Analysis of factors influencing vascular calcification in peritoneal dialysis patients and their impact on long-term prognosis.

BACKGROUND: This study aims to investigate the influencing factors of vascular calcification in peritoneal dialysis (PD) patients and its relationship with long-term prognosis. METHODS: This retrospective cohort study included chronic kidney disease patients undergoing peritoneal dialysis at the Peritoneal Dialysis Center of Beijing Luhu Hospital, Capital Medical University, from January 2019 to March 2019. Demographic and clinical laboratory data, including serum sclerostin (SOST), calcium (Ca), phosphate (P), serum albumin (ALB), and intact parathyroid hormone (iPTH) levels, were collected. Abdominal aortic calcification (AAC) was assessed using abdominal lateral X-ray examination to determine the occurrence of vascular calcification, and patients were divided into the AAC group and Non-AAC group based on the results. RESULTS: A total of 91 patients were included in the study. The AAC group consisted of 46 patients, while the Non-AAC group consisted of 45 patients. The AAC group had significantly older patients compared to the non-AAC group (P < 0.001) and longer dialysis time (P = 0.004). Multivariable logistic regression analysis indicated that risk factors for vascular calcification in PD patients included dialysis time, diabetes, hypertension, and SOST. Kaplan-Meier survival analysis showed that the AAC group had a significantly higher mortality rate than the non-AAC group (χ2 = 35.993, P < 0.001). Multivariable Cox regression analysis revealed that dialysis time, diabetes and AAC were risk factors for all-cause mortality in peritoneal dialysis patients. CONCLUSION: Longer dialysis time, comorbid diabetes, comorbid hypertension, and SOST are risk factors for vascular calcification in PD patients. Additionally, AAC, longer dialysis time, and comorbid diabetes are associated with increased risk of all-cause mortality in peritoneal dialysis patients.

Histone H3K18 and Ezrin Lactylation Promote Renal Dysfunction in Sepsis-Associated Acute Kidney Injury.

Histone lactylation is a metabolic stress-related histone modification. However, the role of histone lactylation in the development of sepsis-associated acute kidney injury (SA-AKI) remains unclear. Here, histone H3K18 lactylation (H3K18la) is elevated in SA-AKI, which is reported in this study. Furthermore, this lactate-dependent histone modification is enriched at the promoter of Ras homolog gene family member A (RhoA) and positively correlated with the transcription. Correction of abnormal lactate levels resulted in a reversal of abnormal histone lactylation at the promoter of RhoA. Examination of related mechanism revealed that histone lactylation promoted the RhoA/Rho-associated protein kinase (ROCK) /Ezrin signaling, the activation of nuclear factor-κB (NF-κB), inflammation, cell apoptosis, and aggravated renal dysfunction. In addition, Ezrin can undergo lactylation modification. Multiple lactylation sites are identified in Ezrin and confirmed that lactylation mainly occurred at the K263 site. The role of histone lactylation is revealed in SA-AKI and reportes a novel post-translational modification in Ezrin. Its potential role in regulating inflammatory metabolic adaptation of renal proximal tubule epithelial cells is also elucidated. The results provide novel insights into the epigenetic regulation of the onset of SA-AKI.

Waist subcutaneous soft tissue metastasis of rectal mucinous adenocarcinoma: A case report.

BACKGROUND: Rectal mucinous adenocarcinoma (MAC) is a rare pathological type of rectal cancer with unique pathological features and a poor prognosis. It is difficult to diagnose and treat early because of the lack of specific manifestations in some aspects of the disease. The common metastatic organs of rectal cancer are the liver and lung; however, rectal carcinoma with metastasis to subcutaneous soft tissue is a rare finding. CASE SUMMARY: In this report, the clinical data, diagnosis and treatment process, and postoperative pathological features of a patient with left waist subcutaneous soft tissue masses were retrospectively analyzed. The patient underwent surgical treatment after admission and recovered well after surgery. The final pathological diagnosis was rectal MAC with left waist subcutaneous soft tissue metastasis. CONCLUSION: Subcutaneous soft tissue metastasis of rectal MAC is rare, and it can suggest that the tumor is disseminated, and it can appear even earlier than the primary malignant tumor, which is occult and leads to a missed diagnosis and misdiagnosis clinically. When a subcutaneous soft tissue mass of unknown origin appears in a patient with rectal cancer, a malignant tumor should be considered.

The Role and Potential Mechanisms of Rehabilitation Exercise Improving Cardiac Remodeling.

Rehabilitation exercise is a crucial non-pharmacological intervention for the secondary prevention and treatment of cardiovascular diseases, effectively ameliorating cardiac remodeling in patients. Exercise training can mitigate cardiomyocyte apoptosis, reduce extracellular matrix deposition and fibrosis, promote angiogenesis, and regulate inflammatory response to improve cardiac remodeling. This article presents a comprehensive review of recent research progress, summarizing the pivotal role and underlying mechanism of rehabilitation exercise in improving cardiac remodeling and providing valuable insights for devising effective rehabilitation treatment programs. Graphical Abstract.

Strategic Construction of meso-Aryl-Substituted N,N-Carbonyl-Bridged Dipyrrinones as Small, Bright, and Tunable Fluorophores.

A series of novel N,N-carbonyl-bridged dipyrrinone fluorophores have been directly constructed from α-halogenated dipyrrinones, which are conveniently obtained from the acid-catalyzed hydrolysis of readily available α,α'-dihalodipyrrins. This novel methodology affords efficient modulation of the functional groups at both the meso- and α-positions of this fluorophore. These resultant dyes show tunable absorption and emission wavelengths, good molar absorption coefficients, relatively large Stokes shifts, and excellent fluorescence quantum yields up to 0.99, and have been successfully applied in both one- and two-photon fluorescence microscopy imaging in living cells.

Circ DENND4C inhibits pyroptosis and alleviates ischemia-reperfusion acute kidney injury by exosomes secreted from human urine-derived stem cells.

Acute kidney injury (AKI) is a disease characterised by acute onset, high mortality, and poor prognosis, and is mainly caused by ischemia-reperfusion (I/R). Human urine-derived stem cells (USCs) exhibit antioxidant, anti-inflammatory, and anti-apoptotic cytoprotective effects. Previously, we found that exosomes from USCs had the ability to inhibit apoptosis and protect kidneys from I/R injury. This study aimed to investigate the role of USC-derived exosomes (USC-Exos) in reducing pyroptosis and alleviating I/R-AKI. Models of HK-2 cells hypoxia-reoxygenation (H/R) and I/R kidney injury was established in Sprague Dawley rats to simulate AKI in vitro and in vivo. USC-Exos were isolated using ultracentrifugation and identified via electron microscopy and western blotting. USC-Exos were co-cultured with HK-2 cells and injected into rats via the tail vein. The expression of pyroptosis-related molecules (GSDMD, caspase-1, and NLRP-3) was verified using PCR and western blotting. Changes in renal function were reflected in the serum creatinine, urea, and cystatin C levels. The degree of renal injury was determined using haematoxylin and eosin and immunohistochemical staining. The levels of IL-1ß and IL-18 were detected using enzyme-linked immunosorbent assay (ELISA) to verify the role of USC-Exos in pyroptosis. Differentially expressed circRNAs in I/R rat kidneys were screened by transcriptome sequencing, and a dual-luciferase experiment was used to verify the interaction between upstream and downstream molecules. Ischemia-reperfusion resulted in significantly impaired renal function and expression of pyroptosis molecules, and significantly increased concentrations of inflammatory factors. These effects were reversed by injecting USC-Exos. Circ DENND4C was the most significantly decreased circRNA in I/R rat renal tissue, and knock-down of circ DENND4C can aggravate AKI in vivo and in vitro. DAVID(http://david.abcc.ncifcrf.gov) website showed that miR 138-5p/FOXO3a is a potential downstream target of circ DENND4C. Knock-down of circ DENND4C in HK-2 cells resulted in increased expression of miR 138-5p and increased miR 138-5p can reverse the regulation of FOXO3a. Dual-luciferase assay verified the reverse interaction between circ DENND4C, miR 138-5p, and FOXO3a. Exosomes promote cell proliferation and inhibit the activation of NLR family pyrin domain containing 3 through the circ DENND4C/miR 138-5p/FOXO3a pathway, thereby reducing pyroptosis and AKI. Circ DENND4C may be a potential therapeutic target for AKI.

ARID5B-mediated LINC01128 epigenetically activated pyroptosis and apoptosis by promoting the formation of the BTF3/STAT3 complex in ß2GPI/anti-ß2GPI-treated monocytes.

BACKGROUND: Alterations of the trimethylation of histone 3 lysine 4 (H3K4me3) mark in monocytes are implicated in the development of autoimmune diseases. Therefore, the purpose of our study was to elucidate the role of H3K4me3-mediated epigenetics in the pathogenesis of antiphospholipid syndrome (APS). METHODS: H3K4me3 Cleavage Under Targets and Tagmentation and Assay for Transposase-Accessible Chromatin were performed to determine the epigenetic profiles. Luciferase reporter assay, RNA immunoprecipitation, RNA pull-down, co-immunoprecipitation and chromatin immunoprecipitation were performed for mechanistic studies. Transmission electron microscopy and propidium iodide staining confirmed cell pyroptosis. Primary monocytes from patients with primary APS (PAPS) and healthy donors were utilised to test the levels of key molecules. A mouse model mimicked APS was constructed with beta2-glycoprotein I (ß2GPI) injection. Blood velocity was detected using murine Doppler ultrasound. RESULTS: H3K4me3 signal and open chromatin at the ARID5B promoter were increased in an in vitro model of APS. The epigenetic factor ARID5B directly activated LINC01128 transcription at its promoter. LINC01128 promoted the formation of the BTF3/STAT3 complex to enhance STAT3 phosphorylation. Activated STAT3 interacted with the NLRP3 promoter and subsequently stimulated pyroptosis and apoptosis. ARID5B or BTF3 depletion compensated for LINC01128-induced pyroptosis and apoptosis by inhibiting STAT3 phosphorylation. In mice with APS, ß2GPI exposure elevated the levels of key proteins of pyroptosis and apoptosis pathways in bone marrow-derived monocytes, reduced the blood velocity of the ascending aorta, increased the thrombus size of the carotid artery, and promoted the release of interleukin (IL)-18, IL-1ß and tissue factor. Patients with PAPS had the high-expressed ARID5B and LINC01128, especially those with triple positivity for antiphospholipid antibodies. Moreover, there was a positive correlation between ARID5B and LINC01128 expression. CONCLUSION: This study indicated that ARID5B/LINC01128 was synergistically upregulated in APS, and they aggravated disease pathogenesis by enhancing the formation of the BTF3/STAT3 complex and boosting p-STAT3-mediated pyroptosis and apoptosis, thereby providing candidate therapeutic targets for APS. HIGHLIGHTS: The H3K4me3 mark and chromatin accessibility at the ARID5B promoter are increased in vitro model mimicked APS. ARID5B-mediated LINC01128 induces pyroptosis and apoptosis via p-STAT3 by binding to BTF3. ARID5B is high- expressed in patients with primary APS and positively correlated with LINC01128 expression. OICR-9429 treatment mitigates pyroptosis and related inflammation in vivo and in vitro models mimicked APS.

Desloratadine alleviates ALS-like pathology in hSOD1G93A mice via targeting 5HTR2A on activated spinal astrocytes.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive loss of motor neurons in the spinal cord, cerebral cortex and brain stem. ALS is characterized by gradual muscle atrophy and dyskinesia. The limited knowledge on the pathology of ALS has impeded the development of therapeutics for the disease. Previous studies have shown that autophagy and astrocyte-mediated neuroinflammation are involved in the pathogenesis of ALS, while 5HTR2A participates in the early stage of astrocyte activation, and 5HTR2A antagonism may suppress astrocyte activation. In this study, we evaluated the therapeutic effects of desloratadine (DLT), a selective 5HTR2A antagonist, in human SOD1G93A (hSOD1G93A) ALS model mice, and elucidated the underlying mechanisms. HSOD1G93A mice were administered DLT (20 mg·kg-1·d-1, i.g.) from the age of 8 weeks for 10 weeks or until death. ALS onset time and lifespan were determined using rotarod and righting reflex tests, respectively. We found that astrocyte activation accompanying with serotonin receptor 2 A (5HTR2A) upregulation in the spinal cord was tightly associated with ALS-like pathology, which was effectively attenuated by DLT administration. We showed that DLT administration significantly delayed ALS symptom onset time, prolonged lifespan and ameliorated movement disorders, gastrocnemius injury and spinal motor neuronal loss in hSOD1G93A mice. Spinal cord-specific knockdown of 5HTR2A by intrathecal injection of adeno-associated virus9 (AAV9)-si-5Htr2a also ameliorated ALS pathology in hSOD1G93A mice, and occluded the therapeutic effects of DLT administration. Furthermore, we demonstrated that DLT administration promoted autophagy to reduce mutant hSOD1 levels through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocyte neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice. In summary, 5HTR2A antagonism shows promise as a therapeutic strategy for ALS, highlighting the potential of DLT in the treatment of the disease. DLT as a 5HTR2A antagonist effectively promoted autophagy to reduce mutant hSOD1 level through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocytic neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice.

Performance evaluation of a novel high-sensitivity cardiac troponin T assay: analytical and clinical perspectives.

OBJECTIVES: To evaluate the analytical characteristics of a novel high-sensitivity cardiac troponin T (hs-cTnT) test on the automatic light-initiated chemiluminescent assay (LiCA®) system, and validated its diagnostic performance for non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: Studies included an extensive analytical evaluation and established the 99th percentile upper reference limit (URL) from apparently healthy individuals, followed by a diagnostic performance validation for NSTEMI. RESULTS: Sex-specific 99th percentile URLs were 16.0 ng/L (1.7 % CV: coefficient of variation) for men (21-92 years) and 13.4 ng/L (2.0 % CV) for women (23-87 years) in serum, and 30.6 ng/L (0.9 % CV) for men (18-87 years) and 20.2 ng/L (1.4 % CV) for women (18-88 years) in heparin plasma. Detection rates in healthy individuals ranged from 98.9 to 100 %. An excellent agreement was identified between LiCA® and Elecsys® assays with a correlation coefficient of 0.993 and mean bias of -0.7 % (-1.8-0.4 %) across the full measuring range, while the correlation coefficient and overall bias were 0.967 and -1.1 % (-2.5-0.3 %) for the lower levels of cTnT (10-100 ng/L), respectively. At the specific medical decision levels (14.0 and 52.0 ng/L), assay difference was estimated to be <5.0 %. No significant difference was found between these two assays in terms of area under curve (AUC), sensitivity and specificity, negative predictive value (NPV) and positive predictive value (PPV) for the diagnosis of NSTEMI. CONCLUSIONS: LiCA® hs-cTnT is a reliable 3rd-generation (level 4) high-sensitivity assay for detecting cardiac troponin T. The assay is acceptable for practical use in the diagnosis of NSTEMI.

Intestinal dysbiosis exacerbates susceptibility to the anti-NMDA receptor encephalitis-like phenotype by changing blood brain barrier permeability and immune homeostasis.

Changes in the intestinal microbiota have been observed in patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE). However, whether and how the intestinal microbiota is involved in the pathogenesis of NMDARE susceptibility needs to be demonstrated. Here, we first showed that germ-free (GF) mice that underwent fecal microbiota transplantation (FMT) from NMDARE patients, whose fecal microbiota exhibited low short-chain fatty acid content, decreased abundance of Lachnospiraceae, and increased abundance of Verrucomicrobiota, Akkermansia, Parabacteroides, Oscillospirales, showed significant behavioral deficits. Then, these FMT mice were actively immunized with an amino terminal domain peptide from the GluN1 subunit (GluN1356-385) to mimic the pathogenic process of NMDARE. We found that FMT mice showed an increased susceptibility to an encephalitis-like phenotype characterized by more clinical symptoms, greater pentazole (PTZ)-induced susceptibility to seizures, and higher levels of T2 weighted image (T2WI) hyperintensities following immunization. Furthermore, mice with dysbiotic microbiota had impaired blood-brain barrier integrity and a proinflammatory condition. In NMDARE-microbiota recipient mice, the levels of Evan's blue (EB) dye extravasation increased, ZO-1 and claudin-5 expression decreased, and the levels of proinflammatory cytokines (IL-1, IL-6, IL-17, TNF-α and LPS) increased. Finally, significant brain inflammation, mainly in hippocampal and cortical regions, with modest neuroinflammation, immune cell infiltration, and reduced expression of NMDA receptors were observed in NMDARE microbiota recipient mice following immunization. Overall, our findings demonstrated that intestinal dysbiosis increased NMDARE susceptibility, suggesting a new target for limiting the occurrence of the severe phenotype of NMDARE.

Lactiplantibacillus plantarum L47 and inulin alleviate enterotoxigenic Escherichia coli induced ileal inflammation in piglets by upregulating the levels of α-linolenic acid and 12,13-epoxyoctadecenoic acid.

Alternatives to antibiotics for preventing bacteria-induced inflammation in early-weaned farm animals are sorely needed. Our previous study showed that Lactiplantibacillus plantarum L47 and inulin could alleviate dextran sulfate sodium (DSS)-induced colitis in mice. To explore the protective effects of L. plantarum L47 and inulin on the ileal inflammatory response in weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC), 28 weaned piglets were assigned into four groups, namely, CON group-orally given 10 mL/d phosphate buffer saline (PBS), LI47 group-orally given a mixture of 10 mL/d L. plantarum L47 and inulin, ECON group-orally given 10 mL/d PBS and challenged by ETEC, and ELI47 group-orally given 10 mL/d L. plantarum L47 and inulin mixture and challenged by ETEC. The results demonstrated that the combination of L. plantarum L47 and inulin reduced inflammatory responses and relieved the inflammatory damage caused by ETEC, including ileal morphological damage, reduced protein expression of ileal tight junction, decreased antioxidant capacity, and decreased anti-inflammatory factors. Transcriptome analysis revealed that L. plantarum L47 and inulin up-regulated the gene expression of phospholipase A2 group IIA (PLA2G2A) (P < 0.05) as well as affected alpha-linolenic acid (ALA) metabolism and linoleic acid metabolism. Moreover, L. plantarum L47 and inulin increased the levels of ALA (P < 0.05), lipoteichoic acid (LTA) (P < 0.05), and 12,13-epoxyoctadecenoic acid (12,13-EpOME) (P < 0.05) and the protein expression of Toll-like receptor 2 (TLR2) (P = 0.05) in the ileal mucosa. In conclusion, L. plantarum L47 and inulin together alleviated ETEC-induced ileal inflammation in piglets by up-regulating the levels of ALA and 12,13-EpOME via the LTA/TLR2/PLA2G2A pathway.

Efficacy and safety of Tongdutiaoshen acupuncture on insomnia in maintenance hemodialysis patients: A randomized clinical trial protocol.

Background: Patients undergoing maintenance hemodialysis (MHD) experience insomnia frequently. Poor sleep quality impairs the quality of life and adversely affects long-term outcomes. Currently, the treatment of insomnia in patients undergoing MHD is mainly based on medication, although it has severe side effects and poor compliance in patients. Therefore, developing complementary and alternative therapies with higher efficacies is important. This study explores the clinical efficacy and safety of Tongdutiaoshen acupuncture in treating insomnia in patients with MHD. Methods: This randomized controlled trial (RCT) will be performed at Beijing Luhe Hospital, affiliated with Capital Medical University in China. We will strictly adhere to the Standards for Reporting Interventions in Clinical Trials of Acupuncture (2010). A total of 110 MHD patients with insomnia will be randomly allocated in a 1:1 ratio to the drug control (DC) or Tongdutiaoshen acupuncture (TA) group. Patients in the control group will be administered estazolam tablets (1 mg/day) for four weeks, followed by a 4-week follow-up period. Based on the background therapy provided for the DC group, the TA group will be administered the interventional cohort three times a week for four weeks in a row, followed by a 4-week follow-up period. The primary endpoints will include the Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAM-A), TCM Insomnia Syndrome Score, and clinical response rate, which will be evaluated on days 0, 14, 28, and 56. Secondary endpoints will include sleep data monitoring and related laboratory indices, which will be evaluated on days 0, 28, and 56, respectively. Discussion: This study is designed based on a rigorous methodology to evaluate the efficacy and safety of Tongdutiaoshen acupuncture for insomnia in patients undergoing hemodialysis. The findings of this trial will be published in peer-reviewed journals as reliable evidence. Trial registration: Chinese Clinical Trial Registry ChiCTR2200061967. Registered on July 07, 2022.

Deep learning model for predicting the survival of patients with primary gastrointestinal lymphoma based on the SEER database and a multicentre external validation cohort.

PURPOSE: Due to the rarity of primary gastrointestinal lymphoma (PGIL), the prognostic factors and optimal management of PGIL have not been clearly defined. We aimed to establish prognostic models using a deep learning algorithm for survival prediction. METHODS: We collected 11,168 PGIL patients from the Surveillance, Epidemiology, and End Results (SEER) database to form the training and test cohorts. At the same time, we collected 82 PGIL patients from three medical centres to form the external validation cohort. We constructed a Cox proportional hazards (CoxPH) model, random survival forest (RSF) model, and neural multitask logistic regression (DeepSurv) model to predict PGIL patients' overall survival (OS). RESULTS: The 1-, 3-, 5-, and 10-year OS rates of PGIL patients in the SEER database were 77.1%, 69.4%, 63.7%, and 50.3%, respectively. The RSF model based on all variables showed that the top three most important variables for predicting OS were age, histological type, and chemotherapy. The independent risk factors for PGIL patient prognosis included sex, age, race, primary site, Ann Arbor stage, histological type, symptom, radiotherapy, and chemotherapy, according to the Lasso regression analysis. Using these factors, we built the CoxPH and DeepSurv models. The DeepSurv model's C-index values were 0.760 in the training cohort, 0.742 in the test cohort, and 0.707 in the external validation cohort, which demonstrated that the DeepSurv model performed better compared to the RSF model (0.728) and the CoxPH model (0.724). The DeepSurv model accurately predicted 1-, 3-, 5- and 10-year OS. Both calibration curves and decision curve analysis curves demonstrated the superior performance of the DeepSurv model. We developed the DeepSurv model as an online web calculator for survival prediction, which can be accessed at http://124.222.228.112:8501/ . CONCLUSIONS: This DeepSurv model with external validation is superior to previous studies in predicting short-term and long-term survival and can help us make better-individualized decisions for PGIL patients.

Regioselective Synthesis of Directly Connected BODIPY Dimers through Oxidative Coupling of α-Amino-Substituted BODIPYs.

A family of directly ß,ß-linked BODIPY dimers with amino groups at α-positions were regioselectively prepared by the oxidative coupling reaction of α-amino-substituted BODIPYs. The structure of one representative dimer was elucidated by X-ray diffraction analysis, showing its twisted orientation of two BODIPY units with a dihedral angle of 49°. Comparing with the corresponding monomers, these dimers showed red-shifted absorptions and emissions along with efficient intersystem crossing, giving ΦΔ of 43% for dimer 4b in toluene, indicating potential use as heavy-atom-free photosensitizers.

Analysis of risk factors for abdominal aortic calcification in dialysis patients and its influence on long-term recovery.

This study investigated the risk factors of abdominal aortic calcification (AAC) in patients with stage 5 chronic kidney disease (CKD) and the effects of AAC and different dialysis methods on the 3-year survival rate of patients with stage 5 CKD. A retrospective cohort study was conducted on stage 5 CKD patients who received dialysis treatment. The general data were collected, and all fasting venous blood samples were harvested before the first dialysis to detect biochemical markers. The AAC was evaluated by lateral abdominal X-ray. The patients were followed up with a cut-off date of March 31, 2022, with all-cause mortality as the endpoint event. A total of 205 patients were included. multivariable Cox regression analysis confirmed that AAC (hazard ratio (HR) = 2.173, 95% CI 1.029-4.588, p = 0.042), advanced age (HR = 1.061, 95% CI 1.031-1.093, p < 0.001), duration of dialysis (HR = 1.015, 95% CI 1.007-1.032, p < 0.001), diabetes (HR = 3.966, 95% CI 2.164-7.269, p < 0.001), and hypertension (HR = 1.897, 95% CI 1.089-3.303, p = 0.024) were independent risk factors for 3-year mortality. However, peritoneal dialysis (HR = 0.366, 95% CI 0.165-0.812, p = 0.013), high albumin (HR = 0.882, 95% CI 0.819-0.950, p = 0.001), and high hemoglobin (HR = 0.969, 95% CI 0.942-0.997, p = 0.031) were protective factors for 3-year mortality in stage 5 CKD patients. Increased age, long-term dialysis, high level of intact parathyroid hormone, diabetes, and hypertension are closely related to the occurrence of AAC in patients with stage 5 CKD. In addition, AAC is an independent risk factor for all-cause mortality in patients with stage 5 CKD.

Identification of Hypoxia-Associated Signature in Colon Cancer to Assess Tumor Immune Microenvironment and Predict Prognosis Based on 14 Hypoxia-Associated Genes.

Purpose: Colon cancer is the main malignant tumor of the digestive tract. Hypoxia is highly related to the occurrence, progression and tumor immune microenvironment (TIME) of cancer. The aim of this study was to identify a hypoxia-associated signature with high accuracy for predicting the prognosis and TIME of colon cancer. Methods: Download colon cancer data from the GEO and TCGA databases. A novel hypoxia risk model was identified to predict the prognosis of colon cancer patients. Subsequently, GSEA, TIME and mutation analysis were performed in the hypoxia high and low risk score groups. Finally, the signature gene ANKZF1 was selected for functional verification at the cellular level. Results: A novel hypoxia risk model was identified. The risk score was significantly associated with poorer overall survival in colon cancer, and could be used as an independent prognostic factor for colon cancer. GSEA analysis found that the processes related to stimulate tumor proliferation and anti-apoptosis were significantly enriched in the hypoxia high risk score group. The expression of immunosuppressive cells and most immune checkpoints in the high risk score group was significantly higher than that in the low risk score group. In vitro cell experiments showed that knockdown the expression of ANKZF1 could inhibit the proliferation, migration and invasion of colon cancer cells. Conclusion: Hypoxia plays an important role in evaluating the TIME and predicting the prognosis of colon cancer.

Direct Access to Pyrrolyltripyrrins and Calixsmaragdyrin from SNAr Reactions on α,α'-Dibromotripyrrins with Pyrroles or Indoles.

Linear π-conjugated oligopyrroles are attractive precursors for the synthesis of expanded porphyrinoids, chemosensors, and supramolecular motifs. We demonstrate a new method for the synthesis of a set of linear pyrrolyltripyrrins and dipyrrolyltripyrrins through a regioselective SNAr reaction on α,α'-dibromotripyrrins using various pyrroles or indoles. A representative calixsmaragdyrin was prepared via the 2-fold SNAr reaction between α,α'-dibromotripyrrin and dipyrromethene through a convergent [3 + 2] strategy. These oligopyrroles showed intense deep red absorptions with an interesting pH response.

The combination of endoscopic subcutaneous mastectomy and liposuction (Liu and Shang's 2-hole 7-step method) as the treatment of gynecomastia.

BACKGROUND: Most patients suffering from gynecomastia require treatment to maintain a smooth subcutaneous tissue contour, remove loose skin, and leave a suitable nipple-areolar complex with minimal scarring; hence, surgery has become the prime choice to treat gynecomastia. Based on our experience, Liu and Shang's 2-hole 7-step method works well for these patients. METHODS: From November 2021 to November 2022, a total of 101 gynecomastia patients featuring various Simon grades were included in this study. The patients' basic condition and surgical procedure were recorded in detail. A score of 1 to 5 was given for 6 main aesthetic aspects. RESULTS: With Liu and Shang's 2-hole 7-step method, the operations were successfully completed in all 101 patients. Six patients had Simon grade I, 21 grade IIA, 56 grade IIB, and 18 grade III. The average surgery time was 86.54 (range = 46-144) minutes. The average intraoperative blood loss was 22.7 (range = 10 ∼ 75) mL. The average postoperative drainage time was 2.35 (range = 1-4) days, the drainage volume was 83.35 (range = 13∼240) mL, and the drainage mainly occurred on the first postoperative day. The scores on all 6 aesthetic aspects were >4 points, which fully affirmed the aesthetic effect of this method. CONCLUSION: Liu and Shang's 2-hole 7-step method is safe and feasible for treating gynecomastia and has been fully affirmed for its efficacy and cosmetic effect. It can be the main option for minimally invasive surgery to treat gynecomastia.

Pyroptosis-triggered pathogenesis: New insights on antiphospholipid syndrome.

APS (antiphospholipid syndrome) is a systematic autoimmune disease presenting with the high levels of aPLs (antiphospholipid antibodies). These autoantibodies are involved in various clinical manifestations, mainly including arterial or venous thrombosis formation, proinflammatory response, and recurrent pregnant loss. Pyroptosis is a form of lytic programmed cell death, and it aggravates autoimmune diseases progression via activating NOD-like receptors, especially the NLRP3 inflammasome and its downstream inflammatory factors IL (interleukin)-1ß and IL-18. However, the underlying mechanisms of pyroptosis-induced APS progression remain to be elucidated. ECs (endothelial cells), monocytes, platelets, trophoblasts, and neutrophils are prominent participants in APS development. Of significance, pyroptosis of APS-related cells leads to the excessive release of proinflammatory and prothrombotic factors, which are the primary contributors to APOs (adverse pregnancy outcomes), thrombosis formation, and autoimmune dysfunction in APS. Furthermore, pyroptosis-associated medicines have made encouraging advancements in attenuating inflammation and thrombosis. Given the potential of pyroptosis in regulating APS development, this review would systematically expound the molecular mechanisms of pyroptosis, and elaborate the role of pyroptosis-mediated cellular effects in APS progression. Lastly, the prospective therapeutic approaches for APS would be proposed based on the regulation of pyroptosis.

Incidence and Clinical Features of Venous Thromboembolism in Inpatients with Mental Illness.

AIMS: We investigated the incidence and clinical features of venous thromboembolism (VTE) in inpatients with mental illnesses. METHODS: We retrospectively analyzed records of inpatients with mental illnesses and confirmed VTE at The First Hospital of Hebei Medical University between August 2018 and July 2022. We recorded demographic characteristics, psychosis-related conditions, and thrombus distribution. RESULTS: Among 12939 patients diagnosed with mental illness, 156 (1.21%) presented with VTE at the first visit or during the disease course. Crude VTE incidence varied significantly across mental illnesses, being highest in patients with organic mental disorders (5.20%), followed by emotional disorders (1.10%), and others (P < 0.001). Distal and proximal deep venous thromboses (DVT) occurred in 79.17% and 20.84% of patients, respectively. The Hamilton Depression Scale (HAMD) score was higher in patients with proximal DVT than in those with distal DVT (P < 0.001). On multivariate analysis, the HAMD score (odds ratio [OR] 1.173, confidence interval [CI] 1.100-1.251, P＜0.001) was a risk factor and the Hamilton Anxiety Scale (HAMA) (OR 0.862, CI 0.796-0.934, P＜0.001), a protective factor against DVT progression. CONCLUSION: VTE is not rare in patients with mental illnesses and is most commonly associated with organic mental disorders. Psychosis-related DVT typically shows a significantly high incidence of distal DVT. Prevention and early treatment in patients with severe depression and distal DVT can prevent DVT aggravation.