Genetic deletion of the apoptosis associated speck like protein containing a card in LysM+ macrophages attenuates spinal cord injury by regulating M1/M2 polarization through ASC-dependent inflammasome signaling axis.

Apoptosis associated speck like protein containing a card (ASC), the key adaptor protein of the assembly and activation of canonical inflammasomes, has been found to play a significant role in neuroinflammation after spinal cord injury (SCI). The previous studies indicated that widely block or knockout ASC can ameliorate SCI. However, ASC is ubiquitously expressed in infiltrated macrophages and local microglia, so further exploration is needed on which type of cell playing the key role. In this study, using the LysMcre;Ascflox/flox mice with macrophage-specifc ASC conditional knockout (CKO) and contusive SCI model, we focus on evaluating the specific role of ASC in lysozyme 2 (LysM)+ myeloid cells (mainly infiltrated macrophages) in this pathology. The results revealed that macrophage-specifc Asc CKO exhibited the follow effects: (1) A significant reduction in the numbers of infiltrated macrophages in the all phases of SCI, and activated microglia in the acute and subacute phases. (2) A significant reduction in ASC, caspase-1, interleukin (IL)-1ß, and IL-18 compared to control mice. (3) In the acute and subacute phases of SCI, M1 subset differentiation was inhibited, and M2 differentiation was increased. (4) Histology and hindlimb motor recoveries were improved. In conclusion, this study elucidates that macrophage-specific ASC CKO can improve nerve function recovery after SCI by regulating M1/M2 polarization through inhibiting ASC-dependent inflammasome signaling axis. This indicates that ASC in peripheral infiltrated macrophages may play an important role in SCI pathology, at least in mice, could be a potential target for treatment.

Elevated Risk of Adverse Prognosis in Patients with T2-3 Stage Breast Cancer Exhibiting Non-Pathological Complete Response Following Neoadjuvant Chemotherapy: Significance of Regenerating Islet-Derived Family Member 4.

Objective: In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR). Methods: A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan-Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes. Results: The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06-6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66-3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR. Conclusion: Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.

Injectable Gel-PEG hydrogels as promising delivery system for intravitreal PACAP release: Novel therapeutics for unilateral common carotid artery occlusion induced retinal ischemia.

Retinal ischemia is an ophthalmic emergency often caused by cardiovascular diseases, leading to irreversible vision loss and even blindness. Innovative retinal ischemia treatments are needed due to limited options. The pathological mechanisms involve retinal cell apoptosis and microglial activation. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a well distributed neuropeptide found in both central nervous system and peripheral organs. Though it shows great anti-apoptosis and anti-microglia activation properties, it is rapidly cleared by intravitreal injection. Herein, we established a novel poly(ethylene glycol) (PEG) hydrogel system by cross-linking 4arm-PEG-NHS and 4arm-PEG-NH2 to load PACAP (PACAP@Gel-PEG), which exhibited great fluidity, injectability, structural recovery ability, moderate swelling ratio and drug release ability that were appropriate for drug delivery. Then the safety and effectiveness of the PACAP@Gel-PEG were evaluated in vitro in three retinal cell lines (ARPE-19, 661 W and rRMC) and in vivo using the unilateral common carotid artery occlusion (UCCAO) mice model. The CCK-8 test and live/dead staining demonstrated that PACAP@Gel-PEG exhibited excellent biocompatibility in three retinal cell lines. Furthermore, after PACAP@Gel-PEG treatment, a great anti-apoptotic effect was observed in cells treated by CoCl2. Application of PACAP@Gel-PEG greatly improved the therapeutic efficacy of PACAP in restoring retinal function, maintaining retinal integrity, and suppressing apoptosis and microglia activation in retinal tissues. Moreover, in mice, the biosafety of PACAP@Gel-PEG was confirmed by H&E staining of systemic organs. Taken together, our results demonstrated PACAP@Gel-PEG as a promising therapeutic option for retinal ischemia, providing new strategies for vision restoration.

Clinical value of ACR O-RADS combined with CA125 in the risk stratification of adnexal masses.

Purpose: To develop a combined diagnostic model integrating the subclassification of the 2022 version of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) with carbohydrate antigen 125 (CA125) and to validate whether the combined model can offer superior diagnostic efficacy than O-RADS alone in assessing adnexal malignancy risk. Methods: A retrospective analysis was performed on 593 patients with adnexal masses (AMs), and the pathological and clinical data were included. According to the large differences in malignancy risk indices for different image features in O-RADS category 4, the lesions were categorized into groups A and B. A new diagnostic criterion was developed. Lesions identified as category 1, 2, 3, or 4A with a CA125 level below 35 U/ml were classified as benign. Lesions identified as category 4A with a CA125 level more than or equal to 35 U/ml and lesions with a category of 4B and 5 were classified as malignant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of O-RADS (v2022), CA125, and the combined model in the diagnosis of AMs were calculated and compared. Results: The sensitivity, specificity, PPV, NPV, accuracy, and AUCs of the combined model were 92.4%, 96.5%, 80.2%, 98.8%, 94.1%, and 0.945, respectively. The specificity, PPV, accuracy, and AUC of the combined model were significantly higher than those of O-RADS alone (all P < 0.01). In addition, both models had acceptable sensitivity and NPV, but there were no significant differences among them (P > 0.05). Conclusion: The combined model integrating O-RADS subclassification with CA125 could improve the specificity and PPV in diagnosing malignant AMs. It could be a valuable tool in the clinical application of risk stratification of AMs.

An Overview of Interactions between Goat Milk Casein and Other Food Components: Polysaccharides, Polyphenols, and Metal Ions.

Casein is among the most abundant proteins in milk and has high nutritional value. Casein's interactions with polysaccharides, polyphenols, and metal ions are important for regulating the functional properties and textural quality of dairy foods. To improve the functional properties of casein-based foods, a deep understanding of the interaction mechanisms and the influencing factors between casein and other food components is required. This review started by elucidating the interaction mechanism of casein with polysaccharides, polyphenols, and metal ions. Thermodynamic incompatibility and attraction are the fundamental factors in determining the interaction types between casein and polysaccharides, which leads to different phase behaviors and microstructural types in casein-based foods. Additionally, the interaction of casein with polyphenols primarily occurs through non-covalent (hydrogen bonding, hydrophobic interactions, van der Waals forces, and ionic bonding) or covalent interaction (primarily based on the oxidation of proteins or polyphenols by enzymatic or non-enzymatic (alkaline or free radical grafting) approaches). Moreover, the selectivity of casein to specific metal ions is also introduced. Factors affecting the binding of casein to the above three components, such as temperature, pH, the mixing ratio, and the fine structure of these components, are also summarized to provide a good foundation for casein-based food applications.

Network pharmacology and molecular dynamics study of the effect of the Astragalus-Coptis drug pair on diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The Astragalus-Coptis drug pair is frequently employed in the management of DKD. However, the precise molecular mechanism underlying its therapeutic effect remains elusive. AIM: To investigate the synergistic effects of multiple active ingredients in the Astragalus-Coptis drug pair on DKD through multiple targets and pathways. METHODS: The ingredients of the Astragalus-Coptis drug pair were collected and screened using the TCMSP database and the SwissADME platform. The targets were predicted using the SwissTargetPrediction database, while the DKD differential gene expression analysis was obtained from the Gene Expression Omnibus database. DKD targets were acquired from the GeneCards, Online Mendelian Inheritance in Man database, and DisGeNET databases, with common targets identified through the Venny platform. The protein-protein interaction network and the "disease-active ingredient-target" network of the common targets were constructed utilizing the STRING database and Cytoscape software, followed by the analysis of the interaction relationships and further screening of key targets and core active ingredients. Gene Ontology (GO) function and Kyoto Ency-clopedia of Genes and Genomes (KEGG) pathway enrichments were performed using the DAVID database. The tissue and organ distributions of key targets were evaluated. PyMOL and AutoDock software validate the molecular docking between the core ingredients and key targets. Finally, molecular dynamics (MD) simulations were conducted to simulate the optimal complex formed by interactions between core ingredients and key target proteins. RESULTS: A total of 27 active ingredients and 512 potential targets of the Astragalus-Coptis drug pair were identified. There were 273 common targets between DKD and the Astragalus-Coptis drug pair. Through protein-protein interaction network topology analysis, we identified 9 core active ingredients and 10 key targets. GO and KEGG pathway enrichment analyses revealed that Astragalus-Coptis drug pair treatment for DKD involves various biological processes, including protein phosphorylation, negative regulation of apoptosis, inflammatory response, and endoplasmic reticulum unfolded protein response. These pathways are mainly associated with the advanced glycation end products (AGE)-receptor for AGE products signaling pathway in diabetic complications, as well as the Lipid and atherosclerosis. Molecular docking and MD simulations demonstrated high affinity and stability between the core active ingredients and key targets. Notably, the quercetin-AKT serine/threonine kinase 1 (AKT1) and quercetin-tumor necrosis factor (TNF) protein complexes exhibited exceptional stability. CONCLUSION: This study demonstrated that DKD treatment with the Astragalus-Coptis drug pair involves multiple ingredients, targets, and signaling pathways. We propose a novel approach for investigating the molecular mechanism underlying the therapeutic effects of the Astragalus-Coptis drug pair on DKD. Furthermore, we suggest that quercetin is the most potent active ingredient and specifically targets AKT1 and TNF, providing a theoretical foundation for further exploration of pharmacologically active ingredients and elucidating their molecular mechanisms in DKD treatment.

Development and validation of a neoadjuvant chemotherapy pathological complete remission model based on Reg IV expression in breast cancer tissues: a clinical retrospective study.

OBJECTIVE: To develop and authenticate a neoadjuvant chemotherapy (NACT) pathological complete remission (pCR) model based on the expression of Reg IV within breast cancer tissues with the objective to provide clinical guidance for precise interventions. METHOD: Data relating to 104 patients undergoing NACT were collected. Variables derived from clinical information and pathological characteristics of patients were screened through logistic regression, random forest, and Xgboost methods to formulate predictive models. The validation and comparative assessment of these models were conducted to identify the optimal model, which was then visualized and tested. RESULT: Following the screening of variables and the establishment of multiple models based on these variables, comparative analyses were conducted using receiver operating characteristic (ROC) curves, calibration curves, as well as net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Model 2 emerged as the most optimal, incorporating variables such as HER-2, ER, T-stage, Reg IV, and Treatment, among others. The area under the ROC curve (AUC) for Model 2 in the training dataset and test dataset was 0.837 (0.734-0.941) and 0.897 (0.775-1.00), respectively. Decision curve analysis (DCA) and clinical impact curve (CIC) further underscored the potential applications of the model in guiding clinical interventions for patients. CONCLUSION: The prediction of NACT pCR efficacy based on the expression of Reg IV in breast cancer tissue appears feasible; however, it requires further validation.

Hepatocellular carcinoma: An analysis of the expression status of stress granules and their prognostic value.

BACKGROUND: Hepatocellular carcinoma (HCC) is a global popular malignant tumor, which is difficult to cure, and the current treatment is limited. AIM: To analyze the impacts of stress granule (SG) genes on overall survival (OS), survival time, and prognosis in HCC. METHODS: The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC), GSE25097, and GSE36376 datasets were utilized to obtain genetic and clinical information. Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach, and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression, respectively. The prognostic model's receiver operating characteristic (ROC) curve was produced and plotted utilizing the time ROC software package. Nomogram models were constructed to predict the outcomes at 1, 3, and 5-year OS prognostications with good prediction accuracy. RESULTS: We identified seven SG genes (DDX1, DKC1, BICC1, HNRNPUL1, CNOT6, DYRK3, CCDC124) having a prognostic significance and developed a risk score model. The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group (P < 0.001). The nomogram model's findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort. Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle, RNA editing, and other biological processes. CONCLUSION: Based on the impact of SG genes on HCC prognosis, in the future, it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.

An isocratic HPLC-UV analytical procedure for assessment of glutathione and its related substances.

Reduced glutathione (GSH) is an endogenous tripeptide antioxidant which plays a crucial role in a variety of physiological and pathological activities. Although GSH is not present in any FDA-approved drug product, GSH dietary supplement products and compounded GSH drugs are available to patients in the US. Several incidents of toxicity have occurred in recent years due to endotoxin or otherwise contaminated GSH in compounded drugs. Efficient and sensitive analytical methods are needed for assessing and ensuring the quality of GSH substance and associated drug or dietary supplement products. Impurities A (L-cysteinylglycine), B (cysteine), C (oxidized L-glutathione) and D (γ-L-glutamyl-L-cysteine) are the main related impurities for GSH drug substance which have been detected and quantified by capillary electrophoresis and qNMR analytical procedures. However, there are no reported HPLC methods for detecting or quantifying the three main related impurities A, B and D even though numerous HPLC analytical methods have been reported for analyzing GSH and impurity C. In this report, an isocratic HPLC-UV analytical procedure was developed and validated for separating and identifying GSH and related impurities A-D as well as a newly identified degradant, L-pyroglutamic acid (pGlu), within 10 minutes with resolution (RS) more than 3. The LOD and LOQ were determined to be 0.02 % w/w and 0.05 % w/w, respectively, for impurities A-D and pGlu. Importantly, the optimized HPLC analytical procedure for GSH assay does not have interference from impurities A, B and D, providing highly specific results compared to the commonly used iodine titration method. The newly validated analytical procedure was applied to assess different commercial GSH bulk substance samples. The results suggest that the analytical procedure described in this work is suitable for quality assessment of GSH samples.

Triglyceride-Glucose Index is an Independent Risk Factor for Hepatocellular Carcinoma Development in Patients with HBV-Related Liver Cirrhosis.

Aim: This study aimed to explore the effects of the triglyceride-glucose (TyG) index on hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV)-related liver cirrhosis (LC). Methods: A total of 242 patients with HBV-related LC were enrolled and followed-up. Logistic regression analysis was performed to investigate risk factors for HCC. Results: The median follow-up time was 37 months (range: 6-123 months). At the end of the follow-up, 11 (11.3%) patients with compensated cirrhosis (CC) and 45 (31.0%) with decompensated cirrhosis (DC) developed HCC. The TyG index was higher in the HCC group than in the non-HCC group (P=0.05). Univariate analysis showed that age (P<0.01), DC (P<0.01), TyG index (P=0.08), albumin (ALB) level (P=0.05), platelet (PLT) count (P<0.01), and HBV DNA positivity (P<0.01) were associated with HCC development. Multivariate analysis revealed that age, DC, TyG index, PLT count, and HBV DNA positivity were independent risk factors for HCC development (P=0.01, 0.01, <0.01, 0.05, and <0.01, respectively). For patients with DC, multivariate logistic regression analysis revealed that age, TyG index, and HBV DNA positivity were independent risk factors for HCC development (all P<0.05). A new model encompassing age, DC, TyG, PLT, and positive HBV DNA had optimal predictive accuracy in patients with DC or CC, with a cutoff value of 0.197. The areas under the receiver operating characteristic curves (AUROCs) of the model for predicting HCC development in patients with LC, DC, and CC were 0.778, 0.721, and 0.783, respectively. Conclusion: TyG index was identified as an independent risk factor for HCC development in patients with LC.

Exosomes derived from vMIP-II-Lamp2b gene-modified M2 cells provide neuroprotection by targeting the injured spinal cord, inhibiting chemokine signals and modulating microglia/macrophage polarization in mice.

Inflammation is one of the key injury factors for spinal cord injury (SCI). Exosomes (Exos) derived from M2 macrophages have been shown to inhibit inflammation and be beneficial in SCI animal models. However, lacking targetability restricts their application prospects. Considering that chemokine receptors increase dramatically after SCI, viral macrophage inflammatory protein II (vMIP-II) is a broad-spectrum chemokine receptor binding peptide, and lysosomal associated membrane protein 2b (Lamp2b) is the key membrane component of Exos, we speculated that vMIP-II-Lamp2b gene-modified M2 macrophage-derived Exos (vMIP-II-Lamp2b-M2-Exo) not only have anti-inflammatory properties, but also can target the injured area by vMIP-II. In this study, using a murine contusive SCI model, we revealed that vMIP-II-Lamp2b-M2-Exo could target the chemokine receptors which highly expressed in the injured spinal cords, inhibit some key chemokine receptor signaling pathways (such as MAPK and Akt), further inhibit proinflammatory factors (such as IL-1ß, IL-6, IL-17, IL-18, TNF-α, and iNOS), and promote anti-inflammatory factors (such as IL-4 and Arg1) productions, and the transformation of microglia/macrophages from M1 into M2. Moreover, the improved histological and functional recoveries were also found. Collectively, our results suggest that vMIP-II-Lamp2b-M2-Exo may provide neuroprotection by targeting the injured spinal cord, inhibiting some chemokine signals, reducing proinflammatory factor production and modulating microglia/macrophage polarization.

Qualitative and quantitative analysis of glutathione and related impurities in pharmaceuticals by qNMR.

In this study, an alternative method to compendial analytical procedures with enhanced detection and separation capabilities was validated for the quality assessment of glutathione (GSH) drug substance. The related impurities A, B, C, and D present in GSH drug substance were characterized using a one-dimension proton nuclear magnetic resonance (1D 1H NMR) method on a 600 MHz spectrometer equipped with a liquid nitrogen cryoprobe. Two sample preparations at different pH were optimized to ensure the unambiguous identification of different impurities in the GSH samples. Specifically, impurities A and C in a GSH sample can be tested at pH 3.0, while pH 7.4 is more suitable for testing impurities B and D. The quantitative NMR (qNMR) method was validated following International Council for Harmonisation (ICH) guidelines. The limit of detection (LOD) was less than 0.1% wt for an individual impurity, and the limit of quantitation (LOQ) ranged from 0.14 to 0.24% wt, using about 14 min experimental time per spectrum. Following validation, the qNMR method was applied to assess different commercial GSH bulk substance samples, an in-house compounded GSH drug product, and a GSH dietary supplement product. The method was also applied to monitor GSH degradation (hydrolysis and oxidation) over time to provide quantitative information on GSH degradation and stability. The results suggest that the qNMR method can serve as a highly specific and efficient orthogonal tool for assessing the quality of GSH pharmaceuticals, providing both qualitative and quantitative information on GSH and its related impurities A-D.

Novel Melanocortin-3 and -4 Receptor Functional Variants in Asian Children With Severe Obesity.

CONTEXT: Genetic variants in melanocortin 3 receptor (MC3R) and melanocortin 4 receptor (MC4R) genes are strongly associated with childhood obesity. OBJECTIVE: This study aims to identify and functionally characterize MC3R and MC4R variants in an Asian cohort of children with severe early-onset obesity. METHODS: Whole-exome sequencing was performed to screen for MC3R and MC4R coding variants in 488 Asian children with severe early-onset obesity (body mass index for age ≥97th percentile). Functionality of the identified variants were determined via measurement of intracellular cyclic adenosine monophosphate (cAMP) concentrations and luciferase activity. RESULTS: Four MC3R and 2 MC4R heterozygous nonsynonymous rare variants were detected. There were 3 novel variants: MC3R c.151G > C (p.Val51Leu), MC4R c.127C > A (p.Gln43Lys), and MC4R c.272T > G (p.Met91Arg), and 3 previously reported variants: MC3R c.127G > A (p.Glu43Lys), MC3R c.97G > A (p.Ala33Thr), and MC3R c.437T > A (p.Ile146Asn). Both MC3R c.127G > A (p.Glu43Lys) and MC4R c.272T > G (p.Met91Arg) variants demonstrated defective downstream cAMP signaling activity. The MC4R c.127C > A (p.Gln43Lys) variant showed reduced cAMP signaling activity at low substrate concentration but the signaling activity was restored at high substrate concentration. The MC3R c.151G > C (p.Val51Leu) variant did not show a significant reduction in cAMP signaling activity compared to wild-type (WT) MC3R. Coexpression studies of the WT and variant MC3R/MC4R showed that the heterozygous variants did not exhibit dominant negative effect. CONCLUSION: Our functional assays demonstrated that MC3R c.127G > A (p.Glu43Lys) and MC4R c.272T > G (p.Met91Arg) variants might predispose individuals to early-onset obesity, and further studies are needed to establish the causative effect of these variants in the pathogenesis of obesity.

Correlation between serum vitamin D level and uterine volume in girls with idiopathic central precocious puberty.

OBJECTIVES: Investigate serum vitamin D (vit D) levels' relation to uterine volume in idiopathic central precocious puberty (ICPP) girls and compare findings with normal peers. METHODS: Analyzed 278 ICPP cases from January 2017 to September 2022 alongside 239 normally developing girls. Collected clinical data and lab markers and performed subgroup analysis based on vit D levels. Correlation and regression analyses were conducted. RESULTS: The ICPP group exhibited elevated uterine volume and lower serum vit D compared to controls (p<0.05). A weak negative correlation was noted between vit D and uterine volume in ICPP (r=-0.193, p=0.004), and no such correlation in controls (r=-0.073, p=0.319). The ICPP vit D deficiency subgroup displayed higher uterine volume than the insufficiency and sufficiency subgroups (p<0.05). Uterine volume in the insufficiency subgroup exceeded the sufficiency subgroup (p<0.05). After adjusting for confounders, lower vit D is linked to increased ICPP uterine volume (non-standardized regression coefficient ß=-25.55, 95 % CI= -46.23, -4.87, p=0.016). A Limited correlation between vit D and uterine volume was seen in girls with normal pubertal timing. CONCLUSIONS: We demonstrated a correlation between vit D and uterine volume in ICPP girls, absent in normal peers. ICPP girls often exhibit lower vit D levels and increased uterine volume. Further research is vital for understanding vit D's role in ICPP pathogenesis and guiding prevention and treatment strategies.

Building bridges of excellence: a comprehensive competence framework for nurses in hospice and palliative care-a mixed method study.

BACKGROUND: Hospice and Palliative Care (HPC) is in high demand in China; however, the country is facing the shortage of qualified HPC nurses. A well-suited competence framework is needed to promote HPC human resource development. Nevertheless, existing unstandardized single-structured frameworks may not be sufficient to meet this need. This study aimed at constructing a comprehensive multi-structured HPC competence framework for nurses. METHODS: This study employed a mixed-method approach, including a systematic review and qualitative interview for HPC competence profile extraction, a two-round Delphi survey to determine the competences for the framework, and a cross-sectional study for framework structure exploration. The competence profiles were extracted from publications from academic databases and interviews recruiting nurses working in the HPC field. The research team synthesized profiles and transferred them to competences utilizing existing competence dictionaries. These synthesized competences were then subjected to Delphi expert panels to determine the framework elements. The study analyzed theoretical structure of the framework through exploratory factor analysis (EFA) based on a cross-sectional study receiving 491 valid questionnaires. RESULTS: The systematic review involved 30 publications from 10 countries between 1995 and 2021, while 13 nurses from three hospitals were interviewed. In total, 87 and 48 competence profiles were respectively extracted from systematic review and interview and later synthesized into 32 competences. After the Delphi survey, 25 competences were incorporated into the HPC competence framework for nurses. The EFA found a two-factor structure, with factor 1 comprising 18 competences namely Basic Competences; factor 2 concluding 7 competences namely Developmental Competences. CONCLUSIONS: The two-factor HPC competence framework provided valuable insights into the need and directions of Chinese HPC nurses' development.

[Analysis of the difference in metabolites and gene expressions between pre-receptive and receptive endometria].

OBJECTIVE: To analyze the difference in the gene expression, amino acid and carnitine levels in the cervical secretions between the endometria of pre-receptive and receptive stages, with an aim to provide clues for identifying new molecular markers for endometrial receptivity. METHODS: Fifty nine infertile women treated at the Department of Reproductive Medicine of Linyi People's Hospital from January 6, 2020 to January 31, 2022 were selected as as the study subjects, which were matched with 3 pairs (6 cases) of infertile women preparing for embryo transfer based on factors such as age, body mass index, and length of infertility. Endometrial tissue samples were collected for gene transcription and expression analysis. Twenty five women who had become pregnant through assisted reproductive technology were selected as the control group, and 28 non-pregnant women receiving ovulation monitoring at the Outpatient Department were enrolled as the case group. Status of endometrial receptivity was determined by ultrasonography. In the former group, endometrial tissues were sampled for sequencing, and GO and KEGG database enrichment analysis of differentially expressed genes was carried out. In the latter group, cervical secretions were collected, and amino acid and carnitine levels were measured by mass spectrometry. Statistical analysis was carried out using rank sum test, t test and chi-square test with SPSS v25.0 software. RESULTS: No difference was found in the clinical data of the patients with regard to age, body mass index, infertility years, AMH, FSH, LH, E2, and type of infertility. Compared with the receptive endometrial tissues, there were 100 significantly up-regulated genes and 191 significantly down-regulated genes in the pre-receptive endometrial tissue, with the most significantly altered ones being HLA-DRB5 and MMP10. The biological processes, molecular functions and pathways enriched by more differentially expressed genes in GO and KEGG were mainly immune regulation, cell adhesion and tryptophan metabolism. Analysis of secretion metabolism also revealed a significant difference in the levels of amino acids and carnitine metabolites between the two groups (P < 0.05), in particular those of Alanine, Valine, 3-hydroxybutyrylcarnitine (C4OH) + malonylcarnitine (C3DC)/captoylcarnitine (C10). CONCLUSION: A significant difference has been discovered in the levels of gene transcription and protein expression in the endometrial tissues from the pre-receptive and receptive stages. The levels of amino acids and carnitine, such as Alanine, Valine, 3-hydroxybutyryl carnitine (C4OH)+malonyl carnitine (C3DC)/caproyl carnitine (C10), may be associated with the receptive status of the endometrium, though this need to be verified with larger samples.

Magnetic anchor technique assisted endoscopic submucosal dissection for early esophageal cancer.

BACKGROUND: Esophageal cancer has high incidence globally and is often diagnosed at an advanced stage. With the widespread application of endoscopic technologies, the need for early detection and diagnosis of esophageal cancer has gradually been realized. Endoscopic submucosal dissection (ESD) has become the standard of care for managing early tumors of the esophagus, stomach, and colon. However, due to the steep learning curve, difficult operation, and technically demanding nature of the procedure, ESD has currently been committed to the development of various assistive technologies. AIM: To explore the feasibility and applicability of magnetic anchor technique (MAT)-assisted ESD for early esophageal cancer. METHODS: Isolated pig esophagi were used as the experimental model, and the magnetic anchor device was designed by us. The esophagi used were divided into two groups, namely the operational and control groups, and 10 endoscopists completed the procedure. The two groups were evaluated for the following aspects: The total operative time, perforation rate, rate of whole mucosal resection, diameter of the peering mucosa, and scores of endoscopists' feelings with the procedure, including the convenience, mucosal surface exposure degree, and tissue tension. In addition, in the operational group, the soft tissue clip and the target magnet (TM) were connected by a thin wire through a small hole at the tail end of the TM. Under gastroscopic guidance, the soft tissue clip was clamped to the edge of the lesioned mucosa, which was marked in advance. By changing the position of the anchor magnet (AM) outside the esophagus, the pulling force and pulling direction of the TM could be changed, thus exposing the mucosal peeling surface and assisting the ESD. RESULTS: Herein, each of the two groups comprised 10 isolated esophageal putative mucosal lesions. The diameter of the peering mucosa did not significantly differ between the two groups (2.13 ± 0.06 vs 2.15 ± 0.06, P = 0.882). The total operative time was shorter in the operational group than in the control group (17.04 ± 0.22 min vs 21.94 ± 0.23 min, P < 0.001). During the entire experiment, the TM remained firmly connected with the soft tissue clip and did not affect the opening, closing, and release of the soft tissue clip. The interaction between the TM and AM could provide sufficient tissue tension and completely expose the mucosa, which greatly assists the surgeon with the operation. There was no avulsion of the mucosa, and mucosal lesions were intact when peeled. Therefore, the scores of endoscopists' feelings were higher in the operational group than in the control group in terms of the convenience (9.22 ± 0.19 vs 8.34 ± 0.15, P = 0.002), mucosal surface exposure degree (9.11 ± 0.15 vs 8.25 ± 0.12, P < 0.001), and tissue tension (9.35 ± 0.13 vs 8.02 ± 0.17, P < 0.001). The two groups did not significantly differ in the perforation rate and rate of whole mucosal resection. CONCLUSION: We found MAT-assisted ESD safe and feasible for early esophageal cancer. It could greatly improve the endoscopic operation experience and showed good clinical application prospects.

Global trends and current status in pheochromocytoma: a bibliometric analysis of publications in the last 20 years.

Objective: Pheochromocytoma is a rare catecholamine-producing neuroendocrine tumour originating from the chromaffin cells of the adrenal medulla or extra-adrenal paraganglia. However, there are few bibliometric studies on Pheochromocytoma. Therefore, this study was employed to summarize the global trends and current status in pheochromocytoma by bibliometric analysis. Materials and methods: The Web of Science (WOS) core collection database was searched for publications relating to pheochromocytoma from 2001 to 2021. Bibliometric analysis was used to examine the data, and Microsoft Excel was utilized to create bar graphs. In addition, VOSviewer was used to carry out co-authorship analysis, co-citation analysis and co-occurrence analysis. CiteSpace was used to analyze the keywords citation bursts. Results: A total of 8,653 publications published in 1,806 journals by 38,590 authors in 6,117 organizations from 100 countries/regions were included in our study. Among them, USA was the leading countries in terms of total publications and sum of time cited, whereas Eunice Kennedy Shriver Natl Inst Child Hlth & Hum was the leading institutions. The main publications for pheochromocytoma-related articles were Journal of clinical endocrinology &metabolism. Pacak karel and Eisenhofer Graeme were the main contributing authors. The studies on pheochromocytoma could be grouped into five clusters: Treatment, Mechanism, Etiology, Radiology and Hormones study. Moreover, the radiology study, etiology study and some specific keywords such germlines mutation, mesenchymal stem-cells, autophagy, neuroinflammation, neurotoxicity, and hemodynamic instability, may become the hot spots of future. Conclusion: Although the number of articles on pheochromocytoma has fluctuated slightly over the past 20 years, there has been an overall upward trend. In general, precision medicine research on pheochromocytoma, especially metastatic pheochromocytoma, in terms of diagnosis, treatment, and etiology will be a hot research topic in the future. This study helps to understand the research perspectives, hot spots and trends of pheochromocytoma and provide new insight and a basis for future pheochromocytoma research quickly.

Novel deformable self-assembled magnetic anastomosis ring for endoscopic treatment of colonic stenosis via natural orifice.

BACKGROUND: Although endoscope-assisted magnetic compression anastomosis has already been reported for colonic anastomosis, there is no report on a single-approach operation using the natural orifice. AIM: To design a deformable self-assembled magnetic anastomosis ring (DSAMAR) for colonic anastomosis for use in single-approach operation and evaluate its feasibility and safety through animal experiments. METHODS: The animal model for colonic stenosis was prepared by partial colonic ligation in eight beagles. The magnetic compression anastomosis of their colonic stricture was performed by endoscopically assisted transanal implantation of the DSAMAR. The anastomotic specimen, obtained 2 wk after the operation, was observed by both the naked eye and a light microscope. RESULTS: The DSAMAR was successfully inserted into the proximal end of colon stenosis through the anus. The DSAMAR of seven dogs was successfully transformed into rings, while that of the remaining dog was removed after the first deformation failed. The rings were successfully retransformed after optimization. All animals underwent colonic anastomosis using the DSAMAR. No device-related or procedure-related adverse events were observed. The colostomy specimens of the experimental dogs were obtained 2 wk after the operation. Both gross and histological observations showed good anastomotic healing. CONCLUSION: The DSAMAR is a safe and feasible option for the treatment of colon stenosis. Its specific deformation and self-assembly capability maximize the applicability of the minimally invasive treatment.

Clinicopathological correlations of peritoneal endometriosis and deep infiltrating endometriosis.

OBJECTIVE: The present study aims to investigate the clinical and histopathological features of peritoneal endometriosis (PEM) and deep infiltrating endometriosis (DIE). METHODS: A total of 100 patients with PEM and DIE admitted to Dalian Women and Children's Hospital/Dalian Women and Children's Medical Center between October 2018 and December 2021 were selected as the study subjects. One hundred and thirty-one PEM specimens and 37 DIE were collected, 22 cases of these patients' eutopic endometrium were used as control (15 in PEM, seven in DIE). The present study mainly analysed the pelvic distribution, the histopathological and immunohistochemical features and peritoneal invasion of PEM and DIE. RESULTS: The main distribution of PEM and DIE was located in the posterior pelvic cavity (p < .001). The histopathological characteristics of different PEM forms were different: the contents of endometrioid glands, endometrioid stroma, smooth muscle, fibrous tissue and blood vessels in different lesions were statistically significant (all p < .050). Estrogen receptor (ER) of PEM and DIE was highly expressed in endometrioid glandular epithelium and endometrioid stroma, without statistical significance (p = .330/.113). Progesterone receptor (PR) was also highly expressed in endometrioid glandular epithelium and endometrioid stroma without statistical significance (p = .757/.798). Ki-67 expression of DIE in endometrioid glandular epithelium was significantly higher than that in brown and white lesions (p < .001), while its expression in the endometrioid stroma was not statistically significant in red lesions (p = .070), but higher than that in other PEM lesions (p < .001). Different morphological lesions had different invasiveness rates and depths of invasion to the peritoneum. White lesions had a deeper subperitoneal invasion level than transparent and vesicular lesions. CONCLUSIONS: Although different morphological appearance of PEM is a degenerative process, some active brown lesions of PEM have invasive effects during the process and may further develop into DIE. PEM and DIE may be different developmental stages of the same disease.

In summary, PEM is a progressive disease, and its different morphological appearance reflects different stages of lesion development.Ectopic endometrial cells have a destructive effect on the peritoneal structures; as the lesion progresses, it continuously infiltrates the subperitoneum.PEM and DIE are different development stages of the same disease. The homology of the two lesions has yet to be explored in terms of pathogenesis.