Strontium zinc silicate simultaneously alleviates osteoporosis and sarcopenia in tail-suspended rats via Piezo1-mediated Ca2+ signaling.

Background: Long-term physical inactivity probably leads to a co-existence of osteoporosis and sarcopenia which result in a high risk of falls, fractures, disability and even mortality. However, universally applicable and feasible approaches are lacking in the concurrent treatment of osteoporosis and sarcopenia. In this study, we evaluated the effect of strontium zinc silicate bioceramic (SZS) extract on osteoporosis and sarcopenia and explored its underlying mechanisms. Methods: Hindlimb osteoporosis and sarcopenia were established in a tail-suspended rat model. The bones were conducted µCT scanning, histological examination, and gene expression analysis, and the muscles were conducted histological examination and gene expression analysis. In vitro, the effect of SZS extract on osteoblasts was determined by alizarin red S staining, immunofluorescence and qPCR. Similarly, the effect of SZS extract on myoblasts was determined by immunofluorescence and qPCR.. At last, the role of Piezo1 and the change of intracellular calcium ion (Ca2+) were explored through blockading the Piezo1 by GsMTx4 in MC3T3-E1 and C2C12 cells, respectively. Results: We found that SZS extract could concurrently and efficiently prevent bone structure deterioration, muscle atrophy and fibrosis in hind limbs of the tail-suspended rats. The in vivo study also showed that SZS extract could upregulate the mRNA expression of Piezo1, thereby maintaining the homeostasis of bones and muscles. In vitro study demonstrated that SZS extract could promote the proliferation and differentiation of MC3T3-E1 and C2C12 cells by increasing the intracellular Ca2+ in a Piezo1-dependent manner. Conclusion: This study demonstrated that SZS extract could increase Piezo1-mediated intracellular Ca2+, and facilitate osteogenic differentiation of osteoblast and myogenic differentiation of myoblasts, contributing to alleviation of osteoporosis and sarcopenia in a tail-suspended rat model. The translational potential of this article: The current study might provide a universally applicable and efficient strategy to treat musculoskeletal disorders based on bioactive ceramics. The verification of the role of Piezo1-modulated intracellular Ca2+ during osteogenesis and myogenesis provided a possible therapeutic target against mechanical related diseases.

In vitro simulated digestion and fermentation behaviors of polysaccharides from Pleurotus cornucopiae and their impact on the gut microbiota.

This study investigated the physicochemical characteristics and fermentative behavior between original polysaccharides (PCPs) and polysaccharides extracted after microwave cooking (MPCPs) from Pleurotus cornucopiae during simulated digestion and fecal fermentation. The results revealed notable physicochemical differences between of PCPs and MPCPs. MPCPs exhibited a higher total carbohydrate content, with an increased proportion of glucose. Additionally, MPCPs showed a lower molecular weight (MW) and, a blue shift in Fourier transform infrared spectroscopy (FT-IR). Digestion has a minimal effect on the physicochemical and structural characteristics of PCPs and MPCPs. Within the first 6 h of fermentation, the gut microbiota showed significantly higher utilization of MPCPs. However, PCPs were consumed faster and surpassed MPCPs later. After 24 h, both PCPs and MPCPs were degraded and utilized by the gut microbiota, showing an increased abundance of Firmicutes and Bacteroidota. PCPs excelled in promoting beneficial gut microbiota, such as Phascolarctobacterium, Megamonas, and Bacteroides. Conversely, MPCPs demonstrated a stronger ability to inhibit the growth of harmful opportunistic pathogenic gut microbiota, such as Fusobacterium and Parasutterella. In addition, the content of acetic, propionic, and butyric acids increased significantly in both PCPs and MPCPs. These findings highlight the potential of Pleurotus cornucopiae polysaccharides as prebiotics for intestinal homeostasis.

Six Species of Phyllachora with Three New Taxa on Grass from Sichuan Province, China.

Phyllachora (Phyllachoraceae, Phyllachorales) species are parasitic fungi with a wide global distribution, causing tar spots on plants. In this study, we describe three newly discovered species: Phyllachora chongzhouensis, Phyllachora neidongensis, and Phyllachora huiliensis from Poaceae in China. These species were characterized using morphological traits and multi-locus phylogeny based on the internal transcribed spacer region (ITS) with the intervening 5.8S rRNA gene, the large subunit of the rRNA gene (LSU), and the 18S ribosomal RNA gene (SSU). Three known species of P. chloridis, P. graminis, and P. miscanthi have also been redescribed, because, in reviewing the original references of P. chloridis, P. graminis, and P. miscanthi, these were found to be relatively old and in Chinese or abbreviated. In addition, the illustrations were simple. In molecular identification, the ITS sequence is short, while the ITS, LSU, and SSU are incomplete. Therefore, this study provides new important references for the redescription of three known species and provides further evidence for the identification of new taxa.

Combination Therapy Consisting of Transarterial Chemoembolization, Lenvatinib, and Programmed Cell Death Protein 1 Blockade for Hepatocellular Carcinoma with Inferior Vena Cava Tumor Thrombus: A Case Series Study and Literature Review.

INTRODUCTION: Patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving the blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied. METHODS: In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed. RESULTS: The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and 1 patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in 1 and 3 patients, respectively. Treatment-related adverse events of any grade occurred in 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in 1 patient. CONCLUSION: The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects.

Anti-TNFα in inflammatory bowel disease: from originators to biosimilars.

The introduction of anti-tumor necrosis factor α (TNFα) biologics significantly innovated inflammatory bowel disease (IBD) treatment and increased medical costs. The recent expiration of patents of some anti-TNFα biologics (such as infliximab and adalimumab) facilitated the development of biosimilars. Comparable pharmacokinetic, efficacy, safety, and immunogenicity profiles between anti-TNFα originators and biosimilars were demonstrated in different studies. Anti-TNFα biosimilars hold promise for reducing the high cost of biologics and increasing patient access to biologics. In this review, we outline the current data on the use of anti-TNFα originators and biosimilars in patients with IBD, with a focus on the efficacy, safety, and immunogenicity profiles of infliximab and adalimumab biosimilars. The potential benefits, challenges, and future directions of anti-TNFα biosimilars are also discussed in the review.

Long-term quality of life and influencing factors in elderly patients after vertebroplasty based on the EQ-5D-3L Chinese utility scoring system: a retrospective study.

BACKGROUND: The quality of life of elderly patients after vertebroplasty is influenced by various factors. Although the EuroQol 5-Dimension 3-Level (EQ-5D-3L) scale has been widely used to assess quality of life, the factors affecting the long-term postoperative quality of life of elderly vertebroplasty patients in China have not been thoroughly studied. METHODS: This retrospective study included 519 patients aged 65 years and older who underwent elective vertebroplasty. We collected baseline data from these patients and conducted telephone follow-ups 12 months postoperation to evaluate their EQ-5D-3L health utility scores and EuroQol Visual Analogue Scale (EQ-VAS) scores. Univariate and multivariate linear regression models were used to analyse the factors affecting quality of life. RESULTS: Of the 519 patients, the majority were female (78.0%), aged 65 to 95 years, with an average age of 75.2 years. Twelve months postoperation, pain/discomfort was the most commonly reported issue for 68.4% of patients. The median EQ-5D-3L health utility score was 0.783, with a range between 0.450 and 0.887; the median EQ-VAS score was 75, ranging from 60 to 85. Multivariate linear regression analysis indicated that older age, hormone use, higher American Society of Anesthesiologists (ASA) grades, nondrinking habits, and low albumin levels were found to be independent risk factors affecting long-term quality of life in elderly patients after vertebroplasty. Additionally, a history of tumours, the number of vertebral compression fractures, and bone mineral density were also crucial influencing factors. CONCLUSIONS: Based on the use of the EQ-5D-3L Chinese utility scoring system, we evaluated the quality of life of patients aged 65 and above 12 months after vertebroplasty. This study identified several factors related to postoperative quality of life in elderly vertebroplasty patients, providing crucial evidence for further clinical decisions and patient education.

Integrated bioinformatics analysis of nucleotide metabolism based molecular subtyping and biomarkers in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD), a predominant subtype of non-small cell lung cancers, continues to challenge treatment outcomes due to its heterogeneity and complex tumor microenvironment (TME). Dysregulation in nucleotide metabolism has been identified as a significant factor in tumorigenesis, suggesting its potential as a therapeutic target. Methods: This study analyzed LUAD samples from The Cancer Genome Atlas (TCGA) using Non-negative Matrix Factorization (NMF) clustering, Weighted Correlation Network Analysis (WGCNA), and various machine learning techniques. We investigated the role of nucleotide metabolism in relation to clinical features and immune microenvironment through large-scale data analysis and single-cell sequencing. Using in vivo and in vitro experiments such as RT-qPCR, Western Blot, immunohistochemistry, and subcutaneous tumor formation in mice, we further validated the functions of key nucleotide metabolism genes in cell lines and animals. Results: Nucleotide metabolism genes classified LUAD patients into two distinct subtypes with significant prognostic differences. The 'C1' subtype associated with active nucleotide metabolism pathways showed poorer prognosis and a more aggressive tumor phenotype. Furthermore, a nucleotide metabolism-related score (NMRS) calculated from the expression of 28 key genes effectively differentiated between patient outcomes and predicted associations with oncogenic pathways and immune responses. By integrating various immune infiltration algorithms, we delineated the associations between nucleotide metabolism signature genes and the tumor microenvironment, and characterized their distribution differences at the cellular level by analyzing single-cell sequencing dataset related to immunochemotherapy. Finally, we demonstrated the differential expression of the key nucleotide metabolism gene AUNIP acts as an oncogene to promote LUAD cell proliferation and is associated with tumor immune infiltration. Conclusion: The study underscores the pivotal role of nucleotide metabolism in LUAD progression and prognosis, highlighting the NMRS as a valuable biomarker for clinical outcomes and therapeutic responses. Specifically, AUNIP functions as a critical oncogene, offering a promising target for novel treatment strategies in LUAD.

Effects of tibolone combined with zoledronic acid on bone density, bone metabolism, and pain in postmenopausal patients with osteoporosis.

OBJECTIVE: To explore the efficacy and safety of tibolone combined with zoledronic acid in the treatment of postmenopausal osteoporosis (PMO). METHODS: We conducted a retrospective analysis of 121 PMO patients from March 2019 to July 2021. Patients were divided into two groups based on treatment regimen: an observation group (n=62) receiving zoledronic acid combined with tibolone and a control group (n=59) receiving tibolone monotherapy. We evaluated and compared therapeutic efficacy, bone mineral density, bone metabolism markers (osteocalcin, serum C-terminal telopeptide of type I collagen, and bone alkaline phosphatase), pain, knee joint function, incidence of fragility fractures, and adverse reactions. Logistic regression analysis was used to evaluate risk factors affecting treatment efficacy. RESULTS: The observation group showed a significantly higher therapeutic effect (96.77%) compared to the control group (83.05%), and a lower incidence of fragility fractures (P=0.012). Before treatment, there were no significant differences in bone mineral density, bone metabolism markers, pain status, or knee function between the two groups (all P>0.05). However, after treatment, evaluations showed marked improvements in these parameters in both groups, with more significant enhancements observed in the observation group (all P<0.001). The incidence of adverse reactions did not significantly differ between the groups (20.97% vs 13.56%, P=0.282). Logistic regression analysis identified the use of tibolone combined with zoledronic acid as a protective factor for effective treatment. CONCLUSIONS: Tibolone combined with zoledronic acid significantly increases bone mineral density, improves bone metabolism, and reduces pain in PMO patients, with a safety profile comparable to that of monotherapy. This regimen should be considered for clinical use in treating PMO.

Barriers and facilitators of screening postpartum depression by primary maternal health workers: A mixed methods study based on the normalization process theory.

BACKGROUND: Postpartum depression (PPD) significantly impacts mothers and children's health. China aims to incorporate PPD screening in postpartum home visits, but research on implementation barriers and facilitators is scarce. We designed and implemented a new PPD screening program in Changsha, China, requiring maternal health workers to integrate PPD screening into their postpartum home visits. AIMS: To identify real-world barriers and facilitators associated with integrating PPD screening into routine home visits from the perspective of maternal health workers. METHODS: We employed a mixed-methods approach. Maternal health workers involved in the newly introduced PPD screening program were included. Guided by Normalization Process Theory (NPT), quantitative data were collected using the NoMAD instrument, and qualitative data were obtained through semi-structured interviews. Data were analyzed using descriptive statistics for the survey and thematic analysis for the interviews. RESULTS: All 42 maternal health workers involved in the new PPD program completed the quantitative survey, and nine participated in qualitative interviews. The NoMAD survey revealed high scores for Coherence and Cognitive Participation, but lower scores for Collective Action, particularly regarding insufficient skills and resource adequacy. Thematic analysis identified several barriers, including workload concerns, the need for enhanced psychological healthcare capacity, and lack of economic incentives. Facilitators included the integration of structured feedback and clear referral pathways. CONCLUSION: Addressing identified barriers through targeted skill training, well-defined referral pathways, and formal recognition of the screening program in performance evaluations could help achieve successful normalization.

Aflatoxin B1 decreased flesh flavor and inhibited muscle development in grass carp (Ctenopharyngodon idella).

In nature, aflatoxins, especially aflatoxin B1 (AFB1), are the common mycotoxins, which cause serious health problems for humans and animals. This paper aimed to study the effects of AFB1 on flesh flavor and muscle development of grass carp (Ctenopharyngodon idella) and its mechanism. There were 1440 individual fish in total, with 6 treatments and each treatment replicated 3 times. The 6 treatments were fed a control diet with different doses of AFB1 (0.04, 29.48, 58.66, 85.94, 110.43 and 146.92 µg/kg diet) for 60 d. AFB1 increased myofiber diameter, as well as decreased myofiber density of grass carp muscle (P < 0.05). The contents of free amino acid decreased gradually (P < 0.05) as dietary AFB1 increased in the muscle of grass carp. The levels of reactive oxygen species, malonaldehyde and protein carbonyl (PC) were increased (P < 0.05) with the dietary AFB1 increased. The levels of antioxidant enzyme (glutathione peroxidase, glutathione, glutathione reductase, total antioxidant capacity, anti-superoxide anion, and anti-hydroxyl radical) were decreased (P < 0.05) with the dietary AFB1 increased. In addition, dietary AFB1 decreased the content of collagen, and downregulated the mRNA and protein levels of transforming growth factor-ß (TGF-ß)/Smads signaling pathway in grass carp muscle (P < 0.05). The mRNA and protein levels of myogenic regulatory factors were downregulated in grass carp muscle (P < 0.05). Furthermore, the activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were increased (P < 0.05), and the protein levels of phosphorylate-38 mitogen-activated protein kinase (p-p38MAPK), phosphorylate-c-Jun N-terminal kinase, urokinase-type plasminogen activator (uPA), MMP-2 and MMP-9 were upregulated (P < 0.05), but collagen Ⅰ, laminin ß1 and fibronectin were downregulated (P < 0.05) with the dietary AFB1 increased in the muscle of grass carp. Based on the results of this study, we can draw the following conclusion: dietary AFB1 might damage flesh flavor and inhibit the muscle development through MAPK/uPA/MMP/extracellular matrix (ECM) signaling pathway in grass carp. Moreover, the recommended safe limit of AFB1 in feed is no more than 26.77 µg/kg diet according to the PC levels in grass carp muscle.

Hippocampal Glutamate Levels and Their Correlation With Subregion Volume in School-Aged Children With MRI-Negative Epilepsy: A Preliminary Study.

BACKGROUND: Abnormal levels of glutamate constitute a key pathophysiologic mechanism in epilepsy. The use of glutamate chemical exchange saturation transfer (GluCEST) imaging to measure glutamate levels in pediatric epilepsy is rarely reported in research. PURPOSE: To investigate hippocampal glutamate level variations in pediatric epilepsy and the correlation between glutamate and hippocampal subregional volumes. STUDY TYPE: Cross-sectional, prospective. SUBJECTS: A total of 38 school-aged pediatric epilepsy patients with structurally normal MRI as determined by at least two independent radiologists (60% males; 8.7 ± 2.5 years; including 20 cases of focal pediatric epilepsy [FE] and 18 cases of generalized pediatric epilepsy [GE]) and 17 healthy controls (HC) (41% males; 9.0 ± 2.5 years). FIELD STRENGTH/SEQUENCE: 3.0 T; 3D magnetization prepared rapid gradient echo (MPRAGE) and 2D turbo spin echo GluCEST sequences. ASSESSMENT: The relative concentration of glutamate was calculated through pixel-wise magnetization transfer ratio asymmetry (MTRasym) analysis of the GluCEST data. Hippocampal subfield volumes were computed from MPRAGE data using FreeSurfer. STATISTICAL TESTS: This study used t tests, one-way analysis of variance, Kruskal-Wallis tests, and Pearson correlation analysis. P < 0.05 was considered statistically significant. RESULTS: The MTRasym values of both the left and right hippocampi were significantly elevated in GE (left: 2.51 ± 0.23 [GE] vs. 2.31 ± 0.12 [HCs], right: 2.50 ± 0.22 [GE] vs. 2.27 ± 0.22 [HCs]). The MTRasym values of the ipsilateral hippocampus were significantly elevated in FE (2.49 ± 0.28 [ipsilateral] vs. 2.29 ± 0.16 [HCs]). The MTRasym values of the ipsilateral hippocampus were significantly increased compared to the contralateral hippocampus in FE (2.49 ± 0.28 [ipsilateral] vs. 2.35 ± 0.34 [contralateral]). No significant differences in hippocampal volume were found between different groups (left hippocampus, P = 0.87; right hippocampus, P = 0.87). DATA CONCLUSION: GluCEST imaging have potential for the noninvasive measurement of glutamate levels in the brains of children with epilepsy. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Experimental and DFT calculation study on the efficient removal of high fluoride wastewater from metallurgical wastewater by kaolinite.

Fluoride pollution and water scarcity are urgent issues. Reducing fluoride concentration in water is crucial. Kaolinite has been used to study adsorption and fluoride removal in water and to characterize material properties. The experimental results showed that the adsorption capacity of kaolinite decreased with increasing pH. The highest adsorption of fluoride occurred at pH 2, with a capacity of 11.1 mg/g. The fluoride removal efficiency remained high after four regeneration cycles. The fitting results with the Freundlich isotherm model and the external diffusion model showed that the non-homogeneous adsorption of kaolinite fit the adsorption behavior better. Finally, the adsorption mechanism was analyzed by FT-IR and XPS. The binding energies of various adsorption sites and the chemical adsorption properties of atomic states were discussed in relation to DFT calculations. The results showed that Al and H sites were the main binding sites, and the bonding stability for different forms of fluoride varies, with the size of Al-F (-7.498 eV) > H-F (-6.04 eV) > H-HF (-3.439 eV) > Al-HF (-3.283 eV). Furthermore, the density of states and Mulliken charge distribution revealed that the 2p orbital of F was found to be active in the adsorption process and was the main orbital for charge transfer.

Isotope Evidence for Rice Accumulation of Newly Deposited and Soil Legacy Cadmium: A Three-Year Field Study.

Biogeochemical processes of atmospherically deposited cadmium (Cd) in soils and accumulation in rice were investigated through a three-year fully factorial atmospheric exposure experiment using Cd stable isotopes and diffusive gradients in thin films (DGT). Our results showed that approximately 37-79% of Cd in rice grains was contributed by atmospheric deposition through root and foliar uptake during the rice growing season, while the deposited Cd accounted for a small proportion of the soil pools. The highly bioavailable metals in atmospheric deposition significantly increased the soil DGT-measured bioavailable fraction; yet, this fraction rapidly aged following a first-order exponential decay model, leading to similar percentages of the bioavailable fraction in soils exposed for 1-3 years. The enrichment of light Cd isotopes in the atmospheric deposition resulted in a significant shift toward lighter Cd isotopes in rice plants. Using a modified isotopic mass balance model, foliar and root uptake of deposited Cd accounted for 47-51% and 28-36% in leaves, 41-45% and 22-30% in stems, and 45-49% and 26-30% in grains, respectively. The implications of this study are that new atmospheric deposition disproportionately contributes to the uptake of Cd in rice, and managing emissions thus becomes very important versus remediation of impacted soils.

Mailuo Shutong pills inhibit neuroinflammation by regulating glucose metabolism disorders to protect mice from cerebral ischemia-reperfusion injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Mailuo Shutong Pill (MLST), a traditional Chinese medicine (TCM), has been widely used for clearing heat and detoxifying, eliminating stasis and dredging meridians, dispelling dampness and diminishing swelling. Earlier study found that MLST could improve cerebral ischemic-reperfusion injury, however, the potential mechanism has not been well evaluated. AIM OF STUDY: In this study, a well established and widely used mice model of middle cerebral artery occlusion/reperfusion (MCAO/R) was preformed to evaluate the protective function of MLST on cerebral ischemic-reperfusion injury and further discuss the potential pharmacological mechanisms. MATERIALS AND METHODS: Chemical profiling of MLST was analyzed based on Ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry. ICR mice were challenged by MCAO/R surgery. The protective effect of MLST on MCAO/R injury was evaluated by neurological deficit score, cerebral infarct rate, brain water content, H&E and nissl staining. The blood-brain barrier (BBB) integrity was detected by Evans blue staining. The potential pharmacological mechanism of MLST in treating MCAO/R injury was further elucidated by the methods of proteomics, central carbon targeted metabolomics, as well as Western blot. Immunohistochemistry was used to detect the microglia infiltration, enzyme linked immunosorbent assay (ELISA) kit was explored to evaluate the content of IL-1ß, TNF-α and IL-6 in brain tissue, and Western blot was used to detect proteins expression in brain tissue. RESULTS: A total of 76 chemical compounds have been determined in MLST. MLST effectively protected mice from MCAO/R injury, which was confirmed by lower neurological deficit score, cerebral infarct rate, brain water content and nissl body loss, and improved brain pathology. Meanwhile, MLST upregulated the expression of ZO-1, Occludin and Claudin 5 by downregulating the ratio of TIMP1/MMP9 to suppress the entrance of Evans blue to brain tissue, indicating that MLST maintained the integrity of BBB. Further studies indicated that MLST inhibited the inflammatory level of brain tissue by inhibiting microglia infiltration and downregulating NLRP3 inflammasome signaling pathway. The results of proteomics, Western blot, and central carbon targeted metabolomics confirmed that MLST regulated Glycolysis/Gluconogenesis, Pyruvate metabolism and TCA cycle in brain tissue of mice with MCAO/R. CONCLUSION: MLST inhibits neuroinflammation by regulating glucose metabolism disorders to interfere with immune metabolism reprogramming and inhibit the NLRP3 inflammasome signaling pathway, and finally improve cerebral ischemia-reperfusion injury. This study confirms that MLST is a potential drug for treating Cerebral ischemic stroke.

Disparities in Survival Outcomes Among Patients With Metastatic Melanoma in Texas: Implications for Policy and Interventions in the Era of Immune Checkpoint Inhibitors.

OBJECTIVES: Disparities exist in the length and quality of survival from melanoma. This study evaluated, in a Texas cohort, patient factors associated with melanoma survival and examined if newer immune-oncologic agents extend survival compared with conventional therapies. METHODS: A retrospective analysis of patients diagnosed with metastatic melanoma from 2011 to 2018 in the Texas Cancer Registry database. Multivariable Cox proportional hazard regression was used to evaluate patient characteristics associated with cancer-specific survival (CSS) and overall survival (OS). The patient cohort was then grouped based on receipt of first-line immunotherapy or other therapies. The association between receipt of immunotherapy and survival was assessed with Kaplan-Meier analysis and inverse probability treatment weighted Cox regression. RESULTS: There were 1372 patients with metastatic melanoma. Factors associated with increased melanoma mortality risk (CSS) included being male (HR: 1.13, 95% CI: 1.02-1.26), non-Hispanic black (HR: 1.28, 95% CI: 1.13-1.45), living in poorer counties (HR: 1.40, 95%CI: 1.20-1.64), and having multimorbidity (HR: 1.35, 95% CI: 1.05-1.74). All minority races and Hispanics had poorer OS compared with non-Hispanic Whites. Patients who received first-line immunotherapy had significantly longer median (interquartile range) survival (CSS: 27.00 [21.00 to 42.00] mo vs. 16.00 [14.00 to 19.00] mo; OS: 22.00 [17.00 to 27.00] mo vs. 12.00 [11.00 to 14.00] mo). They also had reduced mortality risk (HR for CSS: 0.80; 95% CI: 0.73-0.88; P<0.0001; HR for OS: 0.76; 95% CI: 0.69-0.83; P<0.0001) compared with the nonimmunotherapy cohort. CONCLUSIONS: This study showed differences in risks from melanoma survival based on patient demographic and clinical characteristics. Low socioeconomic status increased mortality risk, and first-line immunotherapy use favored survival. Health policies and tailored interventions that will promote equity in patient survival and survivorship are essential for managing metastatic melanoma.

Application Effect of 6S Management Mode in Operating Room Nursing.

Background: The nursing work in the operating room is heavy, intensive, and irregular, and the quality of nursing work can directly affect the surgical effect and patient prognosis. Therefore, nursing management in the operating room should be strengthened to protect patients' life safety effectively. Objective: To assess the effectiveness of applying the 6S management model in operating room nursing. Design: This was a retrospective study. Setting: This study was conducted at the Department of Anesthesia Surgery, Nanfang Hospital, Southern Medical University. Participants: The research included 100 operating room nurses on duty between January 2020 and December 2022. Intervention: From January 2020 to June 2021, the hospital conducted routine training programs for nurses in the operating room. From July 2021 to December 2022, the hospital adopted the 6S management model for overseeing nursing work in the operating room. Primary Outcome Measures: (1) nursing quality score (2) nursing staff safety awareness (3) nursing disputes and complaints (4) incidence of adverse reactions (5) patient satisfaction with the quality of nursing care. Results: Following the adoption of the 6S management model, there was a noticeable improvement in the nursing quality scores, the nursing staff's awareness of safety, and the satisfaction levels of patients with the quality of care provided by operation nurses (P < .05). Additionally, the incidence of nursing disputes, complaints, and adverse events among patients decreased significantly compared to before the implementation of 6S (P = .01). Conclusion: Implementing 6S management with a focus on the work of operation room nurses enhanced the competence of the nursing staff and improved management effectiveness, ultimately leading to increased patient satisfaction.

Ion cocktail therapy for myocardial infarction by synergistic regulation of both structural and electrical remodeling.

Myocardial infarction (MI) is a leading cause of death worldwide. Few drugs hold the ability to depress cardiac electrical and structural remodeling simultaneously after MI, which is crucial for the treatment of MI. The aim of this study is to investigate an effective therapy to improve both electrical and structural remodeling of the heart caused by MI. Here, an "ion cocktail therapy" is proposed to simultaneously reverse cardiac structural and electrical remodeling post-MI in rats and minipigs by applying a unique combination of silicate, strontium (Sr) and copper (Cu) ions due to their specific regulatory effects on the behavior of the key cells involved in MI including angiogenesis of endothelial cells, M2 polarization of macrophages and apoptosis of cardiomyocyte. The results demonstrate that ion cocktail treatment attenuates structural remodeling post-MI by ameliorating infarct size, promoting angiogenesis in both peri-infarct and infarct areas. Meantime, to some extent, ion cocktail treatment reverses the deteriorative electrical remodeling by reducing the incidence rate of early/delayed afterdepolarizations and minimizing the heterogeneity of cardiac electrophysiology. This ion cocktail therapy reveals a new strategy to effectively treat MI with great clinical translation potential due to the high effectiveness and safety of the ion cocktail combination.

Systematically altered connectome gradient in benign childhood epilepsy with centrotemporal spikes: Potential effect on cognitive function.

OBJECTIVE: Benign childhood epilepsy with centrotemporal spikes (BECTS) affects brain network hierarchy and cognitive function; however, itremainsunclearhowhierarchical changeaffectscognition in patients with BECTS. A major aim of this study was to examine changes in the macro-network function hierarchy in BECTS and its potential contribution to cognitive function. METHODS: Overall, the study included 50 children with BECTS and 69 healthy controls. Connectome gradient analysis was used to determine the brain network hierarchy of each group. By comparing gradient scores at each voxel level and network between groups, we assessed changes in whole-brain voxel-level and network hierarchy. Functional connectivity was used to detect the functional reorganization of epilepsy caused by these abnormal brain regions based on these aberrant gradients. Lastly, we explored the relationships between the change gradient and functional connectivity values and clinical variables and further predicted the cognitive function associated with BECTS gradient changes. RESULTS: In children with BECTS, the gradient was extended at different network and voxel levels. The gradient scores frontoparietal network was increased in the principal gradient of patients with BECTS. The left precentral gyrus (PCG) and right angular gyrus gradient scores were significantly increased in the principal gradient of children with BECTS. Moreover, in regions of the brain with abnormal principal gradients, functional connectivity was disrupted. The left PCG gradient score of children with BECTS was correlated with the verbal intelligence quotient (VIQ), and the disruption of functional connectivity in brain regions with abnormal principal gradients was closely related to cognitive function. VIQ was significantly predicted by the principal gradient map of patients. SIGNIFICANCE: The results indicate connectome gradient disruption in children with BECTS and its relationship to cognitive function, thereby increasing our understanding of the functional connectome hierarchy and providing potential biomarkers for cognitive function of children with BECTS.

Serum high-density lipoprotein cholesterol levels predict early recurrence and prognosis of intrahepatic cholangiocarcinoma after surgical resection.

Introduction: Dysregulation in lipid metabolism contributes to the occurrence and development of various cancers. The connection between changes in lipid metabolism and the development of intrahepatic cholangiocarcinoma remains uncertain. Our objective was to investigate the significance of blood lipid levels in patients with intrahepatic cholangiocarcinoma who have undergone surgery. Methods: Ninety-seven ICC patients who underwent surgery were retrospectively enrolled. After 92.2 months of follow-up, the Kaplan-Meier analysis and Cox proportional hazard model were used to calculate overall survival and recurrence-free survival. Results: The median age of this cohort was 56 years, and 79 (81.4 %) of them were male. Eighty-eight (90.7 %) patients presented with tumor recurrence and 73 (75.3 %) died. In multivariate analyses, high-density lipoprotein cholesterol level (<0.91 vs. ≥ 0.91 mmol/L, hazard ratio [HR] = 2.55; 95 % CI: 1.38-4.71), lymph node metastasis (Yes vs. No, HR = 2.58; 95 % CI: 1.28-5.19), etiology factor (chronic HBV infection vs. others, HR = 0.5; 95 % CI: 0.28-0.88) and multiple tumor lesions (Yes vs. No, HR = 1.85; 95 % CI: 1.01-3.39) were independent predictors of overall survival. However, only high-density lipoprotein cholesterol level (HR = 1.86; 95 % CI: 1.19-2.92) emerged as the independent factor for recurrence-free survival. High-density lipoprotein cholesterol level (HR = 2.07; 95 % CI: 1.26-3.41), etiology factor (HR = 0.49; 95 % CI: 0.29-0.84), and multiple tumor lesions (HR = 2.00; 95 % CI: 1.14-3.51) were independent predictors of early recurrence. For patients who did not experience the spread of cancer to the lymph nodes, there was a significant correlation between the level of high-density lipoprotein cholesterol and their overall survival, recurrence-free survival, and early recurrence. For patients with low pre-operation high-density lipoprotein cholesterol levels, high post-operation high-density lipoprotein cholesterol levels were associated with better prognosis. Conclusions: Low serum high-density lipoprotein cholesterol level might serve as a sign of poor clinical outcomes (overall survival and recurrence-free survival) and early recurrence among intrahepatic cholangiocarcinoma patients. Strengthening the monitoring and intervention of intrahepatic cholangiocarcinoma patients with poor prognosis might be critical for improving the prognosis.