Monocytic myeloid-derived suppressor cells as an immune indicator of early diagnosis and prognosis in patients with sepsis.

BACKGROUND: Immunosuppression is a leading cause of septic death. Therefore, it is necessary to search for biomarkers that can evaluate the immune status of patients with sepsis. We assessed the diagnostic and prognostic value of low-density neutrophils (LDNs) and myeloid-derived suppressor cells (MDSCs) subsets in the peripheral blood mononuclear cells (PBMCs) of patients with sepsis. METHODS: LDNs and MDSC subsets were compared among 52 inpatients with sepsis, 33 inpatients with infection, and 32 healthy controls to investigate their potential as immune indicators of sepsis. The percentages of LDNs, monocytic MDSCs (M-MDSCs), and polymorphonuclear MDSCs (PMN-MDSCs) in PBMCs were analyzed. Sequential organ failure assessment (SOFA) scores, C-reactive protein (CRP), and procalcitonin (PCT) levels were measured concurrently. RESULTS: The percentages of LDNs and MDSC subsets were significantly increased in infection and sepsis as compared to control. MDSCs performed similarly to CRP and PCT in diagnosing infection or sepsis. LDNs and MDSC subsets positively correlated with PCT and CRP levels and showed an upward trend with the number of dysfunctional organs and SOFA score. Non-survivors had elevated M-MDSCs compared with that of patients who survived sepsis within 28 days after enrollment. CONCLUSIONS: MDSCs show potential as a diagnostic biomarker comparable to CRP and PCT, in infection and sepsis, even in distinguishing sepsis from infection. M-MDSCs show potential as a prognostic biomarker of sepsis and may be useful to predict 28-day hospital mortality in patients with sepsis.

Clinical efficacy and drug resistance of ceftazidime-avibactam in the treatment of Carbapenem-resistant gram-negative bacilli infection.

Objective: To examine the clinical efficacy, safety, and resistance of Ceftazidime-Avibactam (CAZ-AVI) in patients with Carbapenem-resistant Gram-negative bacilli (CR-GNB) infections. Methods: We retrospectively analyzed relevant data of CR-GNB infected patients receiving CAZ-AVI treatment, analyzed relevant factors affecting drug efficacy, and compared the efficacy and safety with patients receiving Polymyxin B treatment. Results: A total of 139 patients were included. Agranulocytosis, septic shock, SOFA score, and CAZ-AVI treatment course were independent risk factors affecting the prognosis of patients with CR-GNB infection treated with CAZ-AVI while prolonging the treatment course of CAZ-AVI was the only protective factor for bacterial clearance. The fundamental indicators showed no statistically significant differences between CAZ-AVI and Polymyxin B treatment groups. At the same time, the proportion of patients treated with monotherapy was significantly higher in the CAZ-AVI group than in the Polymyxin B group (37.2% vs. 8.9%, p < 0.05), the 30-day mortality rate of the CAZ-AVI treatment group (27.7% vs. 46.7%, p = 0.027) was lower than that of the Polymyxin B treatment group. The 30-day clinical cure rate (59.6% vs. 40% p = 0.030) and 14-day microbiological clearance rate (42.6% vs. 24.4%, p = 0.038) were significantly higher in the CAZ-AVI than in the Polymyxin B treatment group. Eighty nine patients were monitored for CAZ-AVI resistance, and the total resistance rate was 14.6% (13/89). The resistance rates of Carbapenem-resistant Klebsiella pneumoniae (CRKP) and Carbapenem-resistant Pseudomonas aeruginosa (CRPA) to CAZ-AVI were 13.5 and 15.4%, respectively. Conclusion: CAZ-AVI has shown high clinical efficacy and bacterial clearance in treating CR-GNB infections. Compared with Polymyxin B, CAZ-AVI significantly improved the outcome of mechanical ventilation in patients with septic shock, agranulocytosis, Intensive Care Unit (ICU) patients, bloodstream infection, and patients with SOFA score > 6, and had a lower incidence of adverse events. We monitored the emergence of CAZ-AVI resistance and should strengthen the monitoring of drug susceptibility in clinical practice and the rational selection of antibiotic regimens to delay the onset of resistance.

Nomogram for Predicting Portal Vein Thrombosis in Cirrhotic Patients: A Retrospective Cohort Study.

AIM: Portal vein thrombosis (PVT) is a common complication in cirrhotic patients and will aggravate portal hypertension, thus leading to a series of severe complications. The aim of this study was to develop a nomogram based on a simple and effective model to predict PVT in cirrhotic patients. METHODS: Clinical data of 656 cirrhotic patients with or without PVT in the First Affiliated Hospital of Soochow University and The Third Affiliated Hospital of Nantong University from January 2017 to March 2022 were retrospectively collected, and all patients were divided into training, internal and external validation cohorts. SPSS and R software were used to identify the independent risk factors and construct a predictive model. We evaluated the predictive value of the model by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses. The feasibility of the model was further validated in the internal and external cohorts. All enrolled patients were followed up to construct the survival curves and calculate the incidence of complications. RESULTS: The predictors of PVT included serum albumin, D-dimer, portal vein diameter, splenectomy, and esophageal and gastric varices. Based on the clinical and imaging findings, the final model served as a potential tool for predicting PVT in cirrhotic patients, with an AUC of 0.806 (0.766 in the internal validation cohort and 0.845 in the external validation cohort). The decision curve analysis revealed that the model had a high level of concordance between different medical centers. There was a significant difference between the PVT and non-PVT groups in survival analyses, with p values of 0.0477 and 0.0319 in the training and internal validation groups, respectively, along with p value of 0.0002 in the external validation group according to log-rank test; meanwhile, the median survival times of the PVT group were 54, 43, and 40 months, respectively. The incidence of recurrent esophageal and gastric variceal bleeding (EGVB) during the follow-up showed significant differences among the three cohorts (p = 0.009, 0.048, and 0.001 in the training, internal validation, and external validation cohorts, respectively). CONCLUSION: The nomogram based on our model provides a simple and convenient method for predicting PVT in cirrhotic patients. Cirrhotic patients with PVT had a shorter survival time and were prone to recurrent EGVB compared with those in the non-PVT group.

Leucine rich alpha-2-glycoprotein 1 (Lrg1) silencing protects against sepsis-mediated brain injury by inhibiting transforming growth factor beta1 (TGFß1)/SMAD signaling pathway.

Sepsis-associated encephalopathy (SAE) is key manifestation of sepsis which is responsible for increased morbidity and mortality. Leucine rich alpha-2-glycoprotein 1 (Lrg1) is a secreted protein implicated in a variety of diseases. We aimed to explore the effects and potential mechanism of Lrg1 on sepsis-mediated brain injury. A sepsis-induced brain damage mice model was established. Then, ELISA was utilized to detect the levels of inflammatory factors in brain tissues. Behavioral performance, spatial learning and memory of mice were evaluated by open field test and Morris water maze test. The number of neurons was tested by H&E staining. Lrg1 expression was evaluated by RT-qPCR and western blot. In vitro, mouse hippocampal neuronal cell line (HT22) was stimulated by lipopolysaccharide (LPS). After Lrg1 silencing, cell viability was determined using CCK-8 and cell apoptosis was assessed by TUNEL. The levels of inflammatory factors were detected by ELISA. Moreover, western blot was applied to analyze the expression of proteins in transforming growth factor beta1 (TGFß1)/SMAD signaling. Results revealed that mice in the model group showed obvious behavioral changes. Lrg1 was highly expressed in the brain tissues of model mice. Besides, Lrg1 knockdown suppressed the inflammation and apoptosis of LPS-induced HT22 cells. Moreover, Lrg1 silencing caused the inactivation of TGFß1/SMAD signaling. Rescue assays confirmed that TGFß1 overexpression reversed the impacts of Lrg1 deletion on the inflammation and apoptosis in LPS-induced HT22 cells. Collectively, Lrg1 silencing alleviates brain injury in SAE via inhibiting TGFß1/SMAD signaling, implying that Lrg1 might serve as a promising target for SAE treatment.

Zinc oxide nanoparticles reduce the chemoresistance of gastric cancer by inhibiting autophagy.

BACKGROUND: Gastric cancer (GC) is a common malignancy that results in a high rate of cancer-related mortality. Cisplatin (DDP)-based chemotherapy is the first-line clinical treatment for GC therapy, but chemotherapy resistance remains a severe clinical challenge. Zinc oxide nanoparticle (ZnO-NP) has been identified as a promising anti-cancer agent, but the function of ZnO-NP in GC development is still unclear. AIM: To explore the effect of ZnO-NP on chemotherapy resistance during GC progression. METHODS: ZnO-NP was synthesized, and the effect and underlying mechanisms of ZnO-NP on the malignant progression and chemotherapy resistance of GC cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, colony formation assays, transwell assays, wound healing assays, flow cytometry, and Western blot analysis in GC cells and DDP-resistant GC cells, and by tumorigenicity analyses in nude mice. RESULTS: Our data revealed that ZnO-NP was able to inhibit proliferation, migration, and invasion and induce apoptosis of GC cells. Meanwhile, ZnO-NP significantly reduced the half maximal inhibitory concentration (IC50) of DDP for the inhibition of cell proliferation of DDP-resistant SGC7901/DDP cell lines. Autophagy was increased in DDP-resistant GC cells, as demonstrated by elevated light chain 3-like protein 2 (LC3II)/LC3I and Beclin-1 expression and repressed p62 expression in SGC7901/DDP cells compared to SGC7901 cells. Mechanically, ZnO-NP inhibited autophagy in GC cells and treatment with DDP induced autophagy, which was reversed by ZnO-NP. Functionally, ZnO-NP attenuated the tumor growth of DDP-resistant GC cells in vivo. CONCLUSION: We conclude that ZnO-NP alleviates the chemoresistance of GC cells by inhibiting autophagy. Our findings present novel insights into the mechanism by which ZnO-NP regulates the chemotherapy resistance of GC. ZnO-NP may serve as a potential therapeutic candidate for GC treatment. The potential role of ZnO-NP in the clinical treatment of GC needs clarification in future investigations.

Liver function correlates with liver-to-portal vein contrast ratio during the hepatobiliary phase with Gd-EOB-DTPA-enhanced MR at 3 Tesla.

PURPOSES: To determine if liver-to-portal vein contrast ratio (LPC) correlates with liver function in patients with hepatitis B virus (HBV)-related cirrhosis on gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced MR imaging. METHODS: A total of 92 patients with normal (n = 20) or HBV-related cirrhotic livers graded by Child-Pugh class A (n = 50), B (n = 17) or C (n = 5) who underwent Gd-EOB-DTPA-enhanced 3Tesla MR imaging were retrospectively reviewed. LPC was defined as the signal intensity ratio of liver parenchyma to portal vein on hepatobiliary phase (HBP) acquired at 20 min, and it was compared between normal and cirrhotic livers. The correlation between LPC and hepatic function parameters at HBP after injection was quantitatively analyzed as well. RESULTS: LPC differed between normal and cirrhotic livers significantly (P < 0.001). LPC constantly and significantly decreased from normal to cirrhotic livers with Child-Pugh class C at HBP imaging (P < 0.001). Multiple regression analysis revealed that total bilirubin (P = 0.011), albumin (P < 0.001), and platelet count (P = 0.007) were independent predictors of LPC at HBP imaging. A receiver operating characteristic (ROC) curve analysis revealed that the optimal cutoff value for LPC to distinguish normal group from cirrhotic groups was 2.05 (AUC 0.98) with a sensitivity of 84.1% and a specificity of 100%. CONCLUSION: The level of LPC on Gd-EOB-DTPA MR imaging can efficaciously indicate the severity of liver function in patients with HBV-related cirrhosis and was correlated with liver function parameters significantly. It might be used as an alternative imaging biomarker for assessing liver function.