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Objective To investigate the effects of hyperbaric oxygen combined with ulinastatin on choline acetyltransferase (ChAT), malondialdehyde (MDA), and myocardial function in rats with acute organophosphorus pesticide poisoning. Methods 50 specific-pathogen-free (SPF) male SD rats were randomly divided into five groups of ten each: normal group (N), model group (M), hyperbaric oxygen group (H), and ulinastatin group (U), and hyperbaric oxygen combined ulinastatin (O) group. The model of acute organophosphorus pesticide poisoning was established in the M, H, U, and O groups via cumulative subcutaneous injections on the neck back, and the N group did not set up the model. After the success of the modeling, the H group was treated with hyperbaric oxygen therapy, and the U group was intraperitoneally injected with ulinastatin at a dose of 100 000 U/kg.The O group received a combination of hyperbaric oxygen and ulinastatin treatment, whereas the N and M groups were gavaged with an equivalent volume of saline. The rats' myocardial function was assessed through cardiac echocardiography, brain tissue pathology was examined using hematoxylin and eosin (HE) staining and Nissl staining, cardiomyocyte apoptosis was evaluated by TUNEL assay, and ChAT and acetylcholine (Ach) content in rat brain tissues were determined through histochemical methods. Serum levels of MDA and superoxide dismutase (SOD) were measured using the thiobarbituric acid reactive substances (TBARS) assay. Statistical analysis was performed by SPSS 22.0. Results Compared with Group N, the left ventricular end systolic dimension (LVSD) and left ventricular end diastolic dimension (LVDD) in Group M were both enlarged, with increased interventricular septum (IVS) thickness, aggravated left ventricular strain (LVS), increased number of apoptotic cardiomyocytes, and elevated Ach and MDA levels (P<0.05). Additionally, the left ventricular ejection fraction (LVEF) decreased, while ChAT and SOD levels also decreased (P<0.05). When compared to Group M, both Groups H and U exhibited reduced LVSD and LVDD, thinner IVS, decreased LVS, and fewer apoptotic cardiomyocytes. Furthermore, Ach and MDA levels were lower (P<0.05), while LVEF, ChAT, and SOD levels were higher (P<0.05). No statistically significant difference was observed between Groups U and H (P>0.05), while Group O showed more pronounced changes compared to Group U (P<0.05). Rats in Group N exhibited normal brain tissue pathological morphology, while those in Group M suffered severe damage to brain tissue structure. Compared to Group M, significant improvements in symptoms were observed in Groups H, U, and O. Conclusions Hyperbaric oxygen combined with ulinastatin has a significant effect on acute organophosphorus pesticide poisoning rats, which can significantly increase ChAT content, decrease MDA content, and effectively improve myocardial function. [ABSTRACT FROM AUTHOR]

Objective: This comparative analysis aimed to investigate the efficacy of Sivelestat Sodium Hydrate (SSH) combined with Ulinastatin (UTI) in the treatment of sepsis with acute respiratory distress syndrome (ARDS). Methods: A control group and an observation group were formed with eighty-four cases of patients with sepsis with ARDS, with 42 cases in each group. The control group was intravenously injected with UTI based on conventional treatment, and the observation group was injected with SSH based on the control group. Both groups were treated continuously for 7 days, and the treatment outcomes and efficacy of both groups were observed. The Murray Lung Injury Score (MLIS), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) were compared. Changes in respiratory function, inflammatory factors, and oxidative stress indicators were assessed. The occurrence of adverse drug reactions was recorded. Results: The total effective rate in the observation group (95.24%) was higher than that in the control group (80.95%) (P < 0.05). The mechanical ventilation time, intensive care unit (ICU) hospitalization time, and duration of antimicrobial medication in the observation group were shorter and multiple organ dysfunction syndrome incidence was lower than those in the control group (P < 0.05). The mortality rate of patients in the observation group (35.71%) was lower than that in the control group (52.38%), but there was no statistically significant difference between the two groups (P > 0.05). MLIS, SOFA, and APACHE II scores in the observation group were lower than the control group (P < 0.05). After treatment, respiratory function, inflammation, and oxidative stress were improved in the observation group (P < 0.05). Adverse reactions were not significantly different between the two groups (P > 0.05). Conclusion: The combination of SSH plus UTI improves lung injury and pulmonary ventilation function, and reduces inflammation and oxidative stress in patients with sepsis and ARDS. [ABSTRACT FROM AUTHOR]

Introduction: In septic patients the damage of the endothelial barrier is decisive leading to circulatory septic shock with disseminated vascular coagulation, edema and multiorgan failure. Hemadsorption therapy leads to rapid resolution of clinical symptoms. We propose that the isolation of proteins adsorbed to hemadsorption devices contributes to the identification of mediators responsible for endothelial barrier dysfunction. Material and methods: Plasma materials enriched to hemadsorption filters (CytoSorb®) after therapy of patients in septic shock were fractionated and functionally characterized for their effect on cell integrity, viability, proliferation and ROS formation by human endothelial cells. Fractions were further studied for their contents of oxidized nucleic acids as well as peptides and proteins by mass spectrometry. Results: Individual fractions exhibited a strong effect on endothelial cell viability, the endothelial layer morphology, and ROS formation. Fractions with high amounts of DNA and oxidized DNA correlated with ROS formation in the target endothelium. In addition, defined proteins such as defensins (HNP-1), SAA1, CXCL7, and the peptide bikunin were linked to the strongest additive effects in endothelial damage. Conclusion: Our results indicate that hemadsorption is efficient to transiently remove strong endothelial damage mediators from the blood of patients with septic shock, which explains a rapid clinical improvement of inflammation and endothelial function. The current work indicates that a combination of stressors leads to the most detrimental effects. Oxidized ssDNA, likely derived from mitochondria, SAA1, the chemokine CXCL7 and the human neutrophil peptide alpha-defensin 1 (HNP-1) were unique for their significant negative effect on endothelial cell viability. However, the strongest damage effect occurred, when, bikunin -- cleaved off from alpha-1-microglobulin was present in high relative amounts (>65%) of protein contents in the most active fraction. Thus, a relevant combination of stressors appears to be removed by hemadsorption therapy which results in fulminant and rapid, though only transient, clinical restitution. [ABSTRACT FROM AUTHOR]

This experimental study was designed to evaluate the effect of ulinastatin, a urinary trypsin inhibitor, on postoperative cognitive dysfunction (POCD) in rats under general anesthesia with isoflurane, on the aspect of behavior, as evaluated using a Y-maze test and focusing on microglial activity. Ulinastatin (50,000 U/mL) and normal saline (1 mL) were randomly (1:1) administered intraperitoneally to the ulinastatin and control groups, respectively, before general anesthesia. Anesthesia with isoflurane 1.5 volume% was maintained for 2 h. The Y-maze test was used to evaluate cognitive function. Neuronal damage using caspase-1 expression, the degree of inflammation through cytokine detection, and microglial activation with differentiation of the phenotypic expression were evaluated. Twelve rats were enrolled in the study and evenly allocated into the two groups, with no dropouts from the study. The Y-maze test showed similar results in the two groups before general anesthesia (63 ± 12% in the control group vs. 64 ± 12% in the ulinastatin group, p = 0.81). However, a significant difference was observed between the two groups after general anesthesia (17 ± 24% in the control group vs. 60 ± 12% in the ulinastatin group, p = 0.006). The ulinastatin group showed significantly lower expression of caspase-1. Pro-inflammatory cytokine levels were significantly lower in the ulinastatin group than in the control group. The ulinastatin group had a significantly lower microglial activation (41.74 ± 10.56% in the control group vs. 4.77 ± 0.56% in the ulinastatin, p < 0.001), with a significantly lower activation of M1 phenotypes (52.19 ± 7.83% in the control group vs. 5.58 ± 0.76% in the ulinastatin group, p < 0.001). Administering ulinastatin before general anesthesia prevented neuronal damage and cognitive decline after general anesthesia, in terms of the aspect of behavior, as evaluated by the Y-maze test. The protective effect of ulinastatin was associated with the inhibition of microglial activation, especially the M1 phenotype. [ABSTRACT FROM AUTHOR]

Background: Ulinastatin, an anti-inflammatory and antioxidant trypsin inhibitor, has shown potential in mitigating acute kidney injury (AKI) and reducing serum creatinine levels after various surgeries. This retrospective study aimed to evaluate the effects of ulinastatin on AKI in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. Methods: We hypothesized that the administration of ulinastatin could prevent AKI in OPCAB. Electrical medical records were reviewed to identify OPCAB patients between January 2015 and June 2020. The utilization of ulinastatin was randomly determined and applied during this period. Acute kidney injury was defined according to the KDIGO guideline, and its incidence was compared between the ulinastatin administration group and the control group. To investigate the effect of ulinastatin on renal function, multivariate logistic regression analysis was used to calculate propensity scores for each group. Results: A total 454 OPCAB were performed, and after following inclusion and exclusion process, 100 patients were identified in the ulinastatin group and 303 patients in the control group. Using 1:2 propensity score matching, we analyzed 100 and 200 patients in the ulinastatin and control groups. The incidence of AKI was similar between the groups (2.5% for the control group, 2.0% for the ulinastatin group, p > 0.999). However, the serum creatinine value on the first post-operative day were significantly lower in the ulinastatin group compared to the control group (0.774 ± 0.179 mg/dL vs 0.823 ± 0.216 mg/dL, P = 0.040), while no significant differences were observed for the other time points (P > 0.05). The length of ICU stay day was significantly shorter in the ulinastatin group (2.91 ± 2.81 day vs 5.22 ± 7.45 day, respectively, P < 0.001). Conclusions: Ulinastatin did not have a significant effect on the incidence of AKI; it demonstrated the ability to reduce post-operative serum creatine levels at first post-operative day and shorten the length of ICU stay. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is an inflammatory bowel disease with multiple pathogeneses. Here, we aimed to study the therapeutic role of ulinastatin (UTI), an anti-inflammatory bioagent, and its associated mechanisms in treating colitis. Dextran sulfate sodium was administrated to induce colitis in mice, and a subgroup of colitis mice was treated with UTI. The gut barrier defect and inflammatory manifestations of colitis were determined via histological and molecular experiments. In addition, transcriptomics, metagenomics, and metabolomics were employed to explore the possible mechanisms underlying the effects of UTI. We found that UTI significantly alleviated the inflammatory manifestations and intestinal barrier damage in the mice with colitis. Transcriptome sequencing revealed a correlation between the UTI treatment and JAK-STAT signaling pathway. UTI up-regulated the expression of SOCS1, which subsequently inhibited the phosphorylation of JAK2 and STAT3, thus limiting the action of inflammatory mediators. In addition, 16S rRNA sequencing illustrated that UTI maintained a more stable intestinal flora, protecting the gut from dysbiosis in colitis. Moreover, metabolomics analysis demonstrated that UTI indeed facilitated the production of some bile acids and short-chain fatty acids, which supported intestinal homeostasis. Our data provide evidence that UTI is effective in treating colitis and support the potential use of UTI treatment for patients with ulcerative colitis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impacts of ulinastatin (UTI) on epithelial mesenchymal transition (EMT) and immune escape in gastric cancer (GC) cells by regulating the C-C motif chemokine ligand 2 (CCL2)-C-C motif chemokine receptor 2 (CCR2) signal axis. Methods: qRT-PCR and Western blot were applied to detect mRNA and protein expression levels of CCL2 and CCR2 in GC tissues/cells, respectively; different concentrations of UTI (0, 100, 200, 400, 800 U/ml) were applied to intervene in cells, and MTT method was applied to detect cell proliferation; AGS cells were grouped into control group, UTI group, pcDNA group and pcDNA-CCL2 group. Plate clones and Transwell cells were applied to detect cell proliferation, migration and invasion, respectively. After co-culturing AGS cells and CD8+T cells, CD8+T cells were grouped into T cell group, co-culture group, UTI group, pcDNA group and pcDNA-CCL2 group, flow cytometry was applied to detect CD8+T cell apoptosis, ELISA was applied to detect levels of IFN-γ, IL-2 and TNF-α in supernatant of CD8+T cells; Western blot was applied to detect expression of matrix metalloproteinase-2 (MMP-2), E-cadherin, Vimentin, programmed death ligand 1 (PD-L1) and CCL2-CCR2 signaling pathway proteins. Results: Expression levels of CCL2, CCR2 protein and mRNA in GC tissues/cells were increased (P<0.05) ; UTI obviously inhibited proliferation, migration, invasion and EMT of AGS cells, reduced expressions of MMP-2, Vimentin, PD-L1, CCL2 and CCR2 proteins in AGS cells, while increased expression of E-cadherin protein (P<0.05); overexpression of CCL2 was able to reverse the inhibitory effects of UTI on cell proliferation, migration, invasion and EMT; compared with T cell group, levels of IFN-γ, IL-2 and TNF-α of CD8+T cells in co-culture group were decreased, while the apoptosis rate was increased (P<0.05); compared with co culture group, levels of IFN-γ, IL-2 and TNF-α of CD8+ T cells in UTI group were increased, while the apoptosis rate was decreased (P<0.05); compared with pcDNA group, changes in the above indicators of CD8+T cells in pcDNA-CCL2 group were obviously reversed (P<0.05). Conclusion: UTI may inhibit EMT and immune escape of AGS cells by inhibiting CCL2-CCR2 signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Septic shock is a common systemic inflammatory response syndrome for critical patients in the intensive care unit. Ulinastatin is currently used for the treatment of septic shock. Our study sought to evaluate the efficacy and safety of ulinastatin in the treatment of septic shock patients. Methods: Three English databases (Embase, Medline, and Cochrane Library) and four Chinese databases (China National Knowledge Infrastructure, Wanfang data, SinoMed, and VIP) were searched for published randomized controlled trials. Stata 16.0 software was used to conduct the meta-analysis. Results: A total of 48 articles were included (Chinese article 47, 1 in English). The results show that the treatment of ulinastatin could reduce mortality (risk ratio = 0.63, 95% confidence interval (CI) (0.55, 0.72)), multiple organ dysfunction syndrome (risk ratio = 0.6, 95% CI (0.53, 0.68)), length of intensive care unit stay (mean difference (MD) = -3.92, 95% CI (-4.65, -3.18)), length of hospital stay (MD = -4.39, 95% CI (-6.63, -2.15)) and decrease Acute Physiology and Chronic Health Evaluation II score (MD = -4.55, 95% CI (-5.63, -3.47)) and Sequential Organ Failure Assessment score (MD = -2.02, 95% CI (-2.59, -1.44)) with P < 0.001. Moreover, it lowers TNF-a (standardized mean difference (SMD) = -1.78, 95% CI (-2.24, -1.32)), Interleukin-6 (SMD = -1.17, 95% CI (-1.55, -0.8)), C reactive protein (SMD = -1.49, 95% CI (-1.99, -0.99)), hypersensitive C-reactive protein (SMD = -1.9, 95% CI (-2.87, -0.94)) and procalcitonin (SMD = -0.89, 95% CI (-1.12, -0.67)) levels in the body. Conclusions: Available evidence shows that ulinastatin reduces case mortality rate, multiple organ dysfunction syndrome, length of intensive care unit stay, and length of hospital stay and decreases Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score. Moreover, it also lowers TNF-a, Interleukin-6, C reactive protein, hypersensitive C-reactive protein, and procalcitonin levels in the body. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the clinical application characteristics of ulinastatin, so as to provide reference and basis for standardizing its clinical application and updating drug instructions. METHODS: Clinical data of 3 032 inpatients with ulinastatin from Jan. 2021 to Jun. 2022 in the hospital information system of Yantai Yuhuangding Hospital was retrospectively collected, the basic data and clinical medication information were statistically analyzed. RESULTS: The majority of 3 032 patients with ulinastatin were male, accounting for 59. 96% ( 1 818 cases), with an average age of ( 60. 92 ± 14. 28) years. The top three departments ranked by case number of ulinastatin were cardiac surgery, gastroenterology and hepatobiliary surgery. A total of 742 cases (24. 47%) met the indications of drug instructions, the rest were off-label drug use, and there were 1 977 cases (65. 20%) of off-label drug use with higher level evidence-based evidence. The single dose, solvent and frequency of ulinastatin were rational, and no related adverse drug reactions occurred. The average drug utilization index of ulinastatin in the hospital was 0. 59 (<1), the overall dosage was rational. CONCLUSIONS: The off-label use of ulinastatin is common, and relevant measures should be taken to standardize the clinical application. For application with sufficient evidencebased evidence and common clinical use, it is recommended that drug manufacturers update and revise the drug inserts in a timely manner. [ABSTRACT FROM AUTHOR]

Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly‐metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase‐expressing (S18–1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI‐related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5‐8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective cohort study aimed to evaluate the clinical efficacy of ulinastatin (UTI) and azithromycin (AZM) combination therapy in treating severe pneumonia in children and its impact on inflammatory cytokines and oxidative stress.Patients and Methods: This retrospective cohort study was conducted from January 1, 2019, to January 1, 2021, involving pediatric patients diagnosed with severe mycoplasma pneumonia (SMPP). The pediatric patients were divided into two groups: those receiving UTI and AZM combination therapy (treatment group) and those receiving azithromycin alone (control group). We compared the two groups regarding clinical data, disease outcomes, inflammatory cytokines, and oxidative stress levels.Results: Baseline characteristics did not significantly differ between the two groups. UTI, in combination with AZM, significantly improved blood oxygen levels, inflammatory infection markers, and relevant clinical symptoms in patients with SMPP on the 3rd day of treatment. Additionally, it significantly reduced the levels of inflammatory cytokines TNF-a, IL-6, IL-1β, and IL-10, as well as oxidative stress markers GSH and SOD.Conclusion: Combining UTI and AZM can rapidly alleviate clinical symptoms and effectively control the progression of patients with SMPP. Therefore, this treatment approach deserves consideration for clinical promotion and utilization. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of Xuebijing combine with ulinastatin on inflammatory response and myocardial protection of neonatus with necrotizing enterocolitis (NEC). Methods: 120 neonatus with NEC who were admitted to Guangdong Women and Children Hospital from May 2019 to May 2022 were selected. According to the random number table method, they were divided into control group (intravenous infusion of physiological saline before anesthesia induction), ulinastatin group (intravenous infusion of ulinastatin injection before anesthesia induction), Xuebijing group (intravenous infusion of Xuebijing injection before anesthesia induction), and combined group (intravenous infusion of ulinastatin injection and Xuebijing injection before anesthesia induction), with 30 cases of each group. The levels of mean arterial pressure (MAP), heart rate (HR), interleukin-17 (IL-17), C-reactive protein (CRP), tumor necrosis factor -α (TNF-α), cardiac troponin (cTnI), and B-type natriuretic peptide (BNP) were compared of four groups of neonatus, and the mortality and incidence of adverse reactions of four groups were recorded. Results: There was no statistically significant difference of HR between groups before surgery(P>0.05), ulinastatin group and Xuebijing group showed that decreased compared with control group after surgery and 1 d after surgery, and combined group showed that significant decreased after surgery and 1d after surgery compared with ulinastatin group and Xuebijing group(P<0.05). There was no statistically significant difference of MAP between groups before surgery(P>0.05), ulinastatin group and Xuebijing group showed that increased compared with control group after surgery and 1 d after surgery, and combined group showed that significant increased after surgery and 1 d after surgery compared with ulinastatin group and Xuebijing group(P<0.05). The CRP, IL-17, TNF-α of ulinastatin group, Xuebijing group, and combined group after surgery and 1 d after surgery were lower than those of control group at the same time point, and combined group were lower than those of ulinastatin group and Xuebijing group at the same time point(P<0.05). The cTnI and BNP of ulinastatin group, Xuebijing group, and combined group after surgery and 1 d after surgery were lower than those of control group at the same time point, and combined group were lower than those of ulinastatin group and Xuebijing group at the same time point(P<0.05). The mortality of combined group was lower than that of control group, ulinastatin group, and Xuebijing group. There was no statistically significant difference of the incidence of adverse reactions of four groups(P>0.05). Conclusion: Perioperative use of Xuebijing combine with ulinastatin of NEC, which is beneficial for the hemodynamic stability of neonatus, can alleviate the inflammatory response of neonatus, exert myocardial protection effect, and reduce clinical mortality. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a condition of severe septicemia and septic shock caused by infection, accompanied by multiple organ dysfunction often leading to patients' admission to the intensive care unit (ICU) and death. Objective: This study aims to investigate the efficacy of urinary trypsin inhibitor in the treatment of rats with severe sepsis, and to analyze its effects on coagulation and immunity. Sixty Sprague Dawley rats were randomly divided into a model control group (MCG), an ulinastatin group (UG), and a normal control group (n = 20 each). Rats in the model CG and UG were modeled for severe sepsis through cecal ligation and puncture, and the 72 h survival of the rats in the three groups was recorded. The expression of IL-18 and TNF-α before urinary trypsin inhibitor administration and 72 h after administration was detected by an ELISA. Activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and fibrinogen (FIB) were determined using a fully automatic coagulation analyzer. CD4 + , CD8 + , and CD4 + /CD8 + levels were quantitated by flow cytometry. Results: After administration, compared with those in the MCG, rats in the UG showed higher survival rates (P < 0.05), lower IL-18 and TNF-α expression (P < 0.05), lower APTT, PT, and TT (P < 0.05), higher FIB (P < 0.05), higher CD4 + and CD4 +/CD8 + levels (P < 0.05), and significantly lower CD8 + levels (P < 0.05). Conclusion: Urinary trypsin inhibitor can increase the survival rate of rats with severe sepsis, reduce their inflammatory responses, and ameliorate coagulation disorders and immune dysfunction. [ABSTRACT FROM AUTHOR]

Background: Elderly patients are prone to postoperative cognitive dysfunction (POCD). The comparison of the effects of anesthetic adjuvant drugs on POCD in elderly patients undergoing noncardiac surgery remains controversial. Methods: The final search took place on June 10, 2023. Randomized controlled trials including ketamine, ulinastatin, dexmedetomidine, parecoxib, and midazolam on the prevention and treatment of POCD in elderly undergoing noncardiac surgery were collected. A Bayesian network meta‐analysis was performed to quantitatively combine the evidence. Results: A total of 35 randomized trials were finally included in this systematic review, and the overall risk of bias is Allocation concealment. These anesthetic adjuvant drugs did not show significant differences in preventing POCD on postoperative days 1 and 7 compared with each other, but ulinastatin may be more effective in preventing POCD than dexmedetomidine [odds ratio (OR) = 0.28, 95% confidence interval (CI) = (0.10, 0.71)] and parecoxib [OR = 0.3, 95% CI = (0.10, 0.82 on postoperative day 3. The efficiency ranking results also find that ulinastatin and ketamine might provide better effects regarding POCD prevention. Conclusions: Ketamine and ulinastatin might have better effects in preventing POCD in elderly patients undergoing noncardiac surgery. Our meta‐analysis provided evidence for the use of ulinastatin and ketamine in the prevention of POCD in elderly patients undergoing noncardiac surgery. [ABSTRACT FROM AUTHOR]

This study delves into the anti-inflammatory role of ulinastatin (UTI) in BV2 microglia cells stimulated with lipopolysaccharide (LPS), focusing on its relevance to sports and fitness players. A crucial aspect of athletic health is managing inflammation, which can impact performance and recovery. We constructed an inflammatory response model in BV2 microglia using LPS and divided the sample into four groups (n=12 each): a control group (C), an LPSinduced inflammation group (L), a UTI treatment group (U+L), and a group with A20 protein down-regulation (U+L+Si). The study evaluated IL-1β and TNF-α protein concentrations via ELISA, NF-κB/P65 and A20 protein expressions through Western blot, and microglial Iba-1 expression via immunofluorescence staining. Compared to the control, the L and U+L+Si groups showed significant increases in IL-1β, TNF-α, NF-κB P65 expression, and decreased A20 protein expression (P<0.05). The L and U+L+Si groups also exhibited higher levels of IL-1β, TNF-α, NF-κB P65, and Iba-1 compared to the U+L group (P<0.05), with reduced A20 expression. Interestingly, the U+L group displayed no significant differences in IL-1β, TNF-α, and NF-κB P65 compared to the control (P>0.05). The findings suggest that UTI significantly mitigates LPS-induced inflammation in BV2 microglia, primarily through upregulation of A20 protein. For athletes and fitness enthusiasts, these insights offer potential strategies for managing exercise-induced inflammation, enhancing recovery, and optimizing performance. [ABSTRACT FROM AUTHOR]

Purpose: To screen out potential prognostic biomarkers for HBV-related acute-on-chronic liver failure (HBV-ACLF).Patients and Methods: Peripheral blood samples of HBV-ACLF patients (n=56) and normal controls (n=15) from the Affiliated Hospital of Southwest Medical University from January 2021 to April 2022 were collected, 5 normal patients and 10 patients with ACLF were randomly selected for Data independent acquisition (DIA) mass spectrometry analysis, and the potential core proteins were screened out via bioinformatics. All samples were validated by Enzyme linked immunosorbent assays (ELISA) technology, and the survival curve was constructed based on the patient's 90-day survival time.Results: A total of 247 differentially expressed proteins (DEPs) were screened, of which 148 were upregulated and 99 were down-regulated. The DEPs were mainly enriched in high-density lipoprotein particle remodeling, coagulation, and hemostasis and participated in signaling pathways such as cholesterol metabolism, coagulation cascades, and PPAR signaling pathway. Finally, bikunin was selected for further study and validated via the ELISA, compared with the normal group, bikunin was poorly expressed in the HBV-ACLF group, the difference was statistically significant (P < 0.0001), the area under the curve (AUC) for Receiver operating characteristic (ROC) analysis was 0.917. Furthermore, compared with the non-survival group, bikunin was highly expressed in the HBV-ACLF survival group, the difference was statistically significant (P=0.0015), and the survival curve showed a positive correlation with patient survival (P=0.0063).Conclusion: The level of plasma bikunin in HBV-ACLF is down-regulated, which is positively correlated with the survival of the patients with HBV-ACLF, and is expected to become a new prognostic biomarker. [ABSTRACT FROM AUTHOR]

To investigate the effect of sevoflurane combined with ulinastatin on cell proliferation and migration of human lung adenocarcinoma. Human lung adenocarcinoma cells H1975 were cultured in vitro, and treated with different concentrations of sevoflurane, ulinastatin and sevoflurane+ulinastatin, the cells were divided into control group, sevoflurane, ulinastatin and sevoflurane+ulinastatin group by cell counting kit 8; H1975 cell cycle by flow cytometry; the number of H1975 cells was measured by Transwell; protein immunoblot (Western blot). Compared with the control group, different concentrations of sevoflurane and ulinastatin treatment significantly inhibited the proliferation of H1975 cells in a dose-dependent manner. Sevoflurane combined with ulinastatin had a synergistic effect on cell proliferation inhibition in H1975 cells. Compared with the control group, the inhibition of cell proliferation and the proportion of cells in growth 0/growth 1 phase were significantly increased in the sevoflurane and ulinastatin groups, the proportion of cells in S phase, the number of cell migration, proliferation proteins cyclin D1, cyclin-dependent kinase 4, migration protein matrix metalloproteinase-2 and matrix metalloproteinase-9 were significantly decreased (p<0.05); compared with the sevoflurane group and the ulinastatin group, the inhibition of cell proliferation and the percentage of cells in growth 0/growth 1 group, the proportion of cells in S phase, cell migration number, proliferation proteins cyclin D1, cyclin-dependent kinase 4, migration proteins matrix metalloproteinase-2 and matrix metalloproteinase-9 were significantly decreased (p<0.05). Sevoflurane combined with ulinastatin can synergistically downregulate proliferation and migration protein expression and then inhibit the proliferation and migration of lung adenocarcinoma cells H1975, which may be a potential treatment for lung adenocarcinoma in clinical practice. [ABSTRACT FROM AUTHOR]

This experimental study was designed to evaluate the effect of ulinastatin, a urinary trypsin inhibitor, on postoperative cognitive dysfunction (POCD) in rats under general anesthesia with isoflurane, on the aspect of behavior, as evaluated using a Y-maze test and focusing on microglial activity. Ulinastatin (50,000 U/mL) and normal saline (1 mL) were randomly (1:1) administered intraperitoneally to the ulinastatin and control groups, respectively, before general anesthesia. Anesthesia with isoflurane 1.5 volume% was maintained for 2 h. The Y-maze test was used to evaluate cognitive function. Neuronal damage using caspase-1 expression, the degree of inflammation through cytokine detection, and microglial activation with differentiation of the phenotypic expression were evaluated. Twelve rats were enrolled in the study and evenly allocated into the two groups, with no dropouts from the study. The Y-maze test showed similar results in the two groups before general anesthesia (63 ± 12% in the control group vs. 64 ± 12% in the ulinastatin group, p = 0.81). However, a significant difference was observed between the two groups after general anesthesia (17 ± 24% in the control group vs. 60 ± 12% in the ulinastatin group, p = 0.006). The ulinastatin group showed significantly lower expression of caspase-1. Pro-inflammatory cytokine levels were significantly lower in the ulinastatin group than in the control group. The ulinastatin group had a significantly lower microglial activation (41.74 ± 10.56% in the control group vs. 4.77 ± 0.56% in the ulinastatin, p < 0.001), with a significantly lower activation of M1 phenotypes (52.19 ± 7.83% in the control group vs. 5.58 ± 0.76% in the ulinastatin group, p < 0.001). Administering ulinastatin before general anesthesia prevented neuronal damage and cognitive decline after general anesthesia, in terms of the aspect of behavior, as evaluated by the Y-maze test. The protective effect of ulinastatin was associated with the inhibition of microglial activation, especially the M1 phenotype.

Ulinastatin, a broad spectrum of serine protease inhibitor, has been found to alleviate neuropathic pain (NPP). However, its mechanism is not completely clear. Here, a sciatic nerve ligation rat model and BV2 microglial cells were used to investigate the effect of Ulinastatin on the activation of microglia and P2Y12 receptors in vivo and in vitro. Levels of P2Y12 receptor and NF-κB (P65) expression in the dorsal horn of the lumbar enlargement region of the spinal cord and BV2 cells were assessed by immunohistochemistry and double-label immunofluorescence assays. Levels of IL-1β and TNF-α in cell culture medium and cerebrospinal fluid (CSF) were examined by ELISA. The results showed that Ulinastatin reduced the release of inflammatory IL-1β and TNF-α by inhibiting the activation of spinal microglia. Ulinastatin down-regulated P2Y12 receptor and NF-κB (P65) expression in the spinal microglia of the chronic constrictive injury model. The results indicated that Ulinastatin may attenuate the activation of spinal microglia after peripheral nerve injury by inhibiting the activation of P2Y12 receptor signal pathway in microglia. NF-kB may play a key role in the mechanism of Ulinastatin. [ABSTRACT FROM AUTHOR]

Background: Severe Acute pancreatitis (SAP) is a pancreatic inflammatory disease that has a high mortality. Ulinastatin, a urinary trypsin inhibitor that can be used in SAP. However, there are limited studies comparing Ulinastatin and octreotide in SAP. This study was done to study the efficacy of Ulinastatin in SAP patients in comparison with Octreotide. Methods: A prospective observational study was conducted among 49 SAP patients in the surgical in-patient unit at Goa medical college from January to March 2021. Patients either received Ulinastatin or Octreotide as part of their routine care and the institutional protocol. Various clinical outcomes, blood, and urine amylase levels were compared between two treatment groups. For statistical analysis SPSS version 20 was used. Results: The mean age of the patients was 40.31 ± 9.45 years. The cause of pancreatitis was alcohol usage in 42(85.71%), gallstones in 4 (8.16%), and pseudocyst in 3 (6.12%). Among the study population, 29 (59.18%) patients received Ulinastatin, and 20 (40.82%) received Octreotide. The mean blood amylase was 1452.11 ± 716.54 units per liter before treatment and 945.15 ± 397.03 after treatment. The mean urine amylase was 2432.37 ± 765.22 units per liter before treatment and 1064.7 ± 495.12 after treatment. The differences in the blood and urine amylase levels before and after treatment was statistically significant (P-value <0.001). Conclusion: This study has shown that Ulinastatin has better outcome than Octreotide in treatment of patients with severe acute pancreatitis. [ABSTRACT FROM AUTHOR]

Prostate cancer is a male malignant tumor disease with high incidence and mortality. This study was designed to explore the effects of ulinastatin (UTI) on the malignant progression of prostate cancer and its relevant mechanism of action. Human prostate cancer cell line PC‐3 was applied to investigate the anticancer activity of UTI. PC‐3 cells were treated with increasing concentrations (400, 800, and 1600 U/ml) of UTI. Cell proliferation, migration, invasion, and apoptosis were determined by cell counting kit‐8 (CCK‐8), colony formation, wound‐healing, Transwell assay, and flow cytometry analysis, respectively. The expression level of corresponding proteins was detected by western blot. In addition, PC‐3 cells were pretreated with RhoA agonist CN03 (1 μg/ml) or NLRP3 agonist nigericin (10 μM) before UTI treatment, and the cellular behaviors above were detected again. It was demonstrated that UTI significantly suppressed cell proliferation, migration, and invasion but promoted apoptosis in PC‐3 cells in a concentration‐dependent manner. Meanwhile, UTI could block RhoA/ROCK/NLRP3 inflammasome pathway in PC‐3 cells, and the activation of RhoA or NLRP3 inflammasome partly weakened the impacts of UTI on cell proliferation, migration, and apoptosis in PC‐3 cells, respectively. In summary, our study demonstrated the antitumor activity of UTI against prostate cancer by regulating RhoA/NLRP3 inflammasome pathway, providing a promising candidate drug for the therapeutic treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Bikunin is a small chondroitin sulfate proteoglycan (PG) with Ser-protease inhibitory activity that plays pleiotropic roles in health and disease. It is involved in several physiological processes including stabilization of the extracellular matrix (ECM) of connective tissues and key reproductive events. Bikunin is also implicated in both acute and chronic inflammatory conditions and represents a non-invasive circulating and/or urinary (as Urinary Trypsin Inhibitor or UTI) biomarker. It exerts inhibitory effects on urokinase-type plasminogen activator (uPA) and its receptor (uPAR) mediating tumor invasiveness by a down-regulation of uPA mRNA expression, thus representing an anti-metastatic agent. However, only limited data on its potential as a diagnostic and/or prognostic marker of cancer have been reported so far. Recent technological advances in mass spectrometry-based proteomics have provided researchers with a huge amount of information allowing for large-scale surveys of the cancer proteome. To address such issues, we analyzed bikunin expression data across several types of tumors, by using UALCAN proteogenomic analysis portal. In this article we critically review the roles of bikunin in human pathobiology, with a special focus on its inhibitory effects and mechanisms in cancer aggressiveness as well as its significance as cancer circulating biomarker. [ABSTRACT FROM AUTHOR]

Cerebral ischemia results in loss of cerebral blood flow, which contributes to neuronal damage, neurocognitive impairment, as well as learning and memory difficulties. Although reperfusion is necessary to restore the blood supply to the brain, it also leads to several detrimental effects on the brain. The purpose of this study was to assess the effects of ulinastatin (UTI) on preventing focal cerebral ischemia/reperfusion‐induced injury (FCIRI). First, a rat model of FCIRI was established and treated with UTI. The effects of UTI on FCIRI in rats were evaluated using Morris water maze assay, triphenyl tetrazolium chloride staining, TUNEL, western blot assay, and enzyme‐linked immunosorbent assay analysis. UTI was found to improve the learning memory ability, reduce infarction area, inhibit apoptosis and decrease inflammation in FCIRI rats. Messenger RNA microarray analysis of hippocampal tissues revealed that suppressor of cytokine signalling‐1 (SOCS1) was the downstream target of UTI in FCIRI. SOCS1 depletion impaired the protective effect of UTI on FCIRI in rats. SOCS1 blocked the activation of the JAK2/STAT3 pathway. JAK2 inhibitor caused the JAK2/STAT3 pathway deficit, hence reversing the effect of sh‐SOCS1 on FCIRI in rats. Taken together, our results demonstrate that UTI alleviated FCIRI in rats, which was, to some extent, related to SOCS1‐mediated JAK2/STAT3 pathway. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effect and mechanism of ulinastatin (UTI) on development of lungs in fetal rabbits with intrauterine growth retardation (IUGR). Methods: Twenty pregnant rabbits were equally divided into normal, IUGR, UTI, and LY groups. The normal group was only injected with saline and marked with tattoo ink. IUGR models were established by injecting N-nitro-L-arginine methyl ester in the rabbits of IUGR, UTI, and LY groups. The three groups were injected with saline, UTI, or UTIþ LY294002 (PI3K inhibitor) respectively, and then marked with tattoo ink. After cesarean section, neonatal weights, and levels of dipalmitoyl phosphatidylcholine (DPPC), nitric oxide (NO), P-Akt, P-eNOS, and pulmonary surfactant-associated protein A (SP-A) were determined in tissues of the lungs. Radial alveoli count (RAC), pulmonary interstitial ratio, and ultrastructural changes in type II alveolar epithelial cells (AEC II) were also determined through light and electron microscopy. Results: Compared with control, the IUGR group showed significantly decreased weight, RAC, lamellar bodies in AEC II, and levels of P-Akt, P-eNOS, DPPC, NO, and SP-A, and increased pulmonary interstitial ratio (p < .05). The UTI treatment did not affect the weight; however, all other parameters were opposite to those observed in the IUGR group (p < .05). Furthermore, these UTI-mediated changes were inhibited by LY294002. Conclusions: Intraperitoneal UTI injection can promote the development of lungs and increase pulmonary surfactant production in IUGR fetal rabbits, potentially by activating PI3K/Akt/eNOS/ NO signaling. [ABSTRACT FROM AUTHOR]

Ketamine (KET) is widely used for induction and maintenance of anesthesia, and long-term use is required for treatment of depression patients. Repeated use of KET is associated with mood and memory disorders. Ulinastatin (UTI), a urinary trypsin inhibitor, has been widely undertaken as an anti-inflammatory drug and proved to have neuroprotective effects. The aim of this work was to determine whether prophylactic use of UTI could attenuate KET-induced cognitive impairment. It was found that repetitive KET anesthesia cause cognitive and emotional disorders in adolescent mice in WMZ and OFT test, while UTI pretreatment reversed the poor performance compared to the AK group, and the platform finding time and center crossing time were obviously short in the CK+UTI group (P < 0.05). Our ELISA experiment results discovered that UTI pretreatment reduced the expression levels of IL-1β and IL-6 induced by CK anesthesia compared to AK (P < 0.05). In addition, UTI pretreatment protected the cognitive function by restraining the expression levels of Tau protein, Tau phospho-396 protein, and Aβ protein in the CK group compared to the AK group in Western blotting (P < 0.05). The results suggested that UTI could act as a new strategy to prevent the neurotoxicity of KET, revealing a significant neuroprotective effect of UTI. [ABSTRACT FROM AUTHOR]

Objective: To explore and analyze the curative effect of different doses of ulinastatin combined with micro injection pump meropenem on patients with severe pneumonia and the influence of angiopoietin-2. Methods: From January 2019 to February 2022, 78 patients with severe pneumonia who were diagnosed and treated in our hospital were selected as research objects, and they were divided into a research group and a control group with 39 cases in each group. Both groups were given micro-bolus injection of meropenem. The study group and the control group were treated with high-dose and low-dose ulinastatin, respectively, for 7 consecutive days, and the curative effect and serum angiopoietin-2 expression changes were observed. Results: The ICU hospitalization time, antipyretic time, inflammation absorption time and sputum color change time of the study group were shorter than those of the control group (P<0.05). The total effective rate of the treatment group was higher than that of the control group (P<0.05). The levels of serum interleukin-6 (IL-6) and interleukin-17 (IL-17) in the two groups after treatment were significantly lower than those before treatment (P<0.05). The -17 content was also significantly lower than that in the control group (P<0.05). The serum Angiopoietin-2 content of the two groups after treatment was lower than that before treatment, and the serum Angiopoietin-2 content of the study group was lower than that of the control group after treatment (P<0.05). Conclusion: The application of high-dose ulinastatin combined with micro-injection pump meropenem in patients with severe pneumonia can inhibit the expression of serum angiopoietin-2, as well as the expression of serum IL-6 and IL-17, thereby improving the therapeutic effect. The effect is to promote the improvement of the patient's clinical symptoms, which is conducive to the recovery of the patient. [ABSTRACT FROM AUTHOR]

Ulinastatin, a common adjuvant drug in the clinical treatment of acute circulatory failure, has a good effect on various inflammatory diseases. In this study, we aim to explore the clinical efficacy of ulinastatin combined with meglumine adenosine cyclophosphate in patients with acute myocardial infarction (AMI) and its effect on cardiac function and endothelial function of patients. 100 AMI patients treated in our hospital (February 2020-October 2020) were randomly chosen and divided into group J and group Q, with 50 cases in each group. Group Q was treated with meglumine adenosine cyclophosphate only, while group J was treated with ulinastatin combined with meglumine adenosine cyclophosphate to compare the treatment efficiency, cardiac structure indexes, cardiac systolic function, blood lipid levels, vascular endothelial function, QLI (quality of life) scores, BI indexes, and FMA (motor function) scores between the two groups. The treatment efficiency, QLI score, BI index, and FMA score in group J were notably higher compared with group Q (P < 0.05). The cardiac structure indexes, cardiac systolic function, blood lipid level, and vascular endothelial function in group J were notably better compared with group Q (P < 0.05). Ulinastatin combined with meglumine adenosine cyclophosphate can obviously enhance the therapeutic effect of AMI patients and improve the endothelial function and cardiac function of patients, which is very promising in this medical area. [ABSTRACT FROM AUTHOR]

Recombinant protein engineering design affects therapeutic properties including protein efficacy, safety, and immunogenicity. Importantly, glycosylation modulates glycoprotein therapeutic pharmacokinetics, pharmacodynamics, and effector functions. Furthermore, the development of fusion proteins requires in-depth characterization of the protein integrity and its glycosylation to evaluate their critical quality attributes. Fc-fusion proteins can be modified by complex glycosylation on the active peptide, the fragment crystallizable (Fc) domain, and the linker peptides. Moreover, the type of glycosylation and the glycan distribution at a given glycosite depend on the host cell line and the expression system conditions that significantly impact safety and efficacy. Because of the inherent heterogeneity of glycosylation, it is necessary to assign glycan structural detail for glycoprotein quality control. Using conventional reversed-phase LC–MS methods, the different glycoforms at a given glycosite elute over a narrow retention time window, and glycopeptide ionization is suppressed by co-eluting non-modified peptides. To overcome this drawback, we used nanoHILIC-MS to characterize the complex glycosylation of UTI-Fc, a fusion protein that greatly increases the half-life of ulinastatin. By this methodology, we identified and characterized ulinastatin glycopeptides at the Fc domain and linker peptide. The results described herein demonstrate the advantages of nanoHILIC-MS to elucidate glycan features on glycotherapeutics that fail to be detected using traditional reversed-phase glycoproteomics. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is an important complication of rhabdomyolysis (RM), but there is lack of effective treatments. Ulinastatin (UTI) is a broad-spectrum serine protease inhibitor isolated and purified from human urine with strong anti-inflammatory and cytoprotective actions. The aim of this research was to investigate the effect and potential mechanism of UTI on RM-induced AKI (RM-AKI). We established RM-induced AKI model and myoglobin (Mb)-stimulated NRK-52E cell model. In vivo, twenty-four rats were randomly divided into three groups (n = 8): control, RM-AKI, and RM-AKI + UTI. In vitro, the NRK-52E cells were divided into six groups according to the different treatment method. Mb-stimulated NRK-52E cells were treated with UTI or si-TLR4 transfection to characterize the mechanisms of UTI in RM-AKI. Indicators of the kidney injury, cell viability, cell cycle, oxidative stress, inflammation, apoptosis, and TLR4/NF-κB signaling pathway were assessed. In vivo and in vitro, UTI significantly decreased the expression of TLR4 and p65. In vivo, UTI significantly improved renal function and reduced inflammatory reaction and kidney injury. In vitro, UTI protected NRK-52E cells from Mb stimulation by suppressing cell cytotoxicity, cell cycle inhibition, overproduction of ROS, inflammation, and apoptosis. Additionally, UTI played a protective role by downregulating the TLR4 expression. The results indicate that UTI alleviates RM-AKI by suppressing the inflammatory response and apoptosis via inhibiting TLR4/NF-κB signaling pathway. Our study provides a new mechanism for the protective effect of UTI on RM-AKI. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Effects of Ulinastatin on Postoperative Renal Function in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass: A Prospective Cohort Study with 10-Year Follow-Up." The correction states that the 6th author, Jia Shi, was incorrectly listed as the corresponding author due to a publisher error. The correct corresponding author is the last author, Hong Lv. The online version of the article has been updated to reflect this correction. The article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License. [Extracted from the article]

Background: Data on interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) are conflicting. The aim of this study was to assimilate data from RCTs. Methods: MEDLINE and Embase databases were searched systematically for RCTs evaluating interventions to reduce all grades of POPF or clinically relevant (CR) POPF after PD. Meta-analysis was undertaken for interventions investigated in multiple studies. A post hoc analysis of negative RCTs assessed whether these had appropriate statistical power. Results: Among 22 interventions (7512 patients, 55 studies), 12 were assessed by multiple studies, and subjected to meta-analysis. Of these, external pancreatic duct drainage was the only intervention associated with reduced rates of both CR-POPF (odds ratio (OR) 0.40, 95 per cent c.i. 0.20 to 0.80) and all-POPF (OR 0.42, 0.25 to 0.70). Ulinastatin was associated with reduced rates of CR-POPF (OR 0.24, 0.06 to 0.93). Invagination (versus duct-to-mucosa) pancreatojejunostomy was associated with reduced rates of all-POPF (OR 0.60, 0.40 to 0.90). Most negative RCTs were found to be underpowered, with post hoc power calculations indicating that interventions would need to reduce the POPF rate to 1 per cent or less in order to achieve 80 per cent power in 16 of 34 (all-POPF) and 19 of 25 (CR-POPF) studies respectively. Conclusion: This meta-analysis supports a role for several interventions to reduce POPF after PD. RCTs in this field were often relatively small and underpowered, especially those evaluating CR-POPF. [ABSTRACT FROM AUTHOR]

Objective(s): Previous studies have shown that ulinastatin (UTI) alleviates pulmonary edema in acute lung injury (ALI) caused by lipopolysaccharide (LPS), although the mechanism behind this action is uncertain. This research aimed to identify the fundamental mechanism by which UTI alleviates pulmonary edema. Materials and Methods: We established a model of acute lung injury (ALI) in rats by using LPS as the inciting agent.The control, LPS, and LPS+UTI groups were each comprised of a specific number of randomly selected Wistar rats. We evaluated lung injury and determined pulmonary edema. The concentrations of TNF-α, IL-1β and IL-6 in BALF and the expression levels of α1Na, k-ATPase, β1Na, K-AtPase, α-ENaC, β-ENaC, γ-ENaC, Zonula occludens (ZO)-1, Occludin, Caludin-5, PI3K, Akt, TLR4, MyD88 and NF-κBwere identified in lung tissues. Results: The presence of UTI was associated with a reduction in lung pathological alterations, lung injury scores, the lung W/D ratio, and MPO activity, in addition to the improved gas exchange (P<0.01). Furthermore, UTI alleviated EB leakage and stimulated AFC (P<0.01). Importantly, UTI increased the expression of ZO-1, Occludin, Caludin-5, α1Na, K-ATPase, β1Na, K-AtPase, α-ENaC, β-ENaC, and γ-ENaC (P<0.01). Furthermore, UTI inhibited the inflammatory response, enhanced the expression of PI3K and Akt and hindered TLR4, MyD88, and NF-κB expression (P<0.01) in lung tissues. Conclusion: Our results demonstrated that UTI attenuated pulmonary edema by reducing pulmonary permeability and promoting AFC through inhibiting the inflammatory response, and the mechanism is related to promoting PI3K/Akt signaling pathways and suppressing TLR4/MyD88/NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a pneumonic response characterized by neutrophil infiltration. Macrophage efferocytosis is the process whereby macrophages remove apoptotic cells, and is required for ALI inflammation to subside. The glycoprotein ulinastatin (UTI) has an anti-inflammatory effect during the acute stages of ALI, but its effect on efferocytosis and the subinflammatory stage of ALI is unclear. Extracellular signal-regulated kinase 5 (ERK5) is a key protein in efferocytosis, and we thus hypothesized that it may be activated by UTI to regulate efferocytosis and the resolution of pneumonia. To test this hypothesis, here we monitored phagocytosis of macrophages through in vivo and in vitro experiments. Pulmonary edema, neutrophil infiltration, protein exudation, and inflammatory factor regression were observed on days 1, 3, 5, and 7 in vivo. RAW264.7 cells were pretreated with different concentrations of UTI and ERK5 inhibitors, and the expression of tyrosine-protein kinase Mer (Mer) protein on macrophage membrane was detected. UTI increased the phagocytosis of apoptotic neutrophils by macrophages in vitro and in vivo, and promoted the resolution of pneumonia. The protein expression of ERK5 and Mer increased with UTI concentration, while the expression of Mer was down-regulated by ERK5 inhibitors. Therefore, our results suggest that UTI enhances efferocytosis and reduces lung inflammation and injury through the ERK5/Mer signaling pathway, which may be one of the targets of UTI in the treatment of lung injury. [ABSTRACT FROM AUTHOR]

Background: The safety assessment of ulinastatin can guide clinical practice. The present study aimed to investigate the real-world safety of ulinastatin in China. Methods: This multicenter study retrospectively analyzed the post-marketing surveillance data of consecutive patients treated with ulinastatin between August 2014 and June 2017 in the general wards and the intensive care units (ICU) of nine hospitals in China. Adverse drug reactions/adverse drug events (ADRs/ADEs) were collected and evaluated in a post-marketing database. Results: A total of 11,252 consecutive patients were included in the study: 7009 ICU patients and 4243 general ward patients. Eleven patients with ADRs/ADEs were observed, including nine ICU patients and two general ward patients. The clinical manifestations were liver dysfunction (n = 5 ICU cases, n = 1 general case), thrombocytopenia (n = 2 ICU cases, n = 1 general case), leukopenia (n = 1 ICU case), and rash (n = 1 ICU case). During the study period, the drug ADR/ADE rate of ulinastatin injection was 0.98‰ (11/11,252 × 1000‰). Among the 11,252 valid patients, only 327 received ulinastatin in accordance with the drug specifications. After excluding unreasonable drug use, the calculated ADR rate was 3.06‰ (1/327 × 1000‰) (95% confidence interval: 0.0‰-17.1‰). In ICU and general ward patients, the use of other drugs combined with ulinastatin was associated with the occurrence of ADRs/ADEs (100% with ADRs/ADEs vs. 0% in controls, P < 0.001). Conclusions: The incidence of ADRs/ADEs of ulinastatin is < 5‰. The ADRs/ADEs involved limited organs, mainly the skin, gastrointestinal tract, and blood. In most cases, the ADRs/ADEs gradually alleviated or recovered after drug withdrawal. The inappropriate/off-label use of ulinastatin should be the focus of surveillance. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical effect of linezolid in combination with ulinastatin on respiratory function and serum inflammatory factors in elderly patients with severe pneumonia. Methods: Ninety-eight (98) elderly patients with severe pneumonia in Nuclear Industry 416 Hospital (January 2019 - January 2020) were equally randomized into group M and group N. Group M patients received linezolid alone, while those in group N received linezolid in combination with ulinastatin. Indices related to respiratory function such as maximal mid-expiratory flow (MMF), peak expiratory flow (PEF), maximal expiratory pressure (PEmax), maximal inspiratory pressure (Pimax), as well as serum inflammatory factors such as C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were determined. Results: Total treatment effectiveness, pulmonary function indexes and arterial blood gas indices were higher in group N, while serum inflammatory factors and CPIS and APACHE II scores were lower, when compared with group M (p < 0.05). The incidence of adverse reactions in both groups was comparable (p > 0.05). Conclusion: Combined use of linezolid and ulinastatin produces marked therapeutic effect in elderly patients with severe pneumonia. It effectively lowers serum inflammatory factor levels, elevates arterial blood gas indices and improves pulmonary function. However, further clinical trials are required prior to its introduction in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of low molecular weight heparins (LMWHs) and ulinastatin on soluble myeloid cells and intestinal mucosal function (IMF) in patients with severe pancreatitis. Methods: A total of 107 patients with severe pancreatitis were divided into two groups: control group (CG, n = 53) and study group (SG, n = 54). The CG was treated with LMWH while SG was similarly treated but in addition received ulinastatin simultaneously. The following parameters were evaluated in the two groups: treatment effects, IMF, time for various indicators to normalize, vascular endothelial function, complication symptoms, T lymphoid subgroup indicators, inflammatory factors, antiinflammatory factors, soluble B7-H2, and soluble myeloid cell receptor-1 level changes. Results: After treatment, SG showed lower levels of L/M value, DAO and D-lactic acid than in CG (p < 0.05). Gastrointestinal function, leukocytes, amylase, and body temperature in SG had a shorter time to return to normal than in CG (p < 0.05). The levels of IL-10 in SG were higher than in CG, while sB7-H2, TNF-α, sTREM-1 and IL-1 levels were lower than those in the CG (p < 0.05). After treatment, NO levels in SG were higher, but TXB2, vWF and ET levels were lower than in CG (p < 0.05). In addition, CD4+, CD4+/CD8+ indicators were higher and CD8+ lower in SG than in CG (p < 0.05). Conclusion: Ulinastatin + LMWHs improves IMF in patients suffering from severe pancreatitis, shortens the time for various indicators to normalize, and reduces incidence of complications. However, further clinical trials are required to ascertain this therapeutic strategy for the management of severe pancreatitis. [ABSTRACT FROM AUTHOR]

Introduction: Increased permeability of the renal capillaries is a common consequence of sepsis-associated acute kidney injury. Vascular endothelial (VE)-cadherin is a strictly endothelial-specific adhesion molecule that can control the permeability of the blood vessel wall. Additionally, autophagy plays an important role in maintaining cell stability. Ulinastatin, a urinary trypsin inhibitor, attenuates the systemic inflammatory response and visceral vasopermeability. However, it is uncertain whether ulinastatin can improve renal microcirculation by acting on the endothelial adhesion junction. Methods: We observed the effect of ulinastatin in a septic rat model using contrast-enhanced ultrasonography (CEUS) to evaluate the perfusion of the renal cortex and medulla. Male adult Sprague Dawley rats were subjected to cecal ligation and puncture and divided into the sham, sepsis, and ulinastatin groups. Ulinastatin (50,000 U/kg) was injected into the tail vein immediately after the operation. The CEUS was performed to evaluate the renal microcirculation perfusion at 3, 6, 12, and 24 h after the operation. Histological staining was used to evaluate kidney injury scores. Western blot was used to quantify the expression of VE-cadherin, LC3II, and inflammatory factors (interleukin-1β, interleukin-6, and tumor necrosis factor-α) in kidney tissue, and enzyme-linked immunosorbent assay detected serum inflammatory factors and kidney function and early kidney injury biomarker levels. Results: Compared with the sham group, ulinastatin reduced the inflammatory response, inhibited autophagy, maintained the expression of VE-cadherin, and meliorated cortical and medullary perfusion. Conclusion: Ulinastatin effectively protects the adhesion junction and helps ameliorate the perfusion of kidney capillaries during sepsis by the inhibition of autophagy and the expression of inflammatory factors. [ABSTRACT FROM AUTHOR]

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Background: Acute type A aortic dissection (ATAAD) is a heterogeneous systemic inflammatory response syndrome. Identification of distinct inflammatory phenotypes may allow more precise therapy and improved care. We aim to investigate whether distinct inflammatory subphenotypes exist in ATAAD patients and respond differently to pharmacotherapies. Methods: Retrospective analysis of data sets was conducted from the Additive Anti-inflammatory Actions for Aortopathy & Arteriopathy (5A) III study. Inflammatory subphenotypes were derived among 2008 ATAAD patients who received surgical repair at 11 Chinese hospitals (2016– 2020) using latent class analysis applied to 14 laboratory signatures within 6 hours of hospital admission. Outcomes included operative mortality (Society of Thoracic Surgeons definition), derived subphenotype frequency, and the potential consequences of phenotype frequency distributions on the treatment effects. Results: The median (interquartile range) age of patients was 54 (45– 62) years, and 1423 (70.9%) were male. A two-class (two subphenotype) model was an improvement over a one-class model (P<·>P=0· 007) than did those with the hypoinflammatory subphenotype. Furthermore, the interaction between ulinastatin treatment and subphenotype is not significant for operative mortality (P=0.15) but for ventilator time (P=0· 04). Conclusion: Two subphenotypes of ATAAD were identified in the 5A cohort that correlated with clinical outcomes, with significant interaction effect between anti-inflammatory treatment and subphenotypes for ventilator time, suggesting these phenotypes may help in understanding heterogeneity of treatment effects. Trial Registration: Clinical Trials. Gov: number NCT04918108. [ABSTRACT FROM AUTHOR]

Sepsis is a leading cause of morbidity and mortality in the intensive care unit, which is caused by unregulated inflammatory response leading to organ injuries. Ulinastatin (UTI), an immunomodulatory agent, is widely used in clinical practice and is associated with improved outcomes in sepsis. But its underlying mechanisms are largely unknown. Our study integrated bulk and single cell RNA-seq data to systematically explore the potential mechanisms of the effects of UTI in sepsis. After adjusting for potential confounders in the negative binomial regression model, there were more genes being downregulated than being upregulated in the UTI group. These down-regulated genes were enriched in the neutrophil involved immunity such as neutrophil activation and degranulation, indicating the immunomodulatory effects of UTI is mediated via regulation of neutrophil activity. By deconvoluting the bulk RNA-seq samples to obtain fractions of cell types, the Myeloid-derived suppressor cells (MDSC) were significantly expanded in the UTI treated samples. Further cell-cell communication analysis revealed some signaling pathways such as ANEEXIN, GRN and RESISTIN that might be involved in the immunomodulatory effects of UTI. The study provides a comprehensive reference map of transcriptional states of sepsis treated with UTI, as well as a general framework for studying UTI-related mechanisms. [ABSTRACT FROM AUTHOR]

Background. Myocardial ischemia-reperfusion injury (MIRI) is a very common adverse reaction after cardiac valve replacement (CVR) under cardiopulmonary bypass, which seriously affects the rehabilitation and prognosis of patients. Objective. The prevention and treatment of MIRI are a hotspot of modern medical research, and this study is aimed at providing reliable reference and guidance for future clinical prevention and treatment of MIRI by analyzing the effects of ulinastatin (UL) on cardiac function and MIRI of patients after CVR. Methods. A total of 104 patients undergoing CVR under cardiopulmonary bypass in our hospital were selected as research participants. Among them, 52 patients treated with UL were assigned to the observation group, and the rest 52 patients given the same amount of normal saline were assigned to the control group. The cardiopulmonary bypass status, postoperative status, cardiac function, inflammatory response, oxidative stress response, and hemodynamics were observed and compared between the two groups. In addition, clinical efficacy and safety and patient prognosis were compared. Results. Through experimental analysis, we found that UL had no significant effect on the clinical efficacy, safety, and prognosis of patients after surgery (P > 0.05) but had obvious protective effects on cardiopulmonary bypass status, cardiac function, inflammation, oxidative stress, and hemodynamics (P < 0.05). Conclusion. UL can effectively prevent the occurrence of MIRI after CVR under cardiopulmonary bypass, which is worthy of clinical application. [ABSTRACT FROM AUTHOR]

Background:Find the use of ulinastatin as a treatment option which is safe as well as potentially useful for the patients suffering from COVID-19.Material and Methods:In COVID-19 many authors have proposed Ulinastatin historically as an anti-inflammatory and anti-oxidation agent which has also been clinically utilized for the treatment of circulatory shock, acute respiratory distress syndrome (ARDS) and severe sepsis.Results:Clinical and laboratory data in critically ill ICU patient with COVID-19 in this case series, received treatment with Ulinastatin 1 lakh units i.v Q12h on day 1 of admission, was added and continued for 3 to 5 days and had a remarkable clinical improvement.Conclusion:In this case series the use of Ulinastatin was found to be safe & potentially helpful for patients affected with moderate to severe COVID illness with fast improvement in clinical condition. [ABSTRACT FROM AUTHOR]

Kidney disease is a worldwide public health problem, affecting between 8% and 16% of the global population. Chronic kidney disease is a silent disease and its detection is often late, making the treatment difficult. Actual diagnosis is based on dosage of canonical renal biomarkers like serum creatinine and observation of proteinuria/albuminuria which would be relatively insensitive to disease progression which usually is detected too late for any efficient therapeutic intervention. Besides, cardiovascular alterations and uremic toxins accumulation play a negative role in biological functions and lead to the main causes of death in a kidney damage situation. In this way, the development of options for real-time detection of kidney injuries is an urgent need. Considering the emerging Fourier-Transform Infrared spectroscopy (FTIR) as biophotonic resource for the biomedical sciences, we aimed to identify spectral signatures related to biomarkers of chronic kidney disease in human blood serum using micro-FTIR option. We investigated samples from 17 healthy individuals and 33 chronic kidney disease patients. Serum samples were analyzed by micro-reflectance FTIR and compared to routine blood and urinary exams (urinary creatinine, glucose, glycated hemoglobin, creatinine, urea, total proteins, albumin) outcomes. We notice that separator gel in VACUETTE® container tubes is a relevant source of spectral interference which decreased the accuracy of discrimination from 85% to 65%. Acquiring diluted gel signal as background would improve the discrimination performance in spite of some gel bands still present in samples data. In this case our results indicated that vibrations associated with galactose-4-sulfate, CH 2 bending of the methylene chains, C = C in lipids and fatty acids, C = O stretching of lipids, C = N stretching, CH bending vibration from the phenyl rings, N-H bending vibration coupled to C-N stretching, β -sheet of Amide II, and phenyl ring were modulated in blood serum samples of chronic kidney disease patients compared to healthy individuals. Urinary trypsin inhibitors, fatty acids, phenolic derivatives, tryptophan, and plasminogen were the biomolecules related to these assignments. In conclusion, micro-FTIR is a viable option for fast diagnosis of chronic kidney disease being also a powerful tool for monitoring the disease. We propose a method enabling large batches analysis, being eligible technology for clinical laboratories in healthcare facilities. However, for direct clinical applications ATR-FTIR would be the option of choice. [ABSTRACT FROM AUTHOR]

To investigate impact of ulinastatin (UTI) on sigma-1 receptor (σ1R) and binding immunoglobulin protein (BiP) after cerebral ischemia/reperfusion injury. The middle cerebral artery occlusion (MCAO) model was used to induce cerebral ischemia/reperfusion injury. Eighty male Sprague Dawley rats were randomly divided into 6 groups: control, MCAO, MCAO+50,000 U/kg UTI, MCAO+100,000 U/kg UTI, MCAO+200,000 U/kg UTI, MCAO+300,000 U/kg UTI. At 24 and 48 hours after MCAO, infarct volume, neurological dysfunction, and grip strength test were measured, and level of σ1R and BiP proteins was further detected using Western blot. Molecular docking assays were carried out to verify interaction between σ1R, BiP, and UTI. The serum concentration of BiP and the binding assay between σ1R, BiP, and UTI were determined using enzyme-linked immunosorbent assay. UTI increased the modified neurological severity score and upregulated σ1R and BiP expression in the cerebral cortex after MCAO. The grip strength of forelimbs increased significantly in the MCAO+200,000 U/kg UTI and MCAO+300,000 U/kg UTI groups compared with the MCAO group, while BiP serum levels remained unchanged. The molecular docking assay indicated putative binding between σ1R, BiP, and UTI. The binding assay also revealed that both σ1R and BiP could be combined with UTI. UTI displays a neuroprotective effect via upregulation of σ1R and BiP during ischemia/reperfusion injury, suggesting that UTI modulates σ1R and BiP and their interaction may provide a novel insight into potential therapeutic mechanisms for stroke. [ABSTRACT FROM AUTHOR]

Purpose: To determine the efficacy and safety of a combination of ulinastatin and meglumine cyclic adenosine monophosphate (cAMP) in the treatment of acute myocardial infarction (AMI), and its effect on serum levels of hypersensitive-c-reactive protein (hs-CRP), cardiac troponin I (cTnI), creatine kinase (CK). Methods: A total of 90 AMI patients admitted to The Second Affiliated Hospital of Qiqihar Medical College, Qiqihar City, Heilongjiang Province, China from January 2019 to January 2020 were selected and randomized (in a 1:1 ration) into control group and study group. Patients in the two groups received meglumine cAMP, while those in the study group were, in addition, treated with ulinastatin. The two groups were compared with regard to clinical efficacy, cardiac function indices, serum biochemical indices, incidence of drug-related side effects, duration and number of episodes of angina pectoris, and levels of neuroendocrine hormones. Results: The study group exhibited remarkably higher treatment effectiveness and cardiac function indices compared to the control group (p < 0.05). However, lower levels of serum biochemical indices, lower total incidence of drug toxicity, smaller number and shorter duration of angina pectoris, and lower levels of panel reactive antibodies (PRA) were observed in the study when compared to control group (p < 0.001). Conclusion: Treatment of AMI patients with the combination of ulinastatin and meglumine cAMP significantly reduces the clinical symptoms of the patients, with remarkable efficacy and high safety. Furthermore, it down-regulates serum levels of hs-CRP, cTnI and CK. Thus, the combination treatment seems superior to the conventional therapy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the application of gabexate mesilate in inpatients from this hospital, so as to evaluate its rationality. METHODS: Medical records of 328 inpatients using gabexate mesilate in this hospital during 2019-2020 were acquired, patients' general information, hospitalization information and medication information were collected, the medication rationality was evaluated according to domestic and overseas guidelines and literature; totally 286 non-surgical patients diagnosed with acute pancreatitis were screened out, effects of different dosage regimens of gabexate mesylate on the treatment outcomes were preliminarily discussed. RESULTS: Among the 328 inpatients using gabexate mesilate, 22 cases ( 6. 71 % ) were off-label and over-indication medication, all of them were surgical patients; 94 cases ( 28. 66%) were inappropriate solvents, 93 cases used 0. 9% sodium chloride injection as the solvent and 1 case used 10% dextrose injection as the solvent; 7 cases(2. 13%) were over-fast infusion speed, which was >2. 5 mg/( kg·h) ; 161 cases ( 49. 09%) were combined application with ulinastatin. The combined application of ulinastatin and the different dosage regimens (≤5 d and > 6 d) did not have significant effects on laboratory indicators, remission time of abdominal pain and length of hospital stay ( P>O. 05). CONCLUSIONS: The clinical application of gabexate mesylate is still inadequate, and the clinic should pay close attention to promote its rational application. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is one of the most common diseases in patients treated in intensive care units. This study was intended to explore the underlying mechanism by which ulinastatin (UTI) influenced the inflammation and apoptosis of renal tubular epithelial cells, HK-2. The effects of UTI on the cell viability of HK-2 cells were first measured by MTT and lactate dehydrogenase (LDH) detection kit. The apoptosis and inflammation of HK-2 cells were then determined by TUNEL, western blot, ELISA, and RT-qPCR. Then, the proteins in the Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) and nuclear factor erythroid 2–related factor 2 (Nrf2)/Heme oxygenase 1 (HO-1) signaling pathways were measured by western blot for confirming the relationship between UTI and these pathways. Finally, Nrf-2 inhibitor ML385 and TLR4 activator CCL-34 were respectively used on LPS-induced HK-2 cells exposed to UTI for the conduction of gain-of-function and loss-of-function assays. UTI treatment boosted the cell viability of HK-2 cells damaged by LPS. Furthermore, UTI exposure cut down the apoptosis rate and inhibited the expression inflammatory factors of HK-2 cells induced by LPS. UTI treatment decreased the expression of proteins in the TLR4/NF-κB pathway, increased the HO-1 expression, and prompted the translocation of Nrf2 from the cytoplasm to the nucleus. The alleviated effects of UTI on inflammation and apoptosis LPS-induced HK-2 cells were abolished by ML385 and TLR4, respectively. UTI attenuates LPS-induced inflammation and inhibits endoplasmic reticulum stress–induced apoptosis in renal tubular epithelial cells by regulating TLR4/NF-κB and Nrf2/HO-1 pathways. [ABSTRACT FROM AUTHOR]

Objectives: Pyroptosis, a special kind of cell death, is generally believed to aggravate the inflammatory response. It has been found that the acinar cell pyroptosis exits in the course of pancreatitis. Ulinastatin has the function of inhibiting the release of inflammatory mediators, thereby reducing the inflammatory reaction, which suggests that ulinastatin has potential inhibitory effect on pyroptosis. The aim of this study is to investigate the effect of ulinastatin on caspase-1-dependent acinar cell pyroptosis in acute pancreatitis. Methods: Acute pancreatitis model was established by intraperitoneal injection of L-arginine. Rats in ulinastatin group were injected with ulinastatin intravenously after successful modeling. The pancreatic tissues of rats were subjected to pathological examination and detection of cleaved-caspase-1, GSDMD-N, IL-1β, and IL-18. Serum samples were also collected for measurement of IL-1β, IL-18, amylase, and lipase. Results: Slight pathological damage of pancreas was observed in the pancreatitis and the ulinastatin group. Compared with the blank control group (p <.05), the protein levels of cleaved-caspase-1, GSDMD-N, IL-1β, and IL-18 were significantly increased in pancreatitis group but decreased in ulinastatin group (p <.05). The positive reaction of caspase-1 in pancreatitis group was significantly higher than that in the blank control group (p <.05). After administration of ulinastatin, the positive reaction of caspase-1 was significantly lower than that in pancreatitis group (p <.05). As for the levels of serum IL-1β and IL-18, they were significantly higher in pancreatitis group than those in the blank control group (p <.05). Administration of ulinastatin significantly decreased the serum levels of IL-1β and IL-18 (p <.05). And the serum amylase and lipase levels elevated in pancreatitis group, while significantly inhibited by ulinastatin (p <.05). Conclusions: The results showed that the onset of acute pancreatitis was accompanied by obvious acinar cell pyroptosis. Ulinastatin could inhibit caspase-1-dependent acinar cell pyroptosis in acute pancreatitis. [ABSTRACT FROM AUTHOR]