Early predictive value of lipocalin-type prostaglandin D synthase for 28-day mortality in cardiac arrest patients: study protocol for a prospective study.

INTRODUCTION: Public training in cardiopulmonary resuscitation and treatment in emergency and intensive care unit have made tremendous progress. However, cardiac arrest remains a major health burden worldwide, with brain damage being a significant contributor to disability and mortality. Lipocalin-type prostaglandin D synthase (L-PGDS), which is mainly localised in the central nervous system, has been previously shown to inhibit postischemia neuronal apoptosis. Therefore, we aim to observe whether serum L-PGDS can serve as a potential biomarker and explore its role in determining the severity and prognosis of patients who have achieved restoration of spontaneous circulation (ROSC). METHODS AND ANALYSIS: This is a prospective observational study. The participants (n = 60) who achieve ROSC will be distributed into two groups (non-survivor and survivor) based on 28-day survival. Healthy volunteers (n = 30) will be enrolled as controls. Each individual's relevant information will be extracted from Electronic Medical Record System in Xinhua Hospital, including demographic characteristics, clinical data, laboratory findings and so on. On days 1, 3 and 7 after ROSC, blood samples will be drawn and batch tested on the level of serum neuron-specific enolase, soluble protein 100ß, L-PGDS, procalcitonin, tumour necrosis factor-alpha and interleukin-6. The cerebral performance category score was assessed on the 28th day after ROSC. ETHICS AND DISSEMINATION: This study was performed with the approval of the Clinical Ethical Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Approval No. XHEC-C-2023-130-1). The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2300078564).

Hyperbaric oxygen therapy promotes the browning of white fat and contributes to the healing of diabetic wounds.

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.

Intestinal Piezo1 aggravates intestinal barrier dysfunction during sepsis by mediating Ca2+ influx.

INTRODUCTION: Intestinal barrier dysfunction is a pivotal factor in sepsis progression. The mechanosensitive ion channel Piezo1 is associated with barrier function; however, its role in sepsis-induced intestinal barrier dysfunction remains poorly understood. METHODS: The application of cecal ligation and puncture (CLP) modeling was performed on both mice of the wild-type (WT) variety and those with Villin-Piezo1flox/flox genetic makeup to assess the barrier function using in vivo FITC-dextran permeability measurements and immunofluorescence microscopy analysis of tight junctions (TJs) and apoptosis levels. In vitro, Caco-2 monolayers were subjected to TNF-α incubation. Moreover, to modulate Piezo1 activation, GsMTx4 was applied to inhibit Piezo1 activation. The barrier function, intracellular calcium levels, and mitochondrial function were monitored using calcium imaging and immunofluorescence techniques. RESULTS: In the intestinal tissues of CLP-induced septic mice, Piezo1 protein levels were notably elevated compared with those in normal mice. Piezo1 has been implicated in the sepsis-mediated disruption of TJs, apoptosis of intestinal epithelial cells, elevated intestinal mucosal permeability, and systemic inflammation in WT mice, whereas these effects were absent in Villin-Piezo1flox/flox CLP mice. In Caco-2 cells, TNF-α prompted calcium influx, an effect reversed by GsMTx4 treatment. Elevated calcium concentrations are correlated with increased accumulation of reactive oxygen species, diminished mitochondrial membrane potential, and TJ disruption. CONCLUSIONS: Thus, Piezo1 is a potential contributor to sepsis-induced intestinal barrier dysfunction, influencing apoptosis and TJ modification through calcium influx-mediated mitochondrial dysfunction.

Piezo1 Knockout Improves Post-Stroke Cognitive Dysfunction by Inhibiting the Interleukin-6 (IL-6)/Glutathione Peroxidase 4 (GPX4) Pathway.

Background: Cerebral infarction often results in post-stroke cognitive impairment, which impairs the quality of life and causes long-term disability. Astrocytes, the most abundant glial cells in the central nervous system, have a crucial role in cerebral ischemia and neuroinflammation. We explored the possible advantages of interleukin-6 (IL-6), a powerful pro-inflammatory cytokine produced by astrocytes, for post-stroke cognitive function. Methods: Mendelian randomization was applied to analyze the GWAS database of stroke patients, obtaining a causal relationship between IL-6 and stroke. Further validation of this relationship and its mechanisms was conducted. Using a mouse model of cerebral infarction, we demonstrated a significant increase in IL-6 expression in astrocytes surrounding the ischemic lesion. This protective effect of Piezo1 knockout was attributed to the downregulation of matrix metalloproteinases and upregulation of tight junction proteins, such as occludin and zonula occludens-1 (ZO-1). Results: Two-step Mendelian randomization revealed that IL-6 exposure is a risk factor for stroke. Moreover, we conducted behavioral assessments and observed that Piezo1 knockout mice that received intranasal administration of astrocyte-derived IL-6 showed notable improvement in cognitive function compared to control mice. This enhancement was associated with reduced neuronal cell death and suppressed astrocyte activation, preserving ZO-1. Conclusion: Our study shows that astrocyte-derived IL-6 causes cognitive decline after stroke by protecting the blood-brain barrier. This suggests that piezo1 knockout may reduce cognitive impairment after brain ischemia. Further research on the mechanisms and IL-6 delivery methods may lead to new therapies for post-stroke cognition.

Palladium-Catalyzed Carbonylative Synthesis of Polycyclic 3,4-Dihydroquinolin-2(1H)-one Scaffolds Containing Perfluoroalkyl and Carbonyl Units.

A palladium-catalyzed one-pot two-step radical mediated carbonylative cyclization of 1,7-enynes with perfluoroalkyl iodides and Mo(CO)6 has been developed for the construction of polycyclic 3,4-dihydroquinolin-2(1H)-one scaffolds. This method realizes a facile synthesis of various polycyclic 3,4-dihydroquinolin-2(1H)-one derivatives containing perfluoroalkyl and carbonyl units in high yields. Moreover, modifications of several bioactive molecules were demonstrated using this protocol.

A Novel Neutrophil-to-Lymphocyte Ratio and Sarcopenia Based TACE-Predict Model of Hepatocellular Carcinoma Patients.

Purpose: Transarterial chemoembolization (TACE) was commonly applied in hepatocellular carcinoma (HCC) patients across BCLC A-C stages with heterogeneous outcomes in real-world practice. We aimed to develop a neutrophil-to-lymphocyte ratio (NLR) and sarcopenia-based prognostic nomogram to estimate the prognosis of HCC patients after TACE treatment. Patients and Methods: Between June 2013 and December 2019, a total of 364 HCC patients who underwent TACE were included and randomly assigned to the training (n=255) and the validation cohort (n=109). Sarcopenia was diagnosed based on the third lumbar vertebra skeletal muscle mass index (L3-SMI). The multivariate Cox proportional risk model was used to generate a nomogram. Results: NLR ≥4.0, sarcopenia, alpha-fetoprotein (AFP) ≥200 ng/mL, albumin-bilirubin (ALBI) grade 2 or 3, number of lesions (≥2), and maximum size of the lesion (≥5 cm) were independent predictors for overall survival (OS) (P < 0.05). The calibration curve shows that the predicted results agree well with the observed results. The time-dependent areas under the receiver-operating characteristic curves for OS at 1, 2, and 3 years predicted by the nomogram were 0.818/0.827, 0.742/0.823, and 0.748/0.836 in both training and validation cohorts. Nomogram can divide patients into low-, medium- and high-risk groups based on predictor factors. The C-indexes of the nomogram for OS were 0.782/0.728 in the training and validation cohorts, outperforming other currently available models. Conclusion: A novel nomogram based on NLR and sarcopenia may be useful to predict the prognosis of HCC patients who underwent TACE across BCLC A-C stage patients.

Palladium-Catalyzed Cascade Carbonylative Synthesis of Perfluoroalkyl and Carbonyl-Containing 3,4-Dihydroquinolin-2(1H)-one Derivatives.

A palladium-catalyzed cascade radical cyclization and carbonylation of 1,7-enynes with perfluoroalkyl iodides and alcohols has been described. This procedure provides a facile and efficient approach for the construction of 3,4-dihydroquinolin-2(1H)-one skeletons by using benzene-1,3,5-triyl triformate (TFBen) as the CO source. This method enables the incorporation of both perfluoroalkyl and carbonyl units into the 3,4-dihydroquinolin-2(1H)-one skeletons, producing a variety of 3,4-dihydroquinolin-2(1H)-one derivatives in moderate to high yields and with excellent E/Z selectivity.

The Prognostic Value of Sarcopenia and Myosteatosis in Biliary Tract Cancer After Palliative Treatment With Radiation-Emitting Metallic Stent.

Background: Radiation-emitting metallic stent (REMS) placement is increasingly used for malignant biliary obstruction (MBO) caused by unresectable biliary tract carcinoma (UBTC) in clinical practice. The study is aimed to evaluate the prognostic value of sarcopenia, myosteatosis, and their combination on overall survival (OS) in patients treated with REMS for UBTC. Methods: Patients diagnosed with UBTC who underwent REMS placement between January 2013 and May 2021 were included consecutively in this retrospective study. Sarcopenia and myosteatosis were defined based on skeletal muscle index (SMI) and skeletal muscle attenuation (SMA), respectively, which were measured by computer tomography (CT) images on the level of the third lumbar vertebral body before REMS placement. Patients were categorized into two groups by sex-specific cutoff value for sarcopenia and myosteatosis, and OS rates were compared between the groups. Univariate and multivariate cox regression analyses were used to assess factors associated with OS. Results: Data of 135 patients included were retrospectively reviewed and analyzed. Median OS was 7.17 months in total cohort. Patients in the sarcopenia group had significant poorer OS than those in the non-sarcopenia group (median: 3.23 vs. 11.60 months, p < 0.001). OS was shorter in patients with myosteatosis than those without myosteatosis (median: 4.40 vs. 9.17 months, p < 0.001). Sarcopenia (odds ratio [OR] = 9.61; 95% CI = 5.41-17.09; p < 0.001) and myosteatosis (OR = 1.70; 95% CI = 1.13-2.57; p = 0.012) were significantly associated with OS. Combining sarcopenia and myosteatosis (CSM) showed a better predictive accuracy in OS than either one (area under curves: CSM vs. sarcopenia = 0.760 vs. 0.698, p = 0.049; CSM vs. myosteatosis = 0.760 vs. 0.671, p = 0.006). Conclusion: Sarcopenia and myosteatosis are negative predictors of survival in patients who underwent REMS placement for UBTC. CSM seemed to show a better prognostic value than either sarcopenia or myosteatosis alone. They can be used preoperatively for risk evaluation.

Clinical Strains of Pseudomonas aeruginosa Secrete LasB Elastase to Induce Hemorrhagic Diffuse Alveolar Damage in Mice.

BACKGROUND: Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are most often caused by bacterial pneumonia and characterized by severe dyspnea and high mortality. Knowledge about the lung injury effects of current clinical bacterial strains is lacking. The aim of this study was to investigate the ability of representative pathogenic bacteria isolated from patients to cause ALI/ARDS in mice and identify the major virulence factor. METHODS: Seven major bacterial species were isolated from clinical sputum and unilaterally instilled into the mouse airway. A histology study was performed to determine the lung injury effect. Virulence genes were examined by PCR. Sequence types of P. aeruginosa strains were identified by MLST. LC-MS/MS was used to analysis the bacterial exoproducts proteome. LasB was purified through a DEAE-cellulose column, and its toxicity was tested both in vitro and in vivo. RESULTS: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus agalactiae, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli were randomly separated and tested 3 times. Among them, gram-negative bacteria have much more potential to cause acute lung injury than gram-positive bacteria. However, P. aeruginosa is the only pathogen that induces diffuse alveolar damage, hemorrhage and hyaline membranes in the lungs of mice. The lung injury effect is associated with the excreted LasB elastase. Purified LasB recapitulated lung injury similar to P. aeruginosa infection in vivo. We found that this was due to the powerful degradation effect of LasB on the extracellular matrix of the lung and key proteins in the coagulation cascade without inducing obvious cellular apoptosis. We also report for the first time that LasB could induce DIC-like coagulopathy in vitro. CONCLUSION: P. aeruginosa strains are most capable of inducing ALI/ARDS in mice among major clinical pathogenic bacteria tested, and this ability is specifically attributed to their LasB production.

Association between XRCC1 polymorphisms and glioma risk among Chinese population.

The pathogenesis of glioma remains largely unknown now. It has been suggested that the X-ray cross-complementing group 1 (XRCC1) gene may influence the capacity to repair DNA damage leading to an increased gliomas susceptibility. This study aimed to evaluate the relationship between XRCC1 polymorphisms and glioma risk. Genotypes were assessed in 368 Chinese glioma patients and 346 healthy controls. XRCC1 Arg194Trp (rs1799782), Arg280His (rs25489) and Arg399Gln (rs25487) and three additional polymorphisms were directly sequenced. The frequency of Arg280His A allele was significant lower in glioma group than in healthy controls [9.6 vs 16%, OR=0.60 (0.46-0.80), P<0.001]; the frequencies of GA or AA genotypes were different in two groups (16.6 vs 22.8%, 1.3 vs 4.7%). The frequency of Arg399Gln A allele was significant higher in glioma group than in healthy controls [38.7 vs 30.1%, OR=1.29 (1.11-1.49), P=0.001]; the frequencies of GA or AA genotypes were different in two groups (45.4 vs 38.2%, 16 vs 10.9%). This study demonstrates that the rs25489 (Arg280His) and Arg399Gln (rs25487) polymorphisms in XRCC1 gene might influence the risk of developing glioma in Chinese population.

[Release of gluteal muscle contracture by radiofrequency under arthroscopy].

OBJECTIVE: To evaluate the clinical therapeutic effect of the release of gluteal muscle contracture by radiofrequency under arthroscopy. METHODS: From January 2004 to April 2005, 86 patients with gluteal muscle contracture were treated by radiofrequency release under arthroscopy.The patients were followed-up for 6-18 months(mean=12.6 months). RESULTS: Getting carriage, squatting down while keeping their knees contacting, crossing leg test, and impact on movement were served as evaluation criteria. Of the 86 patients, 79 had excellent results, 5 good, and the rest 2 were acceptable. There was no recurrence at the last follow-up, and all the patients were satisfied. CONCLUSION: For gluteal muscle contracture, radiofrequency release under arthroscopy has minimally invasion, good results and quick recovery.