Serum interα-trypsin inhibitor heavy chain H4 may be an anti-inflammatory marker reflecting disease risk, activity and treatment outcome of ankylosing spondylitis.

Interα-trypsin inhibitor heavy chain H4 (ITIH4) modulates inflammation and immunity, which take part in the pathogenesis of ankylosing spondylitis (AS). The current research intended to discover the clinical value of serum ITIH4 quantification for AS management. Serum ITIH4 among 80 AS patients before current treatment initiation (baseline) at weeks (W) 4, 8 and 12 after treatment was detected by ELISA. Serum ITIH4 from 20 disease controls (DCs) and 20 healthy controls (HCs) was detected. ITIH4 expression was lower in AS patients than in DCs (p = 0.002) and HCs (p < 0.001). Among AS patients, ITIH4 was negatively associated with C-reactive protein (CRP) (r = -0.311, p = 0.005), bath AS disease activity index (BASDAI) (r = -0.223, p = 0.047), total pack pain (r = -0.273, p = 0.014) and AS disease activity score (ASDAS) (CRP) (r = -0.265, p = 0.018). Meanwhile, ITIH4 was negatively related to tumor necrosis factor (TNF)-α (r = -0.364, p = 0.001), interleukin (IL)-1ß (r = -0.251, p = 0.025), IL-6 (r = -0.292, p = 0.009) and IL-17A (r = -0.254, p = 0.023). After treatment, the assessment of the spondylitis arthritis international society 40 response rate was 28.7% at W4, 46.3% at W8 and 55.0% at W12; ITIH4 showed an increasing trend from baseline to W12 (p < 0.001). Furthermore, ITIH4 at W8 (p = 0.020) and W12 (p = 0.035), but not at baseline or W4 (both p > 0.05), was enhanced in response patients vs. nonresponse patients. Additionally, ITIH4 at W12 was increased in AS patients receiving TNF inhibitors vs. those receiving nonsteroidal anti-inflammatory drugs (NSAIDs) (p = 0.024). Serum ITIH4 increases after treatment, and its augmentation is correlated with lower disease activity, decreased inflammation and enhanced treatment response in AS patients.

Targeting protein-protein interaction for immunomodulation: A sunflower trypsin inhibitor analog peptidomimetic suppresses RA progression in CIA model.

Protein-protein interactions (PPI) of co-stimulatory molecules CD2-CD58 are important in the early stage of an immune response, and increased expression of these co-stimulatory molecules is observed in the synovial region of joints in rheumatoid arthritis (RA) patients. A CD2 epitope region that binds to CD58 was grafted on to sunflower trypsin inhibitor (SFTI) template structure to inhibit CD2-CD58 PPI. The peptide was incorporated with an organic moiety dibenzofuran (DBF) in its structure. The designed peptidomimetic was studied for its ability to inhibit CD2-CD58 interactions in vitro, and its thermal and enzymatic stability was evaluated. Stability studies indicated that the grafted peptidomimetic was stable against trypsin cleavage. In vivo studies using the collagen-induced arthritis (CIA) model in mice indicated that the peptidomimetic was able to slow down the progress of arthritis, an autoimmune disease in the mice model. These studies suggest that with the grafting of organic functional groups in the stable peptide template SFTI stabilizes the peptide structure, and these peptides can be used as a template to design stable peptides for therapeutic purposes.

Influence of nimodipine combined with ulinastatin on neurological function and inflammatory reaction in patients with cerebral vasospasm after subarachnoid hemorrhage.

OBJECTIVE: This study aimed to discuss the influence of nimodipine+ulinastatin on the neurological function and inflammatory reaction in patients with cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). METHODS: Overall, 90 patients with CVS after SAH who were admitted to our hospital were enrolled in this study and randomly divided into research and control groups (n = 45 for both groups). On the basis of conventional therapy, patients in the control group were injected with ulinastatin and those in the research group were injected with ulinastatin+nimodipine through an intravenous drip for 7 days with the others the same as those of the control group. RESULTS: Blood flow velocity in all cerebral arteries was lower in the research group than in the control group after treatment (P < 0.05). Calcitonin gene-related peptide and nitric oxide levels were higher in the research group than in the control group after treatment (P < 0.05). Endothelin levels were lower in the research group than in the control group (P < 0.05). The total effective rate was higher in the research group than in the control group (P < 0.05). Glasgow Coma Scale scores were higher in the research group than in the control group (P < 0.05). CONCLUSION: The drug combination of nimodipine and ulinastatin improved blood flow and neurological function in patients with CVS after SAH and enhanced the therapeutic efficacy; the underlying mechanism may be associated with the regulation of vascular endothelial dilatation function and the inhibition of relevant inflammatory factors' expression.

Traditional Chinese medicine for septic patients undergoing ulinastatin therapy: A meta-analysis.

PURPOSE: This study aimed to assess the efficacy of traditional Chinese medicine (TCM) in septic patients treated with ulinastatin. METHODS: PubMed, EmBase, and the Cochrane library were searched up to January 2021 to identify randomized controlled trials. The weight mean difference (WMD) and relative risk (RR) with 95% confidence intervals were used with the random-effects model. RESULTS: Twenty-three randomized controlled trials with 1903 septic patients were included. TCM significantly reduced the APACHE II score (WMD: -5.18; P < .001), interleukin-6 (WMD: -63.00; P < .001), tumor necrosis factor-α (WMD: -8.86; P < .001), c-reactive protein (WMD: -9.47; P < .001), mechanical ventilation duration (WMD: -3.98; P < .001), intensive care unit stay (WMD: -4.18; P < .001), procalcitonin (WMD: -0.53; P < .001), lipopolysaccharide (WMD: -9.69; P < .001), B-type natriuretic peptide (WMD: -159.87; P < .001), creatine kinase isoenzyme MB (WMD: -45.67; P < .001), cardiac troponin I (WMD: -0.66; P < .001), and all-cause mortality risk (RR: 0.55; P < .001). CONCLUSIONS: TCM lowers inflammation levels and reduces the risk of all-cause mortality for septic patients.

Systematic review and meta-analysis of the efficacy of trypsin inhibitors in patients with severe pancreatitis.

BACKGROUND: This study aimed to explore the efficacy of trypsin inhibitors in the treatment of severe pancreatitis (SP) by meta-analysis. METHODS: The Boolean logic retrieval method was adopted to recruit the relevant literature. Chinese and English databases were respectively searched using a combination of the following search terms: "trypsin inhibitor", "acute pancreatitis", and "severe pancreatitis". The trypsin-treated SP group was set as the experimental group, and the blank control was set as the control group. Meta-analysis was performed using RevMan 5.3 software provided by the Cochrane system. RESULTS: A total of 12 references were included. The meta-analysis suggested that the heterogeneity test results of pancreatic infection incidence were Chi2 =0.51, degrees of freedom (df) =7, I2=0%<50%, and P=1.00>0.01, with risk ratio (RR): 0.80, 95% confidence interval (CI): (0.64, 1.01), Z=1.88, and P=0.06. The heterogeneity test results of extra-pancreatic infection incidence were Chi2 =0.20, df =5, I2=0%<50%, and P=1.00>0.01, with RR: 0.81, 95% CI: (0.62, 1.05), Z=1.60, and P=0.11. The heterogeneity test results of the length of hospital stay were Tau2 =65.69, Chi2 =75.05, df =6, I2=92%>50%, and P<0.0001. The length of hospital stay of the experimental group was shorter than that of the control group, with mean difference (MD): -23.31 and the 95% CI: (-29.60, -17.02), and the difference was statistically significant (Z=7.26, P<0.0001). The heterogeneity test results of the inflammatory factor tumor necrosis factor-α (TNF-α) level were Chi2 =67.28, df =3, I2=96%>50%, and P<0.0001. The level of TNF-α in the experimental group was lower than that in the control group, with MD: -11.69, 95% CI: (-12.51, -10.87), and the difference was statistically significant (Z=27.88, P<0.0001). The heterogeneity test results of the mortality rate were Chi2 =2.52, df =5, I2=0%<50%, and P=0.77>0.01. The mortality rate of the experimental group was lower than that of the control group, with RR: 0.27 and 95% CI: (0.19, 0.40), and the difference was notable (Z=6.75, P<0.0001). DISCUSSION: The meta-analysis performed in this study confirmed that trypsin inhibitors can inhibit the release of inflammatory factors and reduce mortality rate of SP patients.

Protective Effects of Reduced Glutathione and Ulinastatin on Xeno-transplanted Human Ovarian Tissue Against Ischemia and Reperfusion Injury.

Recently, transplantation of cryopreserved ovarian tissue is the method for fertility preservation for oncologic and nononcologic reasons. The main challenge of ovarian cryopreservation followed by transplantation is that ischemia reperfusion injury (IRI) induced the loss of follicles. The aim of this study was to evaluate the effects of glutathione (GSH), ulinastatin (UTI) or both (GSH+UTI) on preventing ischemia reperfusion-induced follicles depletion in ovarian grafts.Ovarian fragments were collected from 20 women aged 29±6 years. Frozen-thawed human ovarian tissue was xenografted into SCID mice, at the same time GSH, UTI and GSH+UTI was administrated respectively. The ovarian grafts were collected at the 1st, 3rd, 7th, 14th, 28th, 56th, and 85th day after xenotransplantation. Follicle survival rate was measured by H&E staining and Live/Dead staining. Angiogenic activity and macrophage recruitment was evidenced by immunohistochemical staining. The oxidative stress and inflammatory cytokines in human ovarian xenografts were measured by real-time PCR. The results indicated that after the treatments of GSH, UTI and GSH+UTI in the hosts, follicular survival in ovarian grafts were improved. The level of VEGF, CD31, and antioxidant enzymes superoxide dismutase 1 and superoxide dismutase 2 in ovarian grafts were increased. Accumulation of macrophages, level of IL6 and TNF-α, as well as malondialdehyde was decreased in ovarian grafts from treated groups. In conclusion, administration of GSH, UTI and GSH+UTI decreased the depletion of follicles in human grafts post-transplantation by inhibiting IRI-induced antiangiogenesis, oxidative stress and inflammation.

Nafamostat Mesylate is Not Effective in Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with complications such as post-ERCP pancreatitis (PEP). Protease inhibitors, including nafamostat mesylate (NM), have been evaluated for prophylaxis against PEP. AIM: We describe the first multicenter randomized controlled trial assessing the prophylactic efficacy of NM against PEP. METHODS: In this multicenter prospective study, we aimed to enroll 800 patients aged ≥ 20 years with a planned ERCP between December 2012 and March 2019. The primary outcome was the incidence and severity of PEP in patients who did not receive NM (non-NM) versus those who did (NM; 20 mg). Secondary outcomes included the incidence of PEP by NM initiation (pre- and post-ERCP), risk factors for PEP, and NM-related adverse events. RESULTS: Only 441 of the planned 800 patients were enrolled (non-NM: n = 149; NM: n = 292 [pre-ERCP NM: n = 144; post-ERCP NM: n = 148]). Patient characteristics were balanced at baseline with no significant differences between groups. PEP occurred in 40/441 (9%) patients (non-NM: n = 15 [10%]; NM: n = 25 [9%]), including 17 (12%) and eight (8%) in the pre-ERCP and post-ERCP NM groups, respectively. In the NM group, the incidence of PEP was lower in the low-risk group than in the high-risk group. Pancreatic injection and double-guidewire technique were independent risk factors for PEP. NM-related adverse events of hyperkalemia occurred in two (0.7%) patients. CONCLUSIONS: We found no evidence for the prophylactic effect of NM against PEP, regardless of the timing of administration; however, further studies are needed.

Ulinastatin in the Management of Severe Acute Alcoholic Pancreatitis: A Case Series.

Severe acute alcoholic pancreatitis is a second common form of pancreatitis that requires intensive care unit care and has high morbidity and mortality due to lacking specific treatment. Management of alcoholic pancreatitis is generally non- specific and supportive. We hereby present a case-series of three patients that describes the successful treatment of severe acute alcoholic pancreatitis with ulinastatin and other supportive treatment. From this we want to emphasize that ulinastatin a protease inhibitor can be used in the treatment of alcoholic pancreatitis.

Current usage status of somatostatin and its analogs and trypsin inhibitors: a real-world study of 34,654 Chinese adult patients with acute pancreatitis.

BACKGROUND: Although somatostatin and its analogs and trypsin inhibitors (TSI) are widely recommended for acute pancreatitis (AP), there is a lack of high-quality multicenter trials that validate these drug classes. We aimed to examine the current usage status of somatostatin and its analogs and TSI in Chinese adult AP patients. METHODS: We conducted a retrospective study which collected information for adult patients who were diagnosed with AP from January 1, 2015 to June 30, 2017 at 192 hospitals in China. Subsequently, we conducted a statistical analysis of the baseline information of patients, and revealed the usage of somatostatin, octreotide, ulinastatin, and gabexate. Thereafter, we stratified AP by severity and analyzed the current status of treatment. RESULTS: A total of 34,654 patients were included in this study. Mean age of patients was 49.9 years and 63% were males. Fifty-five percent of mild AP patients opted to receive octreotide, while 53.66% and 64.61% of moderate AP and severe AP patients respectively opted to receive somatostatin. At treatment initiation, somatostatin was mainly prescribed for mild and moderate AP patients, which were 723 and 894 daily defined doses (i.e., defined dose per day for a drug used by every 1,000 patients). Ulinastatin was mainly prescribed for severe AP patients, with a prescription volume of 1,230 daily defined doses. The consumption of ulinastatin in later stages of severe AP treatment was significantly greater than other drugs. CONCLUSIONS: Somatostatin analogs and TSI are widely used as therapeutic drugs for AP treatment in China, with usage beginning at the early stages of the disease and lasting on average for 1 week. Of these drugs, somatostatin and octreotide were identified as the most commonly-used drugs, while ulinastatin was found to be widely used at the late stages of severe AP.

Cytokine storms caused by novel coronavirus 2019 and treatment for cardiac injury.

Since December 2019, an outbreak of a new coronavirus, COVID-19, infection has been taking place. At present, COVID-19 has spread to most countries worldwide. The latest evidence suggests that cytokine storm syndrome (CSS) is an important cause of the transition from mild to critical pneumonia and critically ill patients' death. The sudden exacerbation of COVID-19 may be related to a cytokine storm. Therefore, early identification and active treatment of CSS may play very important roles in improving the patients' prognosis, and these tasks are given attention in the current treatment of new Coronavirus pneumonia. However, there is still no specific medicine for this purpose. This article reviews cytokine storms and conducts an exploratory review of pharmacotherapy for cytokine storms to provide a reference for clinical treatment.

A retrospective study of ulinastatin for the treatment of severe sepsis.

This retrospective study aimed to investigate the efficacy and safety of existing approach of ulinastatin for the treatment of severe sepsis (SS).A total of 130 eligible patients with SS were included in this study. We divided them into an intervention group (n = 65) and a control group (n = 65). Patients in both groups received conventional therapy. In addition, patients in the intervention group received ulinastatin for 7 days. Outcomes were measured by Acute Physiology and Chronic Health Evaluation II (APACHE II), Multiple Organ Failure (MOF), Glasgow Coma Scale (GCS), CD3, CD4, CD8, CD4/CD8, and adverse events. We assessed all outcomes before and after treatment.After treatment, patients in the intervention group showed better improvement in APACHE II (P < .01), MOF (P < .01), GCS (P < .01), CD3 (P = .03), CD4 (P = .03), and CD4/CD8 (P < .01), than those of patients in the control group. There are similar safety profiles between both groups.This study suggests that ulinastatin may be beneficial for SS. Future studies are still needed to warrant the results of this study.

EcTI impairs survival and proliferation pathways in triple-negative breast cancer by modulating cell-glycosaminoglycans and inflammatory cytokines.

Breast cancer is the most common malignant tumor among women worldwide, and triple-negative breast cancer is the most aggressive type of breast cancer, which does not respond to hormonal therapies. The protease inhibitor, EcTI, extracted from seeds of Enterolobium contortisiliquum, acts on the main signaling pathways of the MDA-MB-231 triple-negative breast cancer cells. This inhibitor, when bound to collagen I of the extracellular matrix, triggers a series of pathways capable of decreasing the viability, adhesion, migration, and invasion of these cells. This inhibitor can interfere in the cell cycle process through the main signaling pathways such as the adhesion, Integrin/FAK/SRC, Akt, ERK, and the cell death pathway BAX and BCL-2. It also acts by reducing the main inflammatory cytokines such as TGF-α, IL-6, IL-8, and MCP-1, besides NFκB, a transcription factor, responsible for the aggressive and metastatic characteristics of this type of tumor. Thus, the inhibitor was able to reduce the main processes of carcinogenesis of this type of cancer.

Emerging pharmacological therapies for ARDS: COVID-19 and beyond.

ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure. Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome. Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition. The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS. We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution. We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS. Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing. The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation. Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies 'precision medicines.' It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS.

A prospective observational study to explore the correlation of peripheral arterial pulse/resistance index, organ function, and inflammation in patients with septic shock.

INTRODUCTION: The evaluation of the functional status of blood vessels, especially the arterial system, plays a very important role in the judgment of the condition of septic shock patients and the guidance of resuscitation programs and the judgment of the therapeutic effect. We aimed to design an observational study protocol to explore the correlation of peripheral arterial pulse/resistance index, organ function and inflammation in patients with septic shock. METHODS AND ANALYSIS: A total of 60 patients with septic shock in the Affiliated Hospital of Southwest Medical University from June 2020 to September 2020 and 20 healthy volunteers will be enrolled. Total of 60 patients with septic shock will be randomly divided into 20 groups by lot method. Group 1: fluid resuscitation; Group 2: fluid resuscitation + norepinephrine; Group 3: fluid resuscitation + norepinephrine + ulinastatin; Group 4: healthy control group. Fluid resuscitation is an early goal-directed fluid resuscitation in which norepinephrine is adjusted by a senior intensive care unit specialist for clinical presentation and ulinastatin is pumped at 20,000 U/h. Index including vascular ultrasound, inflammatory factors, organ function will be collected and analyzed. DISCUSSION: Existing studies on septic shock focus on hemodynamics of the heart, brain, and kidney, while the differences in blood flow between peripheral blood vessels and protective renal vessels may be consistent, and imaging analysis is still lacking. This study protocol aims to explore the correlation of peripheral arterial pulsation index/resistance index, organ function, and inflammation in patients with septic shock. TRIAL REGISTRATION: Chinese Clinical trial registry: ChiCTR2000031565.

Perioperation ulinastatin intervention protects liver function in hepatectomy: a systematic review of randomized controlled trials and meta-analysis.

BACKGROUND: Vascular occlusion during hepatectomy accompanies ischemia-reperfusion (IR) injury, which can cause liver dysfunction and affect patients' outcome. Ulinastatin or urinary trypsin inhibitor (UTI), a polyvalent inhibitor of various enzymes, has been confirmed of anti-IR injury effect in recent studies. Here we performed a systematic review and meta-analysis to assess the benefits of perioperation UTI using to protect liver function in hepatectomy. METHODS: Randomized controlled trials (RCTs) evaluating UTI in hepatectomy were identified. Two independent reviewers extracted data on basic characteristics and risk of bias in the studies, and on outcomes such as alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (TBIL) from 1 to 7 days after operation. RESULTS: A total of 9 RCTs including 408 UTI and 372 control participants were identified. There was no significant difference in basic characteristics such as age or sex. The majority of the patients who underwent hepatectomy had primary liver carcinoma, liver metastases and benign liver lesions. A significant improvement in liver function was associated with UTI use not only at 1 and 3 days postoperatively, but also at 7 days (all P≤0.01). However, significant heterogeneity existed between the pooled studies (all P<0.01). CONCLUSIONS: UTI has positive protective effects against IR injury in hepatectomy. However, further highquality RCTs are needed to confirm this conclusion.

Effect of ulinastatin on post-operative blood loss and allogeneic transfusion in patients receiving cardiac surgery with cardiopulmonary bypass: a prospective randomized controlled study with 10-year follow-up.

BACKGROUND: Major bleeding and allogeneic transfusion leads to negative outcomes in patients receiving cardiac surgery with cardiopulmonary bypass (CPB). Ulinastatin, a urine trypsin inhibitor, relieves systemic inflammation and improves coagulation profiles with however sparse evidence of its effects on blood loss and allogeneic transfusion in this specific population. METHODS: In this prospective randomized controlled trial, 426 consecutive patients receiving open heart surgery with CPB were randomly assigned into three groups to receive ulinastatin (group U, n = 142), tranexamic acid (group T, n = 143) or normal saline (group C, n = 141). The primary outcome was the total volume of post-operative bleeding and the secondary outcome included the volume and exposure of allogeneic transfusion, the incidence of stroke, post-operative myocardial infarction, renal failure, respiratory failure and all-cause mortality. A ten-year follow-up was carried on to evaluate long-term safety. RESULTS: Compared with placebo, ulinastatin significantly reduced the volume of post-operative blood loss within 24 h (688.39 ± 393.55 ml vs 854.33 ± 434.03 ml MD - 165.95 ml, 95%CI - 262.88 ml to - 69.01 ml, p < 0.001) and the volume of allogeneic erythrocyte transfusion (2.57 ± 3.15 unit vs 3.73 ± 4.21 unit, MD-1.16 unit, 95%CI - 2.06 units to - 0.26 units, p = 0.002). The bleeding and transfusion outcomes were comparable between the ulinastatin group and the tranexamic acid group. In-hospital outcomes and 10-year follow-up showed no statistical difference in mortality and major morbidity among groups. CONCLUSIONS: Ulinastatin reduced post-operative blood loss and allogeneic erythrocyte transfusion in heart surgery with CPB. The mortality and major morbidity was comparable among the groups shown by the 10-year follow-up. TRIAL REGISTRATION: The trial was retrospectively registered on February 2, 2010. TRIAL REGISTRATION NUMBER: https://www.clinicaltrials.gov Identifier: NCT01060189.

Alpha-1 Antitrypsin Deficiency and Pregnancy.

Alpha-1 Antitrypsin Deficiency (A1AD) is a hereditary condition characterized by low levels of circulating alpha-antitrypsin (AAT) in plasma. It is the best understood genetic risk factor for the development of chronic obstructive pulmonary disease (COPD). The diagnosis of A1AD is under-recognized. While there is a significant heterogeneity in disease presentation in relation to the severity of symptoms and prognosis, it is not uncommon for young individuals, including pregnant women to already have moderate to advanced lung disease at the time of diagnosis. Reductions in AAT levels may have unique implications for a gravid patient beyond that of lung disease. Care of the pregnant A1AD patient with chronic lung disease follows the principles of care for the management of airways disease in general with control of symptoms and reduction in exacerbation risk the main tenets of treatment. The effect of A1AD and augmentation in pregnancy has not been studied and thus care is reliant on expert opinion and clinical experience. Providers caring for pregnant patients with A1AD should consider referral to health care systems and providers with specific expertise in A1AD. Ultimately the decision is left to the individual patient and their physician to weigh the risk benefit of cessation or continuation of therapies. In this review, we present the perinatal course of a woman with A1AD and review the available literature pertaining to AAT and pregnancy and discuss the clinical implications.

The efficacy of different doses of ulinastatin in the treatment of severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is a severe form of inflammatory disease with a high mortality rate. Ulinastatin, a urinary trypsin inhibitor, has anti-inflammatory properties and may be beneficial to critically ill patients with SAP. Nevertheless, there is currently insufficient evidence to conclude whether there is a dose-effect relationship between ulinastatin and SAP treatment outcomes. The present study examined the efficacy of ulinastatin at different doses in the treatment of SAP. METHODS: A retrospective study was conducted examining the clinical outcomes of 130 SAP patients. Patients were categorized into a control group and three groups receiving different daily doses of ulinastatin (200,000; 400,000; and 600,000 IU). The study compared the 1-week mortality rate; the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score; abdominal pain relief time; time to recover a normal heart and respiratory rate; blood amylase, glucose, C-reactive protein, and procalcitonin levels; and white blood cell (WBC) count among the different groups. RESULTS: The 400,000 and 600,000 IU groups had significantly lower mortality rates and WBC count compared to the 200,000 IU group (P<0.05). Furthermore, the 400,000 IU group had a significantly shorter abdominal pain relief time compared to the 200,000 IU group (P<0.05). Compared to the 200,000 IU group, the 600,000 IU group had significantly shorter time to recover a normal respiratory rate and a lower APACHE-II score (P<0.05). CONCLUSIONS: Ulinastatin can improve the clinical outcomes of patients with SAP but efficacy varies with the dosage.

Protective effect of rhubarb combined with ulinastatin for patients with sepsis.

BACKGROUND: Sepsis is the leading cause of death in critically ill patients. Ulinastatin (UTI), a protease inhibitor, and rhubarb, used as a traditional Chinese medication, are proved to be effective in treating sepsis, but the effect of the combination therapy of these two drugs on sepsis remains unclear. This study aimed to investigate the effect of the combination treatment of UTI and rhubarb on sepsis patients. METHODS: A total of 75 septic patients were randomly divided into control group, UTI group, Rhubarb group, and UTI plus Rhubarb group. Clinical data and score of Acute Physiology and Chronic Health Evaluation II (APACHE II) were collected; lymphocyte subtypes in the peripheral blood were analyzed before and after the 5-day treatment in the Intensive Care Unit. RESULTS: All the therapeutic interventions (UTI alone, rhubarb alone, or UTI plus rhubarb) significantly reduced the levels of C-Reactive protein, white blood cell density, lactic acid, and APACH II scores, and elevated the levels of CD4/CD8, but only UTI plus rhubarb treatment obviously decreased the level of procalcitonin. CONCLUSION: This study suggested that the combination of UTI and rhubarb may be a promising therapeutic scheme to ameliorate sepsis.

Ulinastatin reduces postoperative bleeding and red blood cell transfusion in patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Ulinastatin is a type of glycoprotein and a nonspecific wide-spectrum protease inhibitor like antifibrinolytic agent aprotinin. Whether Ulinastatin has similar beneficial effects on blood conservation in cardiac surgical patients as aprotinin remains undetermined. Therefore, a systematic review and meta-analysis were performed to evaluate the effects of Ulinastatin on perioperative bleeding and transfusion in patients who underwent cardiac surgery. METHODS: Electronic databases were searched to identify all clinical trials comparing Ulinastatin with placebo/blank on postoperative bleeding and transfusion in patients undergoing cardiac surgery. Primary outcomes included perioperative blood loss, blood transfusion, postoperative re-exploration for bleeding. Secondary outcomes include perioperative hemoglobin level, platelet counts and functions, coagulation tests, inflammatory cytokines level, and so on. For continuous variables, treatment effects were calculated as weighted mean difference (WMD) and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio and 95% CI. Statistical significance was defined as P < .05. RESULTS: Our search yielded 21 studies including 1310 patients, and 617 patients were allocated into Ulinastatin group and 693 into Control (placebo/blank) group. There was no significant difference in intraoperative bleeding volume, postoperative re-exploration for bleeding incidence, intraoperative red blood cell transfusion units, postoperative fresh frozen plasma transfusion volumes and platelet concentrates transfusion units between the 2 groups (all P > .05). Ulinastatin reduces postoperative bleeding (WMD = -0.73, 95% CI: -1.17 to -0.28, P = .001) and red blood cell (RBC) transfusion (WMD = -0.70, 95% CI: -1.26 to -0.14, P = .01), inhibits hyperfibrinolysis as manifested by lower level of postoperative D-dimer (WMD = -0.87, 95% CI: -1.34 to -0.39, P = .0003). CONCLUSION: This meta-analysis has found some evidence showing that Ulinastatin reduces postoperative bleeding and RBC transfusion in patients undergoing cardiac surgery. However, these findings should be interpreted rigorously. Further well-conducted trials are required to assess the blood-saving effects and mechanisms of Ulinastatin.