A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management.

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

Visual reading for [18F]Florzolotau Tau PET scans in progressive supranuclear palsy.

PURPOSE: The identification of tau accumulation within living brains holds significant potential in facilitating accurate diagnosis of progressive supranuclear palsy (PSP). While visual assessment is frequently employed, standardized methods for tau positron emission tomography (PET) specifically in PSP are absent. We aimed to develop a visual reading algorithm dedicated to the evaluation of [18F]Florzolotau PET in PSP. METHODS: 148 PSP and 30 healthy volunteers were divided into a development set (for the establishment of the reading rules; n = 89) and a testing set (for the validation of the reading rules; n = 89). For differential diagnosis, 55 α-synucleinopathies were additionally included into the testing set. The visual reading method was established by an experienced assessor (Reader 0) and was then validated by Reader 0 and two additional readers on regional and overall binary manners. A positive binding in both midbrain and globus pallidus/putamen regions was characterized as a PSP-like pattern, whereas any other pattern was classified as non-PSP-like. RESULTS: Reader 1 (94.4%) and Reader 2 (93.8%) showed excellent agreement for the overall binary determination against Reader 0. The regional binary determinations of midbrain and globus pallidus/putamen showed excellent agreement among readers (kappa > 0.80). The overall binary evaluation demonstrated reproducibility of 86.1%, 94.4% and 77.8% for three readers. The visual reading algorithm showed high agreement with regional standardized uptake value ratios and clinical diagnoses. CONCLUSION: Through the application of the suggested visual reading algorithm, [18F]Florzorotau PET imaging demonstrated a robust performance for the imaging diagnosis of PSP.

Microrna363-5p targets thrombospondin3 to regulate pathological cardiac remodeling.

Cardiac remodeling is an end-stage manifestation of multiple cardiovascular diseases, and microRNAs are involved in a variety of posttranscriptional regulatory processes. miR-363-5p targeting Thrombospondin3 (THBS3) has been shown to play an important regulatory role in vascular endothelial cells, but the roles of these two in cardiac remodeling are unknown. Firstly, we established an in vivo model of cardiac remodeling by transverse aortic narrow (TAC), and then we stimulated a human cardiomyocyte cell line (AC16) and a human cardiac fibroblast cell line (HCF) using 1 µmol/L angiotensin II (Ang II) to establish an in vitro model of cardiac hypertrophy and an in vitro model of myocardial fibrosis, respectively. In all three of the above models, we found a significant decreasing trend of miR-363-5p, suggesting that it plays a key regulatory role in the occurrence and development of cardiac remodeling. Subsequently, overexpression of miR-363-5p significantly attenuated myocardial hypertrophy and myocardial fibrosis in vitro as evidenced by reduced the area of AC16, the cell viability of HCFs, the relative expression of the protein of fetal genes (ANP, BNP, ß-MHC) and fibrosis marker (collagen I, collagen III, α-SMA), whereas inhibition of miR-363-5p expression showed the opposite trend. In addition, we also confirmed the targeted binding relationship between miR-363-5p and THBS3 by dual luciferase reporter gene assay, and the expression of THBS3 was directly inhibited by miR-363-5p. Moreover, overexpression of miR-363-5p with THBS3 simultaneously partially eliminated the delaying effect of miR-363-5p on myocardial hypertrophy and myocardial fibrosis in vitro. In conclusion, Overexpression of miR-363-5p attenuated the prohypertrophic and profibrotic effects of Ang II on AC16 and HCF by a mechanism related to the inhibition of THBS3 expression.

Comprehensive Proteomic Analysis of Dysferlinopathy Unveiling Molecular Mechanisms and Biomarkers Linked to Pathological Progression.

AIMS: Previous proteomics studies in dysferlinopathy muscle have been limited in scope, often utilizing 2D-electrophoresis and yielding only a small number of differential expression calls. To address this gap, this study aimed to employ high-resolution proteomics to explore the proteomic landscapes of dysferlinopathy and analyze the correlation between muscle pathological changes and alterations in protein expression in muscle biopsies. METHODS: We conducted a comprehensive approach to investigate the proteomic profile and disease-associated changes in the muscle tissue proteome from 15 patients with dysferlinopathy, exhibiting varying degrees of dystrophic pathology, alongside age-matched controls. Our methodology encompasses tandem mass tag (TMT)-labeled liquid chromatography-mass spectrometry (LC-MS/MS)-based proteomics, protein-protein interaction (PPI) network analysis, weighted gene co-expression network analysis, and differential expression analysis. Subsequently, we examined the correlation between the expression of key proteins and the clinical characteristics of the patients to identify pathogenic targets associated with DYSF mutations in dysferlinopathy. RESULTS: A total of 1600 differentially expressed proteins were identified, with 1321 showing high expression levels and 279 expressed at lower levels. Our investigation yields a molecular profile delineating the altered protein networks in dysferlinopathy-afflicted skeletal muscle, uncovering dysregulation across numerous cellular pathways and molecular processes, including mRNA metabolic processes, regulated exocytosis, immune response, muscle system processes, energy metabolic processes, and calcium transmembrane transport. Moreover, we observe significant associations between the protein expression of ANXA1, ANXA2, ANXA4, ANXA5, LMNA, PYGM, and the extent of histopathologic changes in muscle biopsies from patients with dysferlinopathy, validated through immunoblotting and immunofluorescence assays. CONCLUSIONS: Through the aggregation of expression data from dysferlinopathy-impacted muscles exhibiting a range of pathological alterations, we identified multiple key proteins associated with the dystrophic pathology of patients with dysferlinopathy. These findings provide novel insights into the pathogenesis of dysferlinopathy and propose promising targets for future therapeutic endeavors.

Bowel preparation experiences and needs before follow-up colonoscopy in older adult postoperative colorectal cancer patients: A qualitative study.

BACKGROUND: The bowel preparation process prior to colonoscopy determines the quality of the bowel preparation, which in turn affects the quality of the colonoscopy. Colonoscopy is an essential procedure for postoperative follow-up monitoring of colorectal cancer (CRC) patients. Previous studies have shown that advanced age and a history of colorectal resection are both risk factors for inadequate bowel preparation. However, little attention has been paid to the bowel preparation experiences and needs of predominantly older adult postoperative CRC patients. AIM: To explore the experiences and needs of older adult postoperative CRC patients during bowel preparation for follow-up colonoscopy. METHODS: Fifteen older adult postoperative CRC patients who underwent follow-up colonoscopy at a tertiary hospital in Shanghai were selected using purposive sampling from August 2023 to November 2023. The phenomenological method in qualitative research was employed to construct an interview outline and conduct semi-structured interviews with the patients. Colaizzi's seven-step analysis was utilized to organize, code, categorize, summarize, and verify the interview data. RESULTS: The results of this study were summarized into four themes and eight sub-themes: (1) Inadequate knowledge about bowel preparation; (2) Decreased physiological comfort during bowel preparation (gastrointestinal discomfort and sleep deprivation caused by bowel cleansing agents, and hunger caused by dietary restrictions; (3) Psychological changes during different stages of bowel preparation (pre-preparation: Fear and resistance due to previous experiences; during preparation: Irritation and helplessness caused by taking bowel cleansing agents, and post-preparation: Anxiety and worry while waiting for the colonoscopy); and (4) Needs related to bowel preparation (detailed instructions from healthcare professionals; more ideal bowel cleansing agents; and shortened waiting times for colonoscopy). CONCLUSION: Older adult postoperative CRC patients' knowledge of bowel preparation is not adequate, and they may encounter numerous difficulties and challenges during the process. Healthcare professionals should place great emphasis on providing instruction for their bowel preparation.

Significance of detecting cardiac troponin I and creatine kinase MB in critically Ill children without primary cardiac illness.

Objective: To investigate the incidence of myocardial injury in children with critically ill children without primary cardiac disease and the association between elevated cardiac troponin I (cTnl) and creatine kinase MB (CK-MB) concentrations and disease progression and prognosis to guide early treatment. Methods: The serum cTnI and CK-MB concentrations of 292 children with critically ill children without primary cardiac disease in Yantai Yuhuangding Hospital between January 2021 and January 2024 were retrospectively analyzed within 24 h after entering the Pediatric Intensive Care Unit (PICU). The children were divided into normal and abnormal groups according to the myocardial marker results. The abnormal group was further divided into the cTnI-elevated, CK-MB-elevated, single-elevated (cTnI- or CK-MB-elevated) and double-elevated (cTnI- and CK-MB-elevated) groups. The differences in the clinical indicators and their relationships with prognosis for the groups were compared. Results: The incidence of myocardial injury among the critically ill children without primary cardiac disease was 55.1%. The incidence of myocardial injury in children with infectious diarrhea combined with moderate and severe dehydration reached 85.19%. The pediatric critical illness score; frequency of use of vasoactive drugs; hypotension, shock, heart failure, respiratory failure, and multiple organ dysfunction syndrome; and mortality indexes differed significantly for the normal and abnormal myocardial marker groups (P < 0.05). The single-elevated and normal groups only showed a difference in mortality (P < 0.017). The cTnI and CK-MB concentrations were negatively correlated with prognosis (P < 0.01). Conclusion: Myocardial injury, as evidenced by elevated cardiac biomarkers, is common in critically ill children without primary cardiac illness. cTnI and CK-MB are associated with outcomes. Shock, heart failure, and multiple organ dysfunction syndromes are independently associated with simultaneous elevations of CK-MB and cTnI concentrations. Further prospective studies are needed to elucidate the clinical utility of these biomarkers.

Waterborne polyurethane nanoparticles incorporating linoleic acid as a potential strategy for controlling antibiotic resistance spread in the mammalian intestine.

Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro, but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU0.89@LA, WPU0.99@LA, WPU1.09@LA, and WPU1.19@LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU0.99@LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU0.99@LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU0.99@LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU0.99@LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.

Effect of Different Insertion Methods on LMA Protector-Related Complications: A Prospective Randomized Double-Blind Clinical Trail.

OBJECTIVE: The authors compared the effect of 2 insertion methods, namely the conventional laryngeal mask airway (LMA) insertion and the index finger-assisted LMA insertion, on the incidence of complications associated with LMA Protector insertion. METHODS: The authors enrolled 300 patients, who underwent painless bronchoscopy. The patients ranged in age between 18 and 75 and were classified as American Society of Anesthesiologists grade I to III. They were randomly divided into 2 groups: a control group of 150 patients and an assisted group comprising 150 patients. LMA was inserted using the conventional and index finger-assisted insertion methods in both groups, respectively. The primary outcome was postoperative complications, such as oral mucosal injury and pharyngeal pain. Secondary outcomes included the success rate of first-time insertion, the incidence rate of inverse folding of LMA tips, oropharyngeal leak pressure (OLP), and other postoperative complications. RESULTS: Compared with the conventional LMA insertion method, index finger-assisted LMA insertion can significantly reduce the incidence rate of oral mucosal injury and pharyngeal pain, with fewer insertion failures. There was a statistically significant difference between the 2 groups in the visual field grading before adjustment for LMA alignment (P<0.0001). The conventional insertion method increased the likelihood of inverse folding of LMA tips. When the conventional insertion method was utilized, there was a significant difference in airway pressure and tidal volume before and after alignment under a fiberoptic bronchoscope (P<0.0001), but no significant difference in visual field grading and respiratory mechanics-related indicators. CONCLUSIONS: Index finger-assisted insertion can significantly reduce the incidence rate of LMA Protector-related complications and inverse folding of LMA tips.

Beyond weight loss: the potential of glucagon-like peptide-1 receptor agonists for treating heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various phenotypes, and obesity is one of the most common and clinically relevant phenotypes of HFpEF. Obesity contributes to HFpEF through multiple mechanisms, including sodium retention, neurohormonal dysregulation, altered energy substrate metabolism, expansion of visceral adipose tissue, and low-grade systemic inflammation. Glucagon-like peptide-1 (GLP-1) is a hormone in the incretin family. It is produced by specialized cells called neuroendocrine L cells located in the distal ileum and colon. GLP-1 reduces blood glucose levels by promoting glucose-dependent insulin secretion from pancreatic ß cells, suppressing glucagon release from pancreatic α cells, and blocking hepatic gluconeogenesis. Recent evidence suggests that GLP-1 receptor agonists (GLP-1 RAs) can significantly improve physical activity limitations and exercise capacity in obese patients with HFpEF. The possible cardioprotective mechanisms of GLP-1 RAs include reducing epicardial fat tissue thickness, preventing activation of the renin-angiotensin-aldosterone system, improving myocardial energy metabolism, reducing systemic inflammation and cardiac oxidative stress, and delaying the progression of atherosclerosis. This review examines the impact of obesity on the underlying mechanisms of HFpEF, summarizes the trial data on cardiovascular outcomes of GLP-1 RAs in patients with type 2 diabetes mellitus, and highlights the potential cardioprotective mechanisms of GLP-1 RAs to give a pathophysiological and clinical rationale for using GLP-1 RAs in obese HFpEF patients.

mTOR signalling controls the formation of smooth muscle cell-derived luminal myofibroblasts during vasculitis.

The accumulation of myofibroblasts within the intimal layer of inflamed blood vessels is a potentially catastrophic complication of vasculitis, which can lead to arterial stenosis and ischaemia. In this study, we have investigated how these luminal myofibroblasts develop during Kawasaki disease (KD), a paediatric vasculitis typically involving the coronary arteries. By performing lineage tracing studies in a murine model of KD, we reveal that luminal myofibroblasts develop independently of adventitial fibroblasts and endothelial cells, and instead derive from smooth muscle cells (SMCs). Notably, the emergence of SMC-derived luminal myofibroblasts-in both mice and patients with KD, Takayasu's arteritis and Giant Cell arteritis-coincided with activation of the mechanistic target of rapamycin (mTOR) signalling pathway. Moreover, SMC-specific deletion of mTOR signalling, or pharmacological inhibition, abrogated the emergence of luminal myofibroblasts. Thus, mTOR is an intrinsic and essential regulator of luminal myofibroblast formation that is activated in vasculitis patients and therapeutically tractable. These findings provide molecular insight into the pathogenesis of coronary artery stenosis and identify mTOR as a therapeutic target in vasculitis.

A Multi-Scale Liver Tumor Segmentation Method Based on Residual and Hybrid Attention Enhanced Network with Contextual Integration.

Liver cancer is one of the malignancies with high mortality rates worldwide, and its timely detection and accurate diagnosis are crucial for improving patient prognosis. To address the limitations of traditional image segmentation techniques and the U-Net network in capturing fine image features, this study proposes an improved model based on the U-Net architecture, named RHEU-Net. By replacing traditional convolution modules in the encoder and decoder with improved residual modules, the network's feature extraction capabilities and gradient stability are enhanced. A Hybrid Gated Attention (HGA) module is integrated before the skip connections, enabling the parallel processing of channel and spatial attentions, optimizing the feature fusion strategy, and effectively replenishing image details. A Multi-Scale Feature Enhancement (MSFE) layer is introduced at the bottleneck, utilizing multi-scale feature extraction technology to further enhance the expression of receptive fields and contextual information, improving the overall feature representation effect. Testing on the LiTS2017 dataset demonstrated that RHEU-Net achieved Dice scores of 95.72% for liver segmentation and 70.19% for tumor segmentation. These results validate the effectiveness of RHEU-Net and underscore its potential for clinical application.

2-Arylbenzofurans from the stems and leaves of Artocarpus tonkinensis and their potential antiproliferative activities.

Phytochemical study on the stems and leaves of Artocarpus tonkinensis led to the isolation of a new 2-arylbenzofuran, artocartone (1), as well as seven known 2-arylbenzofurans (2-8). The chemical structure of 1 was established by means of comprehensive spectroscopic analyses and the known compounds were determined by comparing their MS and NMR data with those reported data in literature. The antiproliferative activities of all isolates 1-8 against five human cancer cell lines: HL-60, SMMC-7721, A-375, MCF-7 and SW480 in vitro were evaluated. As a result, compounds 1- 8 displayed notable antiproliferative activities against various human cancer cell lines with IC50 values in the range of 0.28 ± 0.05-26.89 ± 0.18 µM.

Enhancement of Apple Stress Resistance via Proline Elevation by Sugar Substitutes.

Plants encounter numerous adversities during growth, necessitating the identification of common stress activators to bolster their resistance. However, the current understanding of these activators' mechanisms remains limited. This study identified three anti-stress activators applicable to apple trees, all of which elevate plant proline content to enhance resistance against various adversities. The results showed that the application of these sugar substitutes increased apple proline content by two to three times compared to the untreated group. Even at a lower concentration, these activators triggered plant stress resistance without compromising apple fruit quality. Therefore, these three sugar substitutes can be exogenously sprayed on apple trees to augment proline content and fortify stress resistance. Given their effectiveness and low production cost, these activators possess significant application value. Since they have been widely used in the food industry, they hold potential for broader application in plants, fostering apple industry development.

Adsorption Performance of Modified Graphite from Synthetic Dyes Solutions.

Due to the severe harmful impacts of industrial dyeing wastewater on ecosystems and human health, proper treatment is crucial. Herein, the use of modified graphite as an adsorbent for dyeing wastewater treatment was investigated in this study. The graphite was oxidized and intercalated using a phosphoric acid-nitric acid-potassium permanganate system and then thermally treated at high temperatures to optimize its structure. By adjusting the thermal treatment temperature, the graphite adsorbent with varying porosity was obtained. The optimized graphite demonstrated significant improvement in adsorption performance for dyes and organic compounds, achieving a removal rate of over 85% for methylene blue (MB) dye. The optimal adsorption performance is achieved with a 1.6 mg modified graphite adsorbent at 60 °C under alkaline conditions for adsorbing 10 ppm MB. Adsorption kinetics and isotherm models were applied to elucidate the adsorption mechanisms. The results fit the Langmuir model, suggesting that monolayer homogeneous adsorption is favorable. Importantly, the results demonstrate that high-temperature treatment can significantly enhance the adsorption properties of coal-based graphite, supporting its application in dyeing wastewater treatment.

Zeta class glutathione S-transferase is involved in phoxim tolerance and is potentially regulated by the transcription factor CncC in Agrotis ipsilon (Lepidoptera: Noctuidae).

The black cutworm, Agrotis ipsilon (Lepidoptera: Noctuidae), is an important agricultural pest. Phoxim is an organophosphate insecticide that has been widely used to control A. ipsilon. The extensive application of phoxim has resulted in a reduction in phoxim susceptibility in A. ipsilon. However, the molecular mechanisms underlying phoxim tolerance in A. ipsilon remain unclear. In this work, we report the involvement of AiGSTz1, a zeta class glutathione S-transferase, in phoxim tolerance in A. ipsilon. Exposure to a sublethal concentration (LC50) of phoxim dramatically upregulated the transcription level of the AiGSTz1 gene in A. ipsilon larvae, and this upregulation might be caused by phoxim-induced oxidative stress. The recombinant AiGSTz1 protein expressed in Escherichia coli was able to metabolize phoxim. Furthermore, AiGSTz1 displayed antioxidant activity to protect against oxidative stress. Knockdown of AiGSTz1 by RNA interference significantly increased the mortality rate of A. ipsilon larvae in response to phoxim. In addition, the transcription factor AiCncC can bind to the cap 'n' collar isoform C: muscle aponeurosis fibromatosis (CncC:Maf) binding site in the putative promoter of the AiGSTz1 gene. Silencing of AiCncC resulted in a dramatic downregulation of AiGSTz1. These results indicated that AiGSTz1 is involved in phoxim tolerance and is potentially regulated by AiCncC. These findings provide valuable insights into the defense mechanisms used by A. ipsilon against phoxim.

Monitoring Lung Function with Electrical Impedance Tomography in the Intensive Care Unit.

Electrical Impedance Tomography (EIT) is a groundbreaking, non-invasive, and radiation-free imaging technique for continuous, real-time ventilation monitoring. It also has an application in pulmonary perfusion monitoring. EIT quantifies ventilation and perfusion patterns across the lung from the measurement and processing of impedance changes in the thorax. It is a powerful tool for clinicians to visualize breath-by-breath changes in pulmonary function. An innovative application of EIT is its ability to assess pulmonary perfusion using the kinetic analysis of a hypertonic solution injection during a breath-hold. The solution generates an impedance change in the thorax as it circulates through the pulmonary vasculature. This indirect method allows for the estimation of perfusion patterns, contributing significantly to our understanding of pulmonary blood flow dynamics at the bedside. EIT is not just a tool for monitoring but also can be critical for the diagnosis of respiratory pathologies such as pneumothorax and bronchial intubation. It can help identify the etiology of ventilation/perfusion (V/Q) mismatch in patients receiving invasive mechanical ventilation, which is not possible with other diagnostic tools. Moreover, EIT can assist in the individual optimization of ventilator settings, such as Positive End-Expiratory Pressure (PEEP) titration and tidal volume improving oxygenation and lung health in critical care. In summary, EIT represents a paradigm shift in bedside pulmonary monitoring and diagnostics. Its non-invasive nature and immediacy of data make EIT an indispensable tool in modern respiratory medicine. With its growing applications, EIT will be pivotal in advancing our understanding of and approach to respiratory care, particularly in intensive care settings.

Spinal PTP1B Regulated NMDA Receptor-mediated Nociceptive Transmission and Peripheral Inflammation-induced Pain Sensitization.

Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of several pain-related substrates in spinal cord dorsal horn and are critically involved in the modification of pain transmission. The current study demonstrated that protein tyrosine phosphatase 1B (PTP1B), a unique endoplasmic reticulum-resident member of PTP family, displayed an activity-dependent increase in its protein expression and synaptic localization in spinal dorsal horn of adult male rats. PTP1B interacted with the Src Homology 3 (SH3) domain of Synapse-Associated Protein 102 (SAP102), one of the postsynaptic scaffolding proteins that anchored PTP1B at postsynaptic sites. The SAP102-tethered PTP1B augmented the synaptic transmission mediated specifically by GluN2B subunit-containing N-methyl-D-aspartate subtype glutamate receptors. Interference with PTP1B activity or disruption of its interaction with SAP102 attenuated GluN2B-mediated nociceptive transmission and ameliorated pain sensitization induced by intraplantar injection of Complete Freund's Adjuvant. These data suggested that the activity-dependent synaptic redistribution of PTP1B served as an important mechanism regulating GluN2B receptor activity and that manipulation of PTP1B synaptic targeting might represent an effective approach for the treatment of chronic inflammatory pain.

Improving Sexual Function through Penis Enlargement: Comparing Silicone Pearls Implantation and Fat Grafting.

BACKGROUND: Although current penile enlargement techniques can improve appearance, it remains unclear whether these procedures increase sexual function. We aimed to systematically compare the surgical outcomes, with a particular focus on sexual function, in patients and their partners following silicone pearls implantation and fat grafting for penis enlargement. METHODS: A single-site, retrospective study reviewed patients who underwent silicone pearls implantation or fat grafting for penis enlargement. In the operation, silicone pears were connected to form a ring-shaped implant, which was then implanted under the dartos fascia. For patients underwent fat grafting, a total of 40-55 ml of fat was injected for penis enlargement. Preoperative and 6-month postoperative data of patients and their partners were collected. The penis diameter, penis appearance score (PAS) and treatment satisfaction scale (TSS) were evaluated. RESULTS: Both pearls implantation (n = 28) and fat grafting (n = 27) led to an increase in penis diameter. The TSS scores of patients who underwent pearls implantation increased by 11.96%, and the partners' scores increased by 9.17%. Specifically, Confidence, Pleasure from Sexual Activity, and Satisfaction with Orgasm scores of partners showed significant improvements. Partners' Satisfaction with Orgasm increased most. The total TSS scores of patients with fat grafting increased by 16.7%; meanwhile, scores of their partners had not obvious improvement. CONCLUSION: Silicone pearls implantation was found to effectively improve the sexual function of men and the sexual satisfaction of their partners compared to fat grafting. Therefore, pearls implantation is possible to enhanced sexual experiences both for man and their partners. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Astrocytic P2X7 receptor regulates depressive-like behavioral reactions of mice in response to acute stressful stimulation.

Acute stress causes depressive-like reactions in the tail suspension (TST) and forced swim tests (FST) of mice. Similarly, inescapable foot shock is able to promote the development of anhedonia as indicated by decreased sucrose consumption of treated mice in the sucrose preference test (SPT). The astrocyte-specific deletion of the P2X7R by a conditional knockout strategy or its knockdown by the intracerebroventricular (i.c.v.) delivery of an adeno-associated virus (AAV) expressing P2X7R-specific shRNA in astrocytes significantly prolonged the immobility time in TST and FST. In contrast, the shRNA-induced downregulation of the P2X7R in neurons, oligodendrocytes, or microglia had no detectable effect on the behavior of treated mice in these tests. Moreover, sucrose consumption in the SPT was not altered following inescapable foot shock treatment in any of these cell type-specific approaches. Immunohistochemistry indicated that the administered astrocyte-specific AAV efficiently conveyed expression of shRNA by hippocampal CA1 astrocytes, but not by neurons. In conclusion, P2X7R in astrocytes of this area of the brain appears to be involved in depressive-like reactions to acute stressors.

Experiences of Certified Peer Support Specialist Providing Formal Peer Support in Mental Health Services: A Systematic Review and Meta-Synthesis.

Peer support specialists (PSSs) in mental healthcare services are individuals recovering from mental health conditions and providing formal peer support to clients with similar conditions. Despite evidence of the benefits of this modality and the increasing demand for it, little is known about the PSSs' experiences in mental healthcare services. This review systematically synthesises available qualitative data on the certified PSSs' experiences in providing formal peer support in mental healthcare services. A search was performed across six electronic databases and one grey literature database for all published and unpublished qualitative studies in English between 2014 and 2022. Mixed-methods studies were included if their qualitative data were extractable. This review included PSSs who provided formal peer support to clients with similar mental health conditions. The included studies were appraised through the Critical Appraisal Skills Program Qualitative checklist, while data extraction was done through a customised tool. Our meta-synthesis revealed an overarching theme on certified PSSs' journey in mental healthcare services, alongside four main themes: (i) emotional impacts of being PSSs, (ii) struggle to justify their roles, (iii) complex roles of PSSs and (iv) sources of support. The review has provided an insightful understanding of the PSSs' roles and needs, for which there is a need to cultivate a supportive working environment. Given the difficulties in adopting the PSSs' roles, as demonstrated by our findings, future research should explore how mental healthcare organisations can address their work-related challenges and cultivate a supportive working environment.