network pharmacology analysis. Pathway enrichment analysis showed that intersectional targets associated pathways were enriched in the Prostate cancer pathway, Hepatitis B pathway, and C-type lectin receptor signaling pathways. Molecular docking and molecular dynamics simulations analysis suggested 5 critical active ingredients have high binding affinity to the 5 key targets. This research shows the multiple active components and molecular mechanisms of YSMDD in the treatment of CHF and offers resources and suggestions for future studies.

LRG1 promotes the apoptosis of pulmonary microvascular endothelial cells through KLK10 in chronic obstructive pulmonary disease.

INTRODUCTION: Cigarette smoking is one of the most important causes of COPD and could induce the apoptosis of pulmonary microvascular endothelial cells (PMVECs). The conditional knockout of LRG1 from endothelial cells reduced emphysema in mice. However, the mechanism of the deletion of LRG1 from endothelial cells rescued by cigarette smoke (CS) induced emphysema remains unclear. This research aimed to demonstrate whether LRG1 promotes the apoptosis of PMVECs through KLK10 in COPD. METHODS: Nineteen patients were divided into three groups: control non-COPD (n=7), smoker non-COPD (n=7), and COPD (n=5). The emphysema mouse model defined as the CS exposure group was induced by CS exposure plus cigarette smoke extract (CSE) intraperitoneal injection for 28 days. Primary PMVECs were isolated from the mouse by magnetic bead sorting method via CD31-Dynabeads. Apoptosis was detected by western blot and flow cytometry. RESULTS: LRG1 was increased in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. KLK10 was over-expressed in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. LRG1 promoted apoptosis in PMVECs. LRG1 knockdown reversed CSE-induced apoptosis in PMVECs. The mRNA and protein expression of KLK10 were increased after over-expressed LRG1 in PMVECs isolated from mice. Similarly, both the mRNA and protein levels of KLK10 were decreased after LRG1 knockdown in PMVECs. The result of co-immunoprecipitation revealed a protein-protein interaction between LRG1 and KLK10 in PMVECs. KLK10 promoted apoptosis via the down-regulation of Bcl-2/Bax in PMVECs. KLK10 knockdown could reverse CSE-induced apoptosis in PMVECs. CONCLUSIONS: LRG1 promotes apoptosis via up-regulation of KLK10 in PMVECs isolated from mice. KLK10 promotes apoptosis via the down-regulation of Bcl-2/Bax in PMVECs. There was a direct protein-protein interaction between LRG1 and KLK10 in PMVECs. Our novel findings provide insights into the understanding of LRG1/KLK10 function as a potential molecule in COPD.

Multi-Instance Learning for Vocal Fold Leukoplakia Diagnosis Using White Light and Narrow-Band Imaging: A Multicenter Study.

OBJECTIVES: Vocal fold leukoplakia (VFL) is a precancerous lesion of laryngeal cancer, and its endoscopic diagnosis poses challenges. We aim to develop an artificial intelligence (AI) model using white light imaging (WLI) and narrow-band imaging (NBI) to distinguish benign from malignant VFL. METHODS: A total of 7057 images from 426 patients were used for model development and internal validation. Additionally, 1617 images from two other hospitals were used for model external validation. Modeling learning based on WLI and NBI modalities was conducted using deep learning combined with a multi-instance learning approach (MIL). Furthermore, 50 prospectively collected videos were used to evaluate real-time model performance. A human-machine comparison involving 100 patients and 12 laryngologists assessed the real-world effectiveness of the model. RESULTS: The model achieved the highest area under the receiver operating characteristic curve (AUC) values of 0.868 and 0.884 in the internal and external validation sets, respectively. AUC in the video validation set was 0.825 (95% CI: 0.704-0.946). In the human-machine comparison, AI significantly improved AUC and accuracy for all laryngologists (p < 0.05). With the assistance of AI, the diagnostic abilities and consistency of all laryngologists improved. CONCLUSIONS: Our multicenter study developed an effective AI model using MIL and fusion of WLI and NBI images for VFL diagnosis, particularly aiding junior laryngologists. However, further optimization and validation are necessary to fully assess its potential impact in clinical settings. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Gypenoside XVII Reduces Synaptic Glutamate Release and Protects against Excitotoxic Injury in Rats.

Excitotoxicity is a common pathological process in neurological diseases caused by excess glutamate. The purpose of this study was to evaluate the effect of gypenoside XVII (GP-17), a gypenoside monomer, on the glutamatergic system. In vitro, in rat cortical nerve terminals (synaptosomes), GP-17 dose-dependently decreased glutamate release with an IC50 value of 16 µM. The removal of extracellular Ca2+ or blockade of N-and P/Q-type Ca2+ channels and protein kinase A (PKA) abolished the inhibitory effect of GP-17 on glutamate release from cortical synaptosomes. GP-17 also significantly reduced the phosphorylation of PKA, SNAP-25, and synapsin I in cortical synaptosomes. In an in vivo rat model of glutamate excitotoxicity induced by kainic acid (KA), GP-17 pretreatment significantly prevented seizures and rescued neuronal cell injury and glutamate elevation in the cortex. GP-17 pretreatment decreased the expression levels of sodium-coupled neutral amino acid transporter 1, glutamate synthesis enzyme glutaminase and vesicular glutamate transporter 1 but increased the expression level of glutamate metabolism enzyme glutamate dehydrogenase in the cortex of KA-treated rats. In addition, the KA-induced alterations in the N-methyl-D-aspartate receptor subunits GluN2A and GluN2B in the cortex were prevented by GP-17 pretreatment. GP-17 also prevented the KA-induced decrease in cerebral blood flow and arginase II expression. These results suggest that (i) GP-17, through the suppression of N- and P/Q-type Ca2+ channels and consequent PKA-mediated SNAP-25 and synapsin I phosphorylation, reduces glutamate exocytosis from cortical synaptosomes; and (ii) GP-17 has a neuroprotective effect on KA-induced glutamate excitotoxicity in rats through regulating synaptic glutamate release and cerebral blood flow.

Multiple RNA Rapid In Situ Imaging Based on Cas9 Code Key System.

Existing RNA in situ imaging strategies mostly utilize parallel repetitive nucleic acid self-assembly to achieve multiple analysis, with limitations of complicated systems and cumbersome steps. Here, a Cas9 code key system with key probe (KP) encoder and CRISPR/Cas9 signal exporter is developed. This system triggers T-protospacer adjacent motif (T-PAM structural transitions of multiple KP encoders to form coding products with uniform single-guide RNA (sgRNA) target sequences as tandem nodes. Only single sgRNA/Cas9 complex is required to cleave multiple coding products, enabling efficient "many-to-one" tandem signaling, and non-collateral cleavage activity-dependent automatic signaling output through active introduction of mismatched bases. Compared with conventional parallel multiple signaling analysis model, the proposed system greatly simplifies reaction process and enhances detection efficiency. Further, a rapid multiple RNA in situ imaging system is developed by combining the Cas9 code key system with a T-strand displacement amplification (T-SDA) signal amplifier. The constructed system is applied to tumor cells and clinicopathology slices, generating clear multi-mRNA imaging profiles in less than an hour with just one step. Therefore, this work provides reliable technical support for clinical tumor typing and molecular mechanism investigation.

Persistence of SARS-CoV-2 colonization and high expression of inflammatory factors in cardiac tissue 6 months after COVID-19 recovery: a prospective cohort study.

Background: The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in myocardial autopsy tissues has been observed in certain individuals with coronavirus disease 2019 (COVID-19). However, the duration of cardiac involvement remains uncertain among recovered COVID-19 patients. Our study aims to evaluate the long-term persistence of SARS-CoV-2 within cardiac tissue. Methods: We prospectively and consecutively evaluated the patients undergoing mitral valve replacement (MVR) and left atrial (LA) volume reduction surgery from May 25 to June 10, 2023 at our center, who had been approximately 6 months of recovery after Omicron wave. Patients tested positive for SARS-CoV-2 upon admission were excluded. The surgical LA tissue was collected in RNA preservation solution and stored at -80 ℃ immediately. Then SARS-CoV-2, interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) RNA expression in LA tissues were assessed through thrice-repeated reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Categorical variables were assessed using the Chi-square or Fisher's exact tests, and continuous variables was analyzed using the Mann-Whitney U test. Results: Nine of 41 patients were enrolled, all of whom tested negative for SARS-CoV-2 upon admission (two antigen and PCR tests). In four of nine patients, SARS-CoV-2 RNA was detected in their LA tissue, indicating viral colonization. Among the four positive cases, the IL-6 and IL-1ß relative expression levels in the LA tissue of one patient were increased approximately 55- and 110-fold, respectively, compared to those of SARS-CoV-2 (-) patients. Increased expression of IL-6 and IL-1ß were observed in the myocardium of this patient. Another patient demonstrated a remarkable 7-fold increase in both IL-6 and IL-1ß expression, surpassing that of SARS-CoV-2 (-) patients. Additionally, no other cardiac inflammation-related diseases or conditions were presented in these two patients. The IL-6 and IL-1ß expression levels of the remaining two patients were not significantly different from those of SARS-CoV-2 (-) patients. The relative expression levels of IL-6 and IL-1ß in cardiac tissues of all SARS-CoV-2 (-) patients were relatively low. Interestingly, despite abnormally elevated levels of IL-6 and IL-1ß within their cardiac tissue, two patients did not show a significant increase in serum IL-6 and IL-1ß levels when compared to other patients. Conclusions: Our research suggests that certain COVID-19-recovered patients have persistent colonization of SARS-CoV-2 in their cardiac tissue, accompanied by a local increase in inflammatory factors.

The concomitant use of the renin-angiotensin system inhibitors and survival outcomes of patients with pancreatic adenocarcinoma: an analysis from a tertiary center.

Background: The limited efficacy of chemotherapy in improving survival in pancreatic ductal adenocarcinoma (PDAC) necessitates the exploration of novel strategies to overcome treatment resistance. Objectives: This study aimed to investigate the impact of combining renin-angiotensin system (RAS) blockers with chemotherapy on survival outcomes in patients with PDAC. Design: Patients with PDAC were enrolled in the retrospective study. Methods: We analyzed patients with PDAC (n = 384) at our institution between 2014 and 2021. Survival outcomes, including event-free survival (EFS) and overall survival (OS), were analyzed according to the concomitant use of RAS blockers. Results: Among the 384 patients in the study, 70 (18.2%) concomitantly received angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Patients in the ACEI/ARB group, characterized by older age and more comorbidities, displayed a significantly superior 12-month EFS rate (22.86% versus 13.69%, p = 0.008) compared to the non-ACEI/ARB group, while OS remained similar between the groups. In the multivariate analysis, the use of ACEI/ARB was associated with better 12-month EFS (hazards ratio = 0.71, 95% confidence interval: 0.52-0.96; p = 0.024). Poor performance, advanced disease status, and higher CA19-9 levels were associated with poor survival outcomes. Conclusion: Concomitant use of ACEIs/ARBs in patients with pancreatic cancer resulted in significantly better 12-month EFS. Age, performance status, disease status, and higher CA19-9 levels were independent predictors of survival. The combination strategy might provide better treatment outcomes in patients with PDAC.

Cold hypersensitivity in the hands and feet is associated with erectile dysfunction in young Taiwanese men.

Cold hypersensitivity in the hands and feet (CHHF) is a protective or predisposing factor for many diseases; however, the relationship between CHHF and erectile dysfunction (ED) remains unclear. We aimed to investigate associations between CHHF and ED among young men of Southeast Asian origin. In this cross-sectional study, sexually active Taiwanese men aged 20-40 years were enrolled via an online questionnaire comprising general demographic information, comorbidities, subjective thermal sensations of their hands and feet in the past 6 months, and their erectile function using the International Index of Erectile Function-5 (IIEF-5). Participants who reported cold sensation of hands and feet were classified to have CHHF; those with IIEF-5 score ≤ 21 were considered to have ED. Total 54.2% and 27.9% of participants had ED and CHHF, respectively. Men with CHHF were significantly younger, had lower body mass index and IIEF-5 scores (p < 0.001), and a lower prevalence of diabetes mellitus (p = 0.033) along with higher prevalence of ED, psychiatric disorders, and insomnia (p < 0.001). After adjusting for predisposing factors of ED, CHHF (odds ratio 1.410, 95% confidence interval 1.159-1.714; p = 0.001) remained an independent predictor of ED. Thus, CHHF is independently associated with ED, affecting more than a quarter of young Taiwanese men. Autonomic dysregulation and subclinical endothelial dysfunction may be common pathophysiologies of CHHF and ED.

ADAM9 drives the immunosuppressive microenvironment by cholesterol biosynthesis-mediated activation of IL6-STAT3 signaling for lung tumor progression.

Chronic inflammation associated with lung cancers contributes to immunosuppressive tumor microenvironments, reducing CD8+ T-cell function and leading to poor patient outcomes. A disintegrin and metalloprotease domain 9 (ADAM9) promotes cancer progression. Here, we aim to elucidate the role of ADAM9 in the immunosuppressive tumor microenvironment. A bioinformatic analysis of TIMER2.0 was used to investigate the correlation of ADAM9 and to infiltrate immune cells in the human lung cancer database and mouse lung tumor samples. Flow cytometry, immunohistochemistry, and RNA sequencing (RNA-seq) were performed to investigate the ADAM9-mediated immunosuppressive microenvironment. The coculture system of lung cancer cells with immune cells, cytokine array assays, and proteomic approach was used to investigate the mechanism. By analyzing the human LUAD database and the mouse lung cancer models, we showed that ADAM9 was associated with the immunosuppressive microenvironment. Additionally, ADAM9 released IL6 protein from cancer cells to inhibit IL12p40 secretion from dendritic cells, therefore leading to dendritic cell dysfunction and further affecting T-cell functions. Proteomic analysis indicated that ADAM9 promoted cholesterol biosynthesis and increased IL6-STAT3 signaling. Mechanistically, ADAM9 reduced the protein stability of LDLR, resulting in reduced cholesterol uptake and induced cholesterol biosynthesis. Moreover, LDLR reduction enhanced IL6-STAT3 activation. We reveal that ADAM9 has a novel biological function that drives the immunosuppressive tumor microenvironment by linking lung cancer's metabolic and signaling axes. Thus, by targeting ADAM9 an innovative and promising therapeutic opportunity was indicated for regulating the immunosuppression of lung cancer.

Unilateral biportal endoscopy via two different approaches for upper lumbar disc herniation: a technical note.

BACKGROUND: The traditional surgical procedures for upper lumbar disc herniation (ULDH) usually lead to frequent complications. We aim to investigate the clinical efficacy of the unilateral biportal endoscopy (UBE) technique in treating upper lumbar disc herniation (ULDH). METHODS: From January 2020 to December 2021, the clinical data of 28 patients with ULDH treated with the UBE technique were collected and analyzed for surgery time under UBE, postsurgical drainage, postsurgical hospital stay, and complications. The clinical efficacy was evaluated according to the modified MacNab score, Oswestry disability index (ODI), and visual analogue scale (VAS) of low back pain and lower limb pain before the surgery; one week, one month, and three months after the surgery; and at the last follow-up. RESULTS: All patients underwent the UBE surgery successfully. The surgery time under UBE for non-fusion cases was 47.50 ± 11.84 min (monosegment) and 75.00 ± 20.66 min (two segments), while that for fusion cases was 77.50 ± 21.02 min. The postsurgical drainage for non-fusion cases was 25.00 ± 13.94 mL (monosegment) and 38.00 ± 11.83 mL (two segments), while that for fusion cases was 71.25 ± 31.72 mL. The postsurgical hospital stay was 8.28 ± 4.22 days. The follow-up time was 15.82 ± 4.54 months. The VAS score for each time period after the surgery was significantly lower (P < 0.05), while the ODI was significantly higher than that before the surgery (P < 0.05). According to the modified MacNab scoring standard, the ratio of excellent to good was 96.43% at the last follow-up. Two patients experienced transient numbness and pain in their lower limbs and no activity disorder after the surgery, and they recovered after conservative treatment. CONCLUSIONS: The clinical effect of UBE technique in treating ULDH was reliable. According to the needs of the disease, the interlaminar approach or paraspinal approach of the UBE technique was selected. This technique took into account the effect of treatment, achieved the purpose of minimal invasiveness, and did not require special instruments. Therefore, it has the potential for clinical application.

Discharge within 24 h, transvaginal natural orifice transluminal endoscopic surgery- more suitable for ambulatory surgery in gynecology procedures: a retrospective study.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is an achievement in the field of minimally invasive surgery. However, the vantage point of vaginal natural orifice transluminal endoscopic surgery (vNOTES) in gynecologicalprocedures remains unclear. The main purpose of this study was to compare vNOTES with laparo-endoscopic single-site surgery, and to determine which procedure is more suitable for ambulatory surgery in gynecologic procedures. METHODS: This retrospective observational study was conducted at the Department of Gynecology, Chengdu Women's and Children's Central Hospital. The 207 enrolled patients had accepted vNOTES and laparo-endoscopic single-site surgery in gynecology procedures from February 2021 to March 2022. Surgically relevant information regarding patients who underwent ambulatory surgery was collected, and 64 females underwent vNOTES. RESULTS: Multiple outcomes were analyzed in 207 patients. The Wilcoxon Rank-Sum test showed that there were statistically significant differences between the vNOTES and laparo-endoscopic single-site surgery groups in terms of postoperative pain score (0 vs. 1 scores, p = 0.026), duration of anesthesia (90 vs. 101 min, p = 0.025), surgery time (65 vs. 80 min, p = 0.015), estimated blood loss (20 vs. 40 mL, p < 0.001), and intestinal exhaustion time (12.20 vs. 17.14 h, p < 0.001). Treatment with vNOTES resulted in convenience, both with respect to time savings and hemorrhage volume in surgery and with respect to the quality of the prognosis. CONCLUSION: These comprehensive data reveal the capacity of vNOTES to increase surgical efficiency. vNOTES in gynecological procedures may demonstrate sufficient feasibility and provide a new medical strategy compared with laparo-endoscopic single-site surgery for ambulatory surgery in gynecological procedures.