Effects of high-dose glucose-insulin-potassium on acute coronary syndrome patients receiving reperfusion therapy:a meta-analysis

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding:A meta-analysis

AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was performed with a fixed effects model or random effects model.RESULTS:Nine eligible RCTs including 1342 patients were retrieved.The results showed that high-dose intravenous PPI was not superior to low-dose intra-venous PPI in reducing rebleeding[odds ratio(OR)= 1.091,95%confidential interval(CI):0.777-1.532],need for surgery(OR=1.522,95%CI:0.643-3.605) and mortality(OR=1.022,95%CI:0.476-2.196).Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients(OR=0.831,95%CI,0.467-1.480)and European patients(OR=1.263,95%CI:0.827-1.929).CONCLUSION:Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.

Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy

AIM To evaluate toxicity and treatment outcome of highdose radiotherapy(RT) for cervical esophageal cancer(CEC).METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage Ⅰ to Ⅲ cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local(occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed.RESULTS Grade 1, 2, and 3 esophagitis occurred in 19(30.6%), 39(62.9%), and 4 patients(6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients(25.8%) developed post-RT stenosis, of which 7 cases(43.8%) were malignant. Four patients(6.5%) developed tracheoesophageal fistula(TEF), of which 3(75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4(P = 0.001), complete circumference involvement(P < 0.0001), stenosis at diagnosis(P = 0.024), and endoscopic complete response(P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis(P = 0.003). A higher dose(≥ 60 Gy) was not associated with occurrence of postRT stenosis or TEF. With a median follow-up of 24.3(range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival(OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement(P = 0.023), stenosis at diagnosis(P < 0.0001), and occurrence of post-RT stenosis or TEF(P < 0.001) in univariate analysis, while stenosis at diagnosis(P = 0.004) and occurrence of post-RT stenosis or TEF(P = 0.023) were significant in multivariate analysis. CONCLUSION Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.

High-dose interferon-α2b induction therapy in combination with ribavirin for treatment of chronic hepatitis C in patients with non-response or relapse after interferon-a monotherapy

AIM： To evaluate the daily high-dose induction therapy with interferon-α2b （IFN-α2b） in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-totreat patient group. METHODS： Seventy patients were enrolled in this study. Treatment was started with 10 NU IFN-α2b daily for 3 wk, followed by IFN-α2b 5 NU/TIW in combination with ribavirin （1 000-1 200 mg/d） for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 （IFN-α2b 3MU/TIW＋1000-1200 mg ribavirin/daily）. RESULTS： The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response （EVR） was achieved in 60% of patients. Fifty percent of all patients achieved an end-oftreatment response （EOT） and d0% obtained a sustained viral response （SVR）. Patients with no response had a significantly lower response rate than those with a former relapse （SVR 30% vs 53%; P=0.049）. Furthermore, lower response rates were observed in patients infected with genotype la/b than in patients with non-1-genotype （SVR 28% vs7d%; P=0.001）. As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus. CONCLUSION： Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.

Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia

Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.

The Experience of Pain and Anxiety in Cervical Cancer Patients Undergoing Multiple Fraction High-Dose Rate Brachytherapy: A Prospective Observational Study

Purpose: To evaluate the anxiety and pain levels of cervical cancer patients undergoing intracavitary multifraction high-dose rate (HDR) brachytherapy, as part of a process to develop guidelines for quality patient-centered care. Methods: Cervical cancer patients (n = 31) undergoingmultiple fraction HDR brachytherapy treatment at the National Institute of Oncology in Rabat (Morocco) completed ratings of pain and anxiety intensity using 11-point verbal analog scales, at 6 key time points over 2 brachytherapy insertion procedures and 4 brachytherapy fractions. Women were evaluated for psychological status at baseline before starting the brachytherapy process using the Hospital Anxiety and Depression Scale (HADS). Scores were grouped as follows: 0 - 7 = normal, 8 - 10 = borderline, 11 - 21 = abnormal. Factors that could affect anxiety levels such as education level, relationship status, number of pregnancies and prior surgical history were documented. Results: Between July and August 2020, 31 women with a median age of 49.6 years were evaluated (range: 27 - 70). The HADS score identified depression in 5 patients (16.1%) and anxiety in 12 patients (38.7%). Throughout both treatment procedures, anticipatory anxiety was reported, with a maximum intensity in the operating room during spinal anesthesia (3.23 ± 1.7) and during applicator insertion (2.97 ± 2.4). Moderate-to-severe anxiety scores were reported in 25.8% and 22.6% of patients respectively. Level of education showed a significant correlation with anxiety scores (p = 0.027). Pain increased significantly during the procedure (p ± 1.4) and applicator removal (4.74 ± 1.5) turned out to be the most painful parts of the procedure. No correlation was found between pain and anxiety levels. Conclusion: Intracavitary multifraction high-dose rate brachytherapy is associated with mild to moderate levels of pain and anxiety, although a subset of patients reported more severe symptoms and may require additional medical and psychological support, with particular emphasis on bed-rest duration and applicator removal. The development of effective interventions (both pharmacological and non-pharmacological) is needed to improve women’s experiences of brachytherapy for locally advanced cervical cancer.

Very-high-dose olanzapine for treatment-resistant schizophrenia

Treatment-resistant schizophrenia has an extremely negative impact on mental health and social life. If clozapine, the gold standard treatment, fails, there are very few options left. The literature suggests that high-dose olanzapine (20 - 60 mg/day) is a possible alternative. We report two cases in which very high doses of olanzapine were administered, with significant clinical improvements above 60 mg/day. Clinical, metabolic and cardiac tolerance was good. This report highlights the usefulness of very-high-dose olanzapine in treatment-resistant schizophrenia. The main hypotheses concerning the psychopharmacological mechanisms of very-high-dose olanzapine are discussed.

Comparison of High-Dose Dexamethasone and Prednisone for Initial Treatment of Adult Primary Immune Thrombocytopenia

Prednisone is the most common first-line treatment for adult primary immune thrombocytopenia (ITP). However, the best initial therapeutic approach is still a matter of debate. Prior studies have shown that high-dose dexamethasone (HD-DXM) produces a high sustained efficacy not achieved by conventional prednisone therapy. However, the definition of response widely differs between individual reports, and this heterogeneity makes comparison of the efficacy difficult. The aim of our study was to compare the therapeutic outcomes of a conventional dose of prednisone with HD-DXM for adult ITP patients as initial therapy. Thirty patients treated with prednisone and 22 patients treated HD-DXM were retrospectively analyzed. No significant differences between the HD-DXM and prednisone groups were observed for the rates of complete response (68% vs. 70%) and response (18% vs. 17%). However, 1 year probability of sustained response was significantly greater in the HD-DXM group than in the prednisone group (78% vs. 38%;P = 0.008). No adverse events necessitating discontinuation of treatment were observed in either group. Our retrospective analysis showed that initial treatment with HD-DXM produced longer response duration compared to a conventional dose of prednisone. Randomized clinical trials are warranted to establish the optimal initial steroid therapy for adult ITP.

A New Variant of Combined Pulmonary Fibrosis and Emphysema from Long-Term High-Dose of Glucocorticoid Therapy: A Case Report

Recent studies have described the combination of both pulmonary emphysema and idiopathic interstitial lung disease (ILDs) by means of high-resolution computed axial tomography (HRCT). Definition of this syndrome was first named by Cottin as combined pulmonary fibrosis and emphysema (CPFE). Functional and radiological findings have showed that these patients are suffering from severe breathlessness, but whose pulmonary functional tests revealed no signs of obstruction, normal static lung volumes, and depressed DLco, most with a history of smoking [1] [2]. The radiological and endoscopic studies especially show that these patients have both areas of upper-lobe predominant emphysema and lesions compatible with fibrosis in both lung bases [3]. No prior research has reported any cases of such condition in person with no prior history of smoking as well as long-term high-dose of glucocorticoid therapy. In this case report, we discuss the presentation, diagnosis, and management of a 53-year-old non-smoker with increasing shortness of breath with a long-term high-dose of glucocorticoid therapy discovered to have an abnormal variant or presentation of CPFE. The cause of disease was attributed to a certain history of smoking in most studies;other potential risk factors have yet to be properly analyzed. This clinical report features a special case about the problem and solution surrounding this issue.

Effects of ulinastatin combined with dexmedetomidine on cognitive dysfunction and emergence agitation in elderly patients who underwent total hip arthroplasty

BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture increases.Hip fracture is a common type of fracture in older people.Total hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint function.AIM To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent THA.METHODS A total of 397 patients who underwent THA from February 2019 to August 2022.We conducted a three-year retrospective cohort study in Shaanxi Provincial People’s Hospital.Comprehensive demographic data were obtained from the electronic medical record system.We collected preoperative,intraoperative,and postoperative data.One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group.One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group.One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin group.The patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were evaluated.RESULTS There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(P<0.05).Compared with the Dex and ulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all P<0.05).Compared with those in the Dex and ulinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of the alertness/sedation score and Ramsay score of the Dex+ulinastatin group were significantly different from those of the Dex and ulinastatin groups on the first day after the operation(all P<0.05).CONCLUSION Ulinastatin combined with Dex can prevent the occurrence of POCD and emergence agitation in elderly patients undergoing THA.

Efficacy and safety of ulinastatin in the treatment of septic shock:a systematic review and meta-analysis

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-α(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-α,Interleukin-6,C reactive protein,hypersensitive C-reactive protein,and procalcitonin levels in the body.

Effect of ulinastatin combined rivaroxaban on deep vein thrombosis in major orthopedic surgery

Objective:To explore the effect of ulinastatin(UTI) continuous infusion combined Rivaroxaban on the deep vein thrombosis in patients undergoing major orthopedic surgery.Methods:Forty-five patients undergoing major orthopedic surgery were randomly divided into three groups:ulinastatin continuous infusion(Uc) group,ulinastatin single injection(Us) group and control(C) group.All patients received patient-controlled intravenous analgesia(PCIA) after operation,and took Rivaroxaban 10 mg orally 12 hours after operation.Ulinastatin(5 000 U/kg)was given intravenously to both Uc and Us groups preoperatively.Group C was given isometric normal saline,group Uc was pumped UTI continuous intravenously at the end of surgery(10 000U/kg) to 48 hours through PCIA pump.The values of hematocrit(HCT),thrombomodulin(TM),Interleukin(IL-6),thrombin-antithrombin complex(TAT),D-Dimer(D-D) were normally tested before surgery(T1),at the end of the surgery(T2),12 hours(T3).24 hours(T4) and 48 hours(T5)after surgery.Results:Compared with T1,there was an upward tendency in TM,IL-6,TAT,and D-D after operation in group C group(P <0.05).The values of them were significandy increased from nearly 24-hour after surgery in Us group(P<0.05).In group Uc.there were no significant changes in these indices after operation(P>0.05).Conclusions:During the perioperative period,ulinastatin continuous infusion combined Rivaroxaban can correct blood hypercoagulability through different approaches in patients undergoing major orthopedic surgery.

Ulinastatin suppresses endoplasmic reticulum stress and apoptosis in the hippocampus of rats with acute paraquat poisoning

Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had dis- appeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-medi- ated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraqnat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.

Ulinastatin for acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis

AIM: To investigate the efficacy and safety of ulinastatin for patients with acute lung injury(ALI) and those with acute respiratory distress syndrome(ARDS).METHODS: A systematic review of randomized controlled trials(RCTs) of ulinastatin for ALI/ARDS was conducted. Oxygenation index, mortality rate [intensive care unit(ICU) mortality rate, 28-d mortality rate] and length of ICU stay were compared between ulinastatin group and conventional therapy group. Meta-analysis was performed by using Rev Man 5.1.RESULTS: Twenty-nine RCTs with 1726 participants were totally included, the basic conditions of which were similar. No studies discussed adverse effect. Oxygenation index was reported in twenty-six studies(1552 patients). Ulinastatin had a significant effect in improving oxygenation [standard mean difference(SMD) = 1.85, 95%CI: 1.42-2.29, P < 0.00001, I2 = 92%]. ICUmortality and 28-d mortality were respectively reported in eighteen studies(987 patients) and three studies(196 patients). We found that ulinastatin significantly decreased the ICU mortality [I2 = 0%, RR = 0.48, 95%CI: 0.38-0.59, number needed to treat(NNT) = 5.06, P < 0.00001], while the 28-d mortality was not significantly affected(I2 = 0%, RR = 0.78, 95%CI: 0.51-1.19, NNT = 12.66, P = 0.24). The length of ICU stay(six studies, 364 patients) in the ulinastatin group was significantly lower than that in the control group(SMD =-0.97, 95%CI:-1.20--0.75, P < 0.00001, I2 = 86%). CONCLUSION: Ulinastatin seems to be effective for ALI and ARDS though most trials included were of poor quality and no information on safety was provided.

Effect of ulinastatin on paraquat-induced-oxidative stress in human type Ⅱ alveolar epithelial cells

BACKGROUND： Ulinastatin （UTI） is a urinary trypsin inhibitor extracted and purified from urine of males. This study aimed to explore the effects of UTI on paraquat-induced-oxidative stress in human type II alveolar epithelial cells. METHODS： The human type II alveolar epithelial cells, A549 cells, were cultured in vitro. The A549 cells were treated with different concentrations of paraquat （200, 400, 600, 800, 1 000, 1 200 pmol/L） and ulinastatin（0, 2 000, 4 000, 6 000, 8 000 U/mL） for 24 hours, the cell viability was measured by cell counting kit-8 and the median lethal concentration was selected. In order to establish an in vitro model of paraquat intoxication and to determine the safe dose of ulinastatin, we calculated LD50 using cell counting kit-8 to determine the survival rate of the cells. A549 cells were divided into normal control group, paraquat group and paraquat＋ulinastatin group. The levels of malondialdehyde （MDA） and myeloperoxidase （MPO） were detected by biochemistry colorimetry, while the level of reactive oxygen spies （ROS） was detected by DCFH-DA assay. RESULTS： The survival rate of A549 cells treated with different concentrations of paraquat decreased in a concentration-dependent manner. Whereas there was no decrease in the survival rate of cells treated with 0-4 000 U/mL ulinastatin. The levels of MDA, MPO, and ROS were significantly higher in the paraquat group than in the normal control group after 24-hour-exposure. And the survival rate of the paraquat＋ulinastatin group was higher than that of the paraquat group, but lower than that of the normal control group. The levels of MDA, MPO, and ROS were lower than those of the paraquat group. CONCLUSION： Ulinastatin can alleviate the paraquat-induced A549 cell damage by reducing oxidative stress.

Prospective experimental studies on the renal protective effect of ulinastatin after paraquat poisoning

BACKGROUND:Paraquat(PQ) is an effective herbicide and is widely used in agricultural production,but PQ poisoning is frequently seen in humans with the lung as the target organ.Currently,there are many studies on lung injury after PQ poisoning.But the kidney as the main excretory organ after PQ poisoning is rarely studied and the mechanisms of this poisoning is not very clear.In this study,we observed the expression of caspase-3 and livin protein in rat renal tissue after PQ poisoning as well as the therapeutic effects of ulinastatin.METHODS:Fifty-four Sprague-Dawley(SD) rats were randomly divided into three experimental groups:control group(group A),paraquat poisoning group(group B) and ulinastatin group(group C),with 18 rats in each group.Rats in group B and group C were administered intragastrically with 80mg/kg PQ,rats in group C were injected peritoneally with 100 000 U/kg ulinastatin once a day,while rats in group A were administered intragastrically with the same volume of saline as PQ.At 24,48,72 hours after poisoning,the expression of livin in renal tissue was detected by Westen blotting,the expression of caspase-3 was detected by immunohistochemistry,and the rate of renal cell apoptosis was tested by TUNEL detection.The histopathological changes were observed at the same time.RESULTS:Compared to group A,the expression of caspase-3 in the renal tissue of rats in groups B and C increased significantly at any time point.Compared with group B,the expression of caspase-3 in renal tissue of rats in group C decreased.Compared with group A,the expression of livin in renal tissue in rats of groups B and C increased significantly at any time point(P<0.01),especially in group C(P<0.01).TUNEL method showed that the rate of renal cell apoptosis index was higher in group B at corresponding time points than in group A(P<0.01),and was lower in group C at corresponding time points than in group B(P<0.01).CONCLUSION:UTI has a protective effect on the renal tissue of rats after paraquat poisoning through up-regulating the expression of livin and down-regulating the expression of caspase-3,but the regulation path still needs a further research.

Effect of ulinastatin on hepatic ischemia-reperfusion injury in rats

Objective To investigate the effect of ulinastatin(UTI)on hepatic ischemia-reperfusion injury in rats.Methods Totally 24 adult Sprague-Dawley rats were randomly divided into 3 groups:sham-operated control group(SO group),ischemia-reperfusion group(I/R group)and ulinastatin group(UTI group).Liver in I/R group underwent 1 h of reperfusion after 30 min of ischemia.In UTI group,UTI(2×104 U/kg)was administered to rats 30 min before modeling.The levels of alanine aminotransferase,aspartate aminotransferase and tumor necrosis factor-alpha(TNF-α)in serum were measured and the levels of nitric oxide and malondialdehyde in liver were determined.The histological changes of liver were observed.Results The levels of alanine aminotransferase,aspartate aminotransferase and TNF-α in serum were significantly increased in I/R group compared with those in UTI group(P<0.05).The levels of nitric oxide and malondialdehyde in liver were significantly higher in I/R group than in UTI group(P<0.05).Histological examination of liver indicated that the damages were more severe in I/R group than in UTI group.Conclusion UTI has the ability to inhibit the production of TNF-α and oxyradical,and ameliorate microcirculatory dysfunction in rats with hepatic ischemia-reperfusion injury.

Effects of Xuebijing Combined with Ulinastatin on Coagulation Function of Sepsis Patients

[Objectives] To study the effects of Xuebijing combined with ulinastatin on coagulation function of sepsis patients. [Methods]Fifty six patients conforming to the diagnosis criteria for sepsis and receiving the treatment from May 2015 to January 2019 were selected. They were randomly divided into treatment group and control group according to the order of treatment. The two groups were treated according to the International Guidelines for Management of Severe Sepsis and Septic Shock( 2012),in which ulinastatin and Xuebijing were added to the treatment group. Before the treatment and on the seventh day after the treatment,both groups of patients were measured for the activated partial thromboplastin time( APTT),fibrinogen( Fi B),platelet( PLT),and prothrombin time( PT) were measured;the treatment status of the both groups was continuously observed for 7 d,and the mechanical ventilation time,ICU hospitalization time,and 30-day survival rate were recorded. [Results] Both FIB and PLT of the treatment group were significantly increased,and both APTT and PT were significantly shortened.Compared with the control group,the difference was statistically significant( P < 0. 05). The mechanical ventilation time and ICU hospitalization time of the treatment group were significantly shorter than that of the control group,and the 30-day survival rate of the treatment group was significantly higher than that of the control group,and the difference was statistically significant( P < 0. 05). [Conclusions]Xuebijing combined with ulinastatin can improve coagulation disorders of sepsis patients.

尿胰蛋白酶抑制剂Ulinastatin对lewis肺癌小鼠肿瘤生长和转移的抑制作用

目的探讨尿胰蛋白酶抑制剂(UTI)在动物模型上抗肿瘤作用。方法选用尿胰蛋白酶抑制剂乌司他丁(Ulinastatin),Lewis肺癌小鼠模型;雄性C57BL/6小鼠40只,接种lewis肿瘤细胞,分成生理盐水组(对照组)、环磷酰胺组(CTX)、Ulinastatin2.5万单位组、Ulinastatin5万单位组、Ulinastatin10万单位组,各8只,接种后第6天,开始腹腔给药,记录皮下瘤长短径变化,做生长曲线;接种14天后处死所有小鼠,统计皮下平均瘤重和肺转移灶个数,使用流式细胞计分析凋亡率(AR)增值百分比(SPF)。结果皮下瘤重依次为(7.92±2.52、0.66±0.50、3.47±1.45、3.08±0.81、1.70±1.05)g,平均肺转移灶依次为(8.625±1.407、1.125±1.126、1.625±1.302、1.00±0.75、0.625±0.74)。CTX组(39.3±4.8)%和Ulinastatin10万单位组(40.2±3.1)%的AR值明显增加,Ulinastatin未见SPF值明显减少。结论Ulinastatin对lewis肺癌小鼠的转移瘤生长和自发性肺转移有抑制作用。

Ulinastatin in the treatment of severe acute pancreatitis:A singlecenter randomized controlled trial

BACKGROUND Severe acute pancreatitis(AP)is one of the most common diseases of the gastrointestinal tract and carries a significant financial burden with high disability and mortality.There are no effective drugs in the clinical management of severe AP,and there is an absence of evidence-based medicine concerning the treatment of severe AP.AIM To explore whether ulinastatin(UTI)can improve the outcome of severe AP.METHODS The present research included patients who were hospitalized in intensive critical care units(ICUs)after being diagnosed with severe AP.Patients received UTI(400000 IU)or placebos utilizing computer-based random sequencing(in a 1:1 ratio).The primary outcome measures were 7-d mortality,clinical efficacy,inflammatory response,coagulation function,infection,liver function,renal function,and drug-related adverse effects were evaluated.RESULTS A total of 181 individuals were classified into two groups,namely,the placebo group(n=90)and the UTI group(n=91).There were no statistically significant differences in baseline clinical data between the two groups.The 7-d mortality and clinical efficacy in the UTI group were remarkably improved compared with those in the placebo group.UTI can protect against hyperinflammation and improve coagulation dysfunction,infection,liver function,and renal function.UTI patients had markedly decreased hospital stays and hospitalization expenditures compared with the placebo group.CONCLUSION The findings from the present research indicated that UTI can improve the clinical outcomes of patients with severe AP and has fewer adverse reactions.