The role of lipoprotein­associated phospholipase A2 in inflammatory response and macrophage infiltration in sepsis and the regulatory mechanisms.

Lipoproteinassociated phospholipase A2 (Lp-PLA2), encoded by the phospholipase A2 group VII (Pla2g7) gene, has been pertinent to inflammatory responses. This study investigates the correlation between Lp-PLA2 and inflammatory injury in septic mice and explores its regulatory mechanism. Lp-PLA2 was found to be upregulated in the serum of septic mice induced by cecal ligation and puncture and in the culture supernatant of RAW264.7 cells following lipopolysaccharide and adenosine triphosphate treatments. The contents of Lp-PLA2 were positively correlated with increased concentrations of proinflammatory cytokines in patients with sepsis. Both animal and cellular models showed increased concentrations of proinflammatory cytokines. Spi-1 proto-oncogene (Spi1), highly expressed in these models, was found to activate Pla2g7 transcription. Knockdown of Pla2g7 or Spi1 reduced the proinflammatory cytokine production, mitigated organ damage in mice, and suppressed macrophage migration in vitro. Retinoblastoma binding protein 6 (Rbbp6), poorly expressed in both models, was found to reduce Spi1 protein stability through ubiquitination modification. Rbbp6 overexpression similarly suppressed inflammatory activation of RAW264.7 cells, which was counteracted by Pla2g7 or Spi1 upregulation. In summary, this study demonstrates that the Pla2g7 loss and Spi1 upregulation participate in inflammatory responses in sepsis by elevating the Lp-PLA2 levels.

The experience of fertility concerns in patients with testicular cancer: a qualitative study.

BACKGROUND: Testicular cancer usually occurs in young adult men between the ages of 20 and 40 years, which largely coincides with the age of men's reproductive intentions. However, a serious side effect of testicular cancer therapy could reduce the fertility of patients. PURPOSE: To explore the experience of fertility concerns in patients with testicular cancer. METHODS: A phenomenological research was conducted on 12 patients with testicular cancer. Data collection was from May 2023 to August 2023, and Colaizzi analysis method was used to analyze the data. RESULTS: Four themes were found: (1) multiple worries and negative emotions, (2) fertility decision-making faces many challenges, (3) self-coping strategies for facing fertility concerns, (4) unmet supportive care needs. CONCLUSION: Medical staff should pay attention to the fertility needs of patients with testicular cancer and provide relevant interventions and support to reduce their fertility concerns.

Bibliometric analysis of research trends in the relationship between frailty and neoplasms over the past decade.

BACKGROUND: The relationship between frailty and neoplasms has attracted increasing attention from researchers in recent years. This study aims to identify current research hotspots and status in this field through bibliometric and visualization analysis. METHODS: Literature on the relationship between frailty and neoplasms, meeting the inclusion criteria, was collected from the Core Collection. Bibliometric analysis and visualization were performed using WoS, VOSviewer, and CiteSpace. RESULTS: Our study included 7410 documents on frailty and neoplasms, authored by 43,605 researchers from 9478 institutions across 115 countries, and published in 2067 journals. The USA emerged as the most productive and influential country in this field, with 3059 publications and 89,319 citations. The University of Texas MD Anderson Cancer Center and Mayo Clinic were recognized as the most productive institution and the institution with the highest citation count, respectively. The Journal of Geriatric Oncology was the leading publisher. Kirsten K Ness and James L Kirkland were identified as the most productive and most cited authors, respectively. Cluster analysis identified five key areas: body condition and nutrition, quality of life, frailty, mortality and care, and the elderly and frailty. CONCLUSION: The relationship between frailty and neoplasms remains a contentious and frequently discussed topic. Our findings indicate that research primarily focuses on cancer, the elderly, clinical trials, adverse health outcomes, frailty assessment, and nutrition.

Decarbromodiphenyl ether exposure promotes migration of triple-negative breast cancer cells through miR-221 in extracellular vesicles. / åæº´è”è‹¯é†šæš´éœ²é€šè¿‡èƒžå¤–å›Šæ³¡è£ è½½miR-221ä¿ƒè¿›ä¸‰é˜´æ€§ä¹³è ºç™Œç»†èƒžè½¬ç§».

OBJECTIVES: To investigate the effect of decarbromodiphenyl ether (BDE-209) exposure on the migration ability of triple-negative breast cancer (TNBC) cells and to explore the underlying mechanism. METHODS: Human TNBC MDA-MB-231 cells were divided into blank control group and BDE-209 exposure groups (treated with 0.02, 0.20, 2.00, 20.00 and 200.00 ng/mL BDE-209 in high glucose DMEM). Extracellular vehicles (EVs) secreted by MDA-MB-231 cells were isolated by differential ultracentrifugation. Transmission electron microscopy (SEM), nanoparticle tracking analysis (NTA) and Western blotting were performed to characterize the EVs. The effect of the EVs induced by BDE-209 exposure (EVs-BDE-209) on the migration and invasion of MDA-MB-231 cells was detected by wound-healing assay and Transwell test. qRT-PCR was used to measure the miR-221 level in EVs-BDE-209. The expression of MMP9 in MDA-MB-231 cells was determined by Western blotting. RESULTS: Compared with the blank control, BDE-209 exposure increased the tumor cell-derived EVs in dose-dependent manner. The MDA-MB-231 cells co-cultured with EVs released by 200.00 ng/mL BDE-209 exposure showed an 86% increase in cell migration rate, a 1.32-fold higher number of membrane-penetrating cells, a 2.71-fold higher expression level of miR-221, and a 1.62-fold higher expression level of MMP9 compared with the blank control group (all P<0.05). While transfection with anti-miR-221 antibody to decrease miR-221 level in EVs significantly reversed the increased invasion ability of the MDA-MB-231 cells treated with EVs-BDE-209. CONCLUSIONS: BDE-209 exposure may promote metastasis potential of MDA-MB-231 cells via EVs-BDE-209 transmitted miR-221.

Akt-mediated platelet apoptosis and its therapeutic implications in immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count which can cause fatal hemorrhage. ITP patients with antiplatelet glycoprotein (GP) Ib-IX autoantibodies appear refractory to conventional treatments, and the mechanism remains elusive. Here we show that the platelets undergo apoptosis in ITP patients with anti-GPIbα autoantibodies. Consistent with these findings, the anti-GPIbα monoclonal antibodies AN51 and SZ2 induce platelet apoptosis in vitro. We demonstrate that anti-GPIbα antibody binding activates Akt, which elicits platelet apoptosis through activation of phosphodiesterase (PDE3A) and PDE3A-mediated PKA inhibition. Genetic ablation or chemical inhibition of Akt or blocking of Akt signaling abolishes anti-GPIbα antibody-induced platelet apoptosis. We further demonstrate that the antibody-bound platelets are removed in vivo through an apoptosis-dependent manner. Phosphatidylserine (PS) exposure on apoptotic platelets results in phagocytosis of platelets by macrophages in the liver. Notably, inhibition or genetic ablation of Akt or Akt-regulated apoptotic signaling or blockage of PS exposure protects the platelets from clearance. Therefore, our findings reveal pathogenic mechanisms of ITP with anti-GPIbα autoantibodies and, more importantly, suggest therapeutic strategies for thrombocytopenia caused by autoantibodies or other pathogenic factors.

A case report of Vibrio vulnificus sepsis in a diabetic patient.

Vibrio vulnificus is a facultative anaerobic, alkalophilic, halophilic, mesophilic, Gram-negative bacterium that can cause severe wound infection, sepsis and diarrhea. This paper reported a case of 85-year-old male patient infected with Vibrio vulnificus due to being stabbed by a sea shrimp. This patient also had diabetes with a long history of alcoholism. Due to bacterial pathogenicity and the patient's underlying diseases, his condition deteriorated rapidly. Based on the rapid diagnosis of Vibrio vulnificus using the next-generation sequencing（NGS）technology and blood culture method, as well as the selection of the most effective antibiotics via drug sensitivity test, this patient underwent precise antimicrobial treatment, thorough debridement and drainage within the shortest possible time, and thus the prognosis of this patient was greatly improved. In this paper, we have systematically explored the epidemiology, clinical features, diagnosis and treatment of Vibrio vulnificus infection, thus providing a practical reference for the clinicians to quickly identify and treat possible Vibrio vulnificus infection in diabetic patients after contacting with sea water or seafood.

Successful management of exudate and odor using a pouch system in a patient with malignant facial wound: A case report.

Malignant fungating wounds are associated with heavy exudate and malodor, and can thus have a devastating impact on the physical, psychological, and functional health of patients at the end of life. Management is typically limited to the use of more absorbent dressings and frequent changing of dressings. However, this method is associated with a large amount of time needed for wound care, and does not always resolve the problem of malodor. Herein, we report the use of an inexpensive ostomy pouch to manage facial fungating wounds caused by maxillary gingival carcinoma. The pouches are adhered to the skin, and collect a large amount of malodorous exudate for days without leaking. Fewer dressing changes and the absence of malodor result in an improved quality of life for the patient and family.

[Effect of Protein Kinase A Activation on Aggregation Function of Platelets].

OBJECTIVE: To investigate the effect of protein kinase A (PKA) activation on aggregation funetion of platelets in vitro. METHODS: The peripheral blood of healthy adults were collected, and the washed platelets were gained from collected peripheral blood. The washed platelets were treated with PKA activator Forskolin, then the platelet aggregation was induced by using Ristocetin, Thrombin, Collagen and ADP respectively, the platelet aggregation level was detected by the platelet aggregator. RESULTS: Compared with the controls, 5 µmol/L forskolin significantly inhibited ADP and collagen-induced platelet aggregation (P＜0.001), and showed mild inhibiting effect on Thrombin-induced platelet aggregation (P＜0.05). 2.5-10 µmol/L forskolin significantly inhibited ADP and Collagen -induced platelet aggregation (P＜0.001); but not showed significantly inhibitory effects on Ristocetin-induced platelet aggregation (P＞0.05). CONCLUSION: PKA activation inhibits agonists-induced platelet aggregation.