Uropathogenic Escherichia coli infection: innate immune disorder, bladder damage, and Tailin Fang II.

Background: Uropathogenic Escherichia coli (UPEC) activates innate immune response upon invading the urinary tract, whereas UPEC can also enter bladder epithelial cells (BECs) through interactions with fusiform vesicles on cell surfaces and subsequently escape from the vesicles into the cytoplasm to establish intracellular bacterial communities, finally evading the host immune system and leading to recurrent urinary tract infection (RUTI). Tailin Fang II (TLF-II) is a Chinese herbal formulation composed of botanicals that has been clinically proven to be effective in treating urinary tract infection (UTI). However, the underlying therapeutic mechanisms remain poorly understood. Methods: Network pharmacology analysis of TLF-II was conducted. Female Balb/C mice were transurethrally inoculated with UPEC CFT073 strain to establish the UTI mouse model. Levofloxacin was used as a positive control. Mice were randomly divided into four groups: negative control, UTI, TLF-II, and levofloxacin. Histopathological changes in bladder tissues were assessed by evaluating the bladder organ index and performing hematoxylin-eosin staining. The bacterial load in the bladder tissue and urine sample of mice was quantified. Activation of the TLR4-NF-κB pathway was investigated through immunohistochemistry and western blotting. The urinary levels of interleukin (IL)-1ß and IL-6 and urine leukocyte counts were monitored. We also determined the protein expressions of markers associated with fusiform vesicles, Rab27b and Galectin-3, and levels of the phosphate transporter protein SLC20A1. Subsequently, the co-localization of Rab27b and SLC20A1 with CFT073 was examined using confocal fluorescence microscopy. Results: Data of network pharmacology analysis suggested that TLF-II could against UTI through multiple targets and pathways associated with innate immunity and inflammation. Additionally, TLF-II significantly attenuated UPEC-induced bladder injury and reduced the bladder bacterial load. Meanwhile, TLF-II inhibited the expression of TLR4 and NF-κB on BECs and decreased the urine levels of IL-1ß and IL-6 and urine leukocyte counts. TLF-II reduced SLC20A1 and Galectin-3 expressions and increased Rab27b expression. The co-localization of SLC20A1 and Rab27b with CFT073 was significantly reduced in the TLF-II group. Conclusion: Collectively, innate immunity and bacterial escape from fusiform vesicles play important roles in UPEC-induced bladder infections. Our findings suggest that TLF-II combats UPEC-induced bladder infections by effectively mitigating bladder inflammation and preventing bacterial escape from fusiform vesicles into the cytoplasm. The findings suggest that TLF-II is a promising option for treating UTI and reducing its recurrence.

Association between a four-parameter inflammatory index and all-cause mortality in critical ill patients with non-traumatic subarachnoid hemorrhage: a retrospective analysis of the MIMIC-IV database (2012-2019).

Background: Non-traumatic subarachnoid hemorrhage (SAH), primarily due to the rupture of intracranial aneurysms, contributes significantly to the global stroke population. A novel biomarker, pan-immune-inflammation value (PIV) or called the aggregate index of systemic inflammation (AISI), linked to progression-free survival and overall survival in non-small-cell lung cancer and mortality in Coronavirus Disease 2019 (COVID-19) patients, has surfaced recently. Its role in non-traumatic SAH patients, however, remains under-researched. This study aims to determine the relationship between PIV and all-cause mortality in non-traumatic SAH patients. Methods: A retrospective analysis was conducted using data from the Medical Information Mart for Intensive Care (MIMIC-IV) database to examine the association between PIV and all-cause mortality in critically ill patients with non-traumatic SAH. PIV measurements were collected at Intensive Care Unit (ICU) admission, and several mortality measures were examined. To control for potential confounding effects, a 1:1 propensity score matching (PSM) method was applied. The optimal PIV cutoff value was identified as 1362.45 using X-tile software that is often used to calculate the optimal cut-off values in survival analysis and continuous data of medical or epidemiological research. The relationship between PIV and short- and long-term all-cause mortality was analyzed using a multivariate Cox proportional hazard regression model and Kaplan-Meier (K-M) survival curve analysis. Interaction and subgroup analyses were also carried out. Results: The study included 774 non-traumatic SAH patients. After PSM, 241 pairs of score-matched patients were generated. The Cox proportional hazard model, adjusted for potential confounders, found a high PIV (≥ 1362.45) independently associated with 90-day all-cause mortality both pre- (hazard ratio [HR]: 1.67; 95% confidence intervals (CI): 1.05-2.65; P = 0.030) and post-PSM (HR: 1.58; 95% CI: 1.14-2.67; P = 0.042). K-M survival curves revealed lower 90-day survival rates in patients with PIV ≥ 1362.45 before (31.1% vs. 16.1%%, P < 0.001) and after PSM (68.9% vs. 80.9%, P < 0.001). Similarly, elevated PIV were associated with increased risk of ICU (pre-PSM: HR: 2.10; 95% CI: 1.12-3.95; P = 0.02; post-PSM: HR: 2.33; 95% CI: 1.11-4.91; P = 0.016), in-hospital (pre-PSM: HR: 1.91; 95% CI: 1.12-3.26; P = 0.018; post-PSM: 2.06; 95% CI: 1.10-3.84; P = 0.034), 30-day (pre-PSM: HR: 1.69; 95% CI: 1.01-2.82; P = 0.045; post-PSM: 1.66; 95% CI: 1.11-2.97; P = 0.047), and 1-year (pre-PSM: HR: 1.58; 95% CI: 1.04-2.40; P = 0.032; post-PSM: 1.56; 95% CI: 1.10-2.53; P = 0.044) all-cause mortality. The K-M survival curves confirmed lower survival rates in patients with higher PIV both pre- and post PSM for ICU (pre-PSM: 18.3% vs. 8.4%, P < 0.001; post-PSM:81.7 vs. 91.3%, P < 0.001), in-hospital (pre-PSM: 25.3% vs. 12.8%, P < 0.001; post-PSM: 75.1 vs. 88.0%, P < 0.001), 30-day (pre-PSM: 24.9% vs. 11.4%, P < 0.001; post-PSM:74.7 vs. 86.3%, P < 0.001), and 1-year (pre-PSM: 36.9% vs. 20.8%, P < 0.001; P = 0.02; post-PSM: 63.1 vs. 75.1%, P < 0.001) all-cause mortality. Stratified analyses indicated that the relationship between PIV and all-cause mortality varied across different subgroups. Conclusion: In critically ill patients suffering from non-traumatic SAH, an elevated PIV upon admission correlated with a rise in all-cause mortality at various stages, including ICU, in-hospital, the 30-day, 90-day, and 1-year mortality, solidifying its position as an independent mortality risk determinant. This study represents an attempt to bridge the current knowledge gap and to provide a more nuanced understanding of the role of inflammation-based biomarkers in non-traumatic SAH. Nevertheless, to endorse the predictive value of PIV for prognosticating outcomes in non-traumatic SAH patients, additional prospective case-control studies are deemed necessary.

Intraoperative irrigation of artificial cerebrospinal fluid and temperature of irrigation fluid for chronic subdural hematoma: a systematic review and meta-analysis.

Purpose: To systematically review the different types of irrigation fluid and the different temperatures of irrigation fluid on postoperative recurrence rates in the evacuation of chronic subdural hematoma (CSDH). Methods: We conducted a comprehensive search of electronic databases, including PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), WanFang, the Chinese VIP Information (VIP), and China Biology Medicine (CBM), and reference lists of relevant studies to identify all eligible studies. Two reviewers independently screened the titles and abstracts for inclusion, and the full-text articles were assessed for eligibility based on predetermined inclusion and exclusion criteria. Data were extracted using a standardized form, and the quality of the studies was assessed using a risk of bias tool. Meta-analyses were performed using a fixed-or random-effects model, and heterogeneity was assessed using the I2 statistic. The primary endpoint was the postoperative recurrence rate. Results: After stringent screening, a total of 11 studies were identified, including six English publications, four Chinese publications, and one Japanese publication, involving a population of 29,846 patients. Our meta-analysis provides evidence that artificial cerebrospinal fluid (ACF) could decrease the post-operative recurrence rate by 47% after the evacuation of CSDH when compared to normal saline (NS) [(odds ratio) OR 0.53, 95% confidence intervals (CI): 0.31-0.90, p = 0.02, I2 = 67%]. Besides, the irrigation fluid at body temperature could decrease the postoperative recurrence rate of CSDH by 64% when compared to room temperature (OR = 0.36, 95% CI = 0.22-0.59, p < 0.0001, I2 = 0%). Conclusion: Our analysis revealed significant difference in the choice of irrigation fluid for CSDH surgery. Notably, we found that irrigation with fluid at body temperature demonstrated superiority over irrigation with fluid at room temperature, resulting in fewer instances of recurrence. This straightforward technique is both safe and widely available, providing an opportunity to optimize outcomes for patients with CSDH. Our findings suggest that the use of body-temperature NS or ACF of room temperature during operation should be considered a standard of procedure in CSDH surgery. Nevertheless, whether the different temperature of ACF could be considered a standard of procedure in CSDH surgery still need high-quality RCTs to further identify. Systematic review registration: https://www.crd.york.ac.uk/prospero/; Identifier CRD42023424344.

Association of the systemic immune-inflammation index (SII) and clinical outcomes in patients with stroke: A systematic review and meta-analysis.

Introduction: A novel systemic immune-inflammation index (SII) has been proven to be associated with outcomes in patients with cancer. Although some studies have shown that the SII is a potential and valuable tool to diagnose and predict the advise outcomes in stroke patients. Nevertheless, the findings are controversial, and their association with clinical outcomes is unclear. Consequently, we conducted a comprehensive review and meta-analysis to explore the relationship between SII and clinical outcomes in stroke patients. Methods: A search of five English databases (PubMed, Embase, Cochrane Library, Scopus, and Web of Science) and four Chinese databases (CNKI, VIP, WanFang, and CBM) was conducted. Our study strictly complied with the PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We used the NOS (Newcastle-Ottawa Scale) tool to assess the possible bias of included studies. The endpoints included poor outcome (the modified Rankin Scale [mRS] ≥ 3 points or > 3 points), mortality, the severity of stroke (according to assessment by the National Institute of Health stroke scale [NIHSS] ≥ 5 points), hemorrhagic transformation (HT) were statistically analyzed. Results: Nineteen retrospective studies met the eligibility criteria, and a total of 18609 stroke patients were included. Our study showed that high SII is significantly associated with poor outcomes (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02-1.09, P = 0.001, I2 = 93%), high mortality (OR 2.16, 95% CI 1.75-2.67, P < 0.00001, I2 = 49%), and the incidence of HT (OR 2.09, 95% CI 1.61-2.71, P < 0.00001, I2 = 42%). We also investigated the difference in SII levels in poor/good outcomes, death/survival, and minor/moderate-severe stroke groups. Our analysis demonstrated that the SII level of the poor outcome, death, and moderate-severe stroke group was much higher than that of the good outcome, survival, and minor stroke group, respectively (standard mean difference [SMD] 1.11, 95% CI 0.61-1.61, P < 0.00001 [poor/good outcome]; MD 498.22, 95% CI 333.18-663.25, P < 0.00001 [death/survival]; SMD 1.35, 95% CI 0.48-2.23, P = 0.002 [severity of stroke]). SII, on the other hand, had no significant impact on recanalization (OR 1.50, 95% CI 0.86-2.62, P = 0.16). Discussion: To the best of our knowledge, this may be the first meta-analysis to look at the link between SII and clinical outcomes in stroke patients. The inflammatory response after a stroke is useful for immunoregulatory treatment. Stroke patients with high SII should be closely monitored, since this might be a viable treatment strategy for limiting brain damage after a stroke. As a result, research into SII and the clinical outcomes of stroke patients is crucial. Our preliminary findings may represent the clinical condition and aid clinical decision-makers. Nonetheless, further research is needed to better understand the utility of SII through dynamic monitoring. To generate more robust results, large-sample and multi-center research are required. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022371996.