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

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World Journal of Psychiatry 2024年第1期14卷 26-35页

作者： Qi-Fan Huo Li-Juan Zhu Jian-Wei Guo Yan-An Jiang Jing Zhao Department of Anesthesiology Shaanxi Provincial People’s HospitalXi’an 710068Shaanxi ProvinceChina

BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture *** fracture is a common type of fracture in older *** hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint *** 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 *** A total of 397 patients who underwent THA from February 2019 to August *** conducted a three-year retrospective cohort study in Shaanxi Provincial People’s *** demographic data were obtained from the electronic medical record *** collected preoperative,intraoperative,and postoperative *** hundred twenty-nine patients who were administered Dex during the operation were included in the Dex *** hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin *** hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin *** patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were *** 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(Pulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all Pulinastatin 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 th

关键词： ulinastatin Dexmedetomidine Postoperative cognitive dysfunction Inflammatory cytokines Total hip arthroplasty

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

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Neural Regeneration Research 2015年第3期10卷 467-472页

作者： Hai-feng Li Shi-xing Zhao Bao-peng Xing Ming-li Sun Department of Emergency Medicine the First Hospital of Jilin University-the Eastern Division

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.

关键词： nerve regeneration paraquat poisoning rats endoplasmic reticulum stress apoptosis ulinastatin CHOP GRP78 caspase-3 hippocampus reactive oxygen species neural regeneration

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

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Medical Data Mining 2024年第1期7卷 1-9页

作者： Chao Tong Aheyeerke Halengbieke Teng-Rui Cao Xin Huang Jia-Lu Luo Jia-Xin Li Xue-Tong Ni Feng Sun Xing-Hua Yang School of Public Health Capital Medical UniversityBeijing 100069China Department of Epidemiology and Biostatistics School of Public HealthPeking University Health Science CenterBeijing 100191China

Background:Septic shock is a common systemic inflammatory response syndrome for critical patients in the intensive care *** is currently used for the treatment of septic *** study sought to evaluate the efficacy and safety of ulinastatin in the treatment of septic shock ***: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 *** 16.0 software was used to conduct the ***: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 Pulinastatin 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 ***,it also lowers TNF-α,Interleukin-6,C reactive protein,hypersensitive C-reactive protein,and procalcitonin levels in the body.

关键词： effectiveness meta-analysis randomized controlled trial septic shock ulinastatin

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Treatment of patients with severe sepsis using ulinastatin and Thymosin al： a prospective, randomized, controlled pilot study

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Chinese Medical Journal 2009年第8期122卷 883-888页

作者： CHEN Hao HE Ming-yan LI Yu-min The Key Laboratory of Organ Transplantation of Public Health Ministry First Affiliated Hospital College of Medicine Zhejiang University Hangzhou Zhejiang 310003 China Department of General Surgery First Hospital of Lanzhou University Lanzhou Gansu 730000 China Department of General Surgery Second Hospital of Lanzhou University Lanzhou Gansu 730000 China

Background Tradition treatment of sepsis and new therapies, including high dose corticosteroids and non-steroidal anti-inflammatory drugs, have proven unsuccessful in improving survival. This study aimed to evaluate the potential efficacy of immunomodulating therapy using ulinastatin （UTI） plus Thymosin al （Tal） for improving organ function and reducing mortality in patients with severe sepsis. Methods A prospective study was carried out with randomized and controlled clinical analysis of 114 patients conforming to the enrollment standard. All patients had severe sepsis and received standard supportive care and antimicrobial therapy. Fifty-nine patients were also administered UTI plus Tal （defined as Group A）, 55 patients were given a placebo （defined as Group B）. Clinical parameters were determined by evaluation with the Acute Physiology and Chronic Health Evaluation II （APACHE II）, multiple organ failure （MOF） and the Glasgow Coma Scores （GCS） on entry and after therapy on the 3rd, 8th, and 28th day. By flow cytometery and ELISA lymphocyte subsets and cytokines were analyzed. Survival analysis was determined by the Kaplan-Meier method at 28, 60, and 90 days. Results Based on comparison of the two groups, patients in Group A exhibited a better performance in organ failure scores which was noticeable soon after initiation of treatment. Patients in Group A also demonstrated a better resolution of pre-existing organ failures during the observation period. After initiation of treatment, significant improvements in the CD4^＋/CD8^＋ ratio, a quicker balance between proinflammatory mediators such as tumor necrosis factor a, interleukin 6 and anti-inflammatory cytokines including interleukin 4 and interleukin 10 were found. This was followed by cumulative survival increases of 17.3% at 28 days, 28.9% at 60 days, and 31.4% at 90 days in Group A. The reduction in mortality was accompanied by a considerably shorter stay in the ICU and a shorter length of supportive ventilation

关键词： ulinastatin Thymosinal severe sepsis immunomodulatory therapy

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Combined therapy with methylprednisolone and ulinastatin in experimental autoimmune encephalomyelitis

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Chinese Medical Journal 2013年第18期126卷 3439-3445页

作者： SHU Ya-qing YANG Yu WANG Yu-ge DAI Yong-qiang XIAO Li QIU Wei LU Zheng-qi WU Ai-ming RUAN Heng-fang HU Xue-qiang Multiple Sclerosis Center Department of Neurology the Third Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong 510630 China

Background Our previous study had demonstrated that ulinastatin （UTI） had a neuroprotective effect in experimental autoimmune encephalomyelitis （EAE）. Methylprednisolone has been recommended to be a standard drug in multiple sclerosis （MS） therapies. The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE. Methods Mice were divided into a UTI treatment group, a methylprednisolone treatment group, a combined treatment group with UTI and methylprednisolone, a normal saline treatment group, and a normal control group. EAE mice were induced in groups receiving different combined treatments, or respective monotherapies. Demyelination was evaluated by Solochrome cyanin staining. 2＇,3＇-cyclic nucleotide 3＇- phosphodiesterase （CNP）/myelin basic protein （MBP）/the precursor form of nerve growth factor （proNGF）/p75/inducible nitric oxide synthase （iNOS） proteins in cerebral cortex of EAE were detected by Western blotting. Results The combined treatment group had a lower clinical score （0.61±0.06） and demyelinating score （1.33±0.33） than the groups with normal saline （clinical score： 1.39±0.08, P 〈0.001; demyelinating score： 2.75±0.49, P 〈0.05） or monotheraphies. Compared with the saline treated EAE group, UTI combined methylprednisolone significantly increased expressions of CNP （1.14±0.06 vs. 0.65±0.04, P 〈0.001）, MBP （1.28±0.14 vs. 0.44±0.17, P 〈0.001）, and decreased expressions of proNGF （1.08±0.10 vs. 2.32±0.12, P 〈0.001）, p75 （1.13±0.13 vs. 2.33±0.17, P 〈0.001）, and iNOS （1.05±0.31 vs. 2.17±0.13, P 〈0.001） proteins in EAE. Furthermore, UTI combined methylprednisolone could significantly upregulate MBP （1.28±0.14 vs. 1.01±0.15, P 〈0.05） expression and downregulate iNOS （1.05±0.31 vs. 1.35±0.14, P 〈0.05） expression compared to methylprednisolone treatment EAE group. And proNGF expression was significantly lower in combined treatment （1.08±0.10） than that in UTI （1.51±0.24, P 〈0.05） or methylprednisolone （1.31±0.04, P 〈0.05） trea

关键词： ulinastatin methylprednisolone combined therapy experimental autoimmune encephalomyelitis neuroprotection

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

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World Journal of Clinical Cases 2023年第19期11卷 4601-4611页

作者： Su-Qin Wang Wei Jiao Jing Zhang Ju-Fen Zhang Yun-Na Tao Qing Jiang Feng Yu Department of General Surgery The 904^(th) Hospital of Joint Logistic Support ForceWuxi 214044Jiangsu ProvinceChina Department of Nursing The 904^(th) Hospital of Joint Logistic Support ForceWuxi 214044Jiangsu ProvinceChina Department of Neurosurgery The 904^(th) Hospital of Joint Logistic Support ForceWuxi 214044Jiangsu ProvinceChina

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 *** 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 *** To explore whether ulinastatin(UTI)can improve the outcome of severe *** The present research included patients who were hospitalized in intensive critical care units(ICUs)after being diagnosed with severe *** 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 *** 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 *** 7-d mortality and clinical efficacy in the UTI group were remarkably improved compared with those in the placebo *** can protect against hyperinflammation and improve coagulation dysfunction,infection,liver function,and renal *** patients had markedly decreased hospital stays and hospitalization expenditures compared with the placebo *** The findings from the present research indicated that UTI can improve the clinical outcomes of patients with severe AP and has fewer adverse reactions.

关键词： ulinastatin 7-day mortality Severe acute pancreatitis Randomized controlled trial Outcome

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Effect of ulinastatin on the inflammatory response after video-assisted thoracic lobectomy in patients with lung cancer:a randomized controlled study

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Chinese Medical Journal 2022年第7期135卷 806-812页

作者： Won Jung Hwang Min A.Joo Jin Joo Department of Anesthesiology and Pain Medicine Seoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoulRepublic of Korea

Background:The first-line treatment for lung cancer is surgical resection,and one-lung ventilation(OLV)is the most basic anesthetic management method in lung *** OLV,inflammatory cytokines are released in response to the lung tissue damage and promote local and contralateral lung damage through the systemic *** designed a randomized,prospective study to evaluate the effect of the urinary trypsin inhibitor(UTI)ulinastatin on the inflammatory response after video-assisted thoracic lobectomy in patients with lung ***:Adult patients aged 19 to 70 years,who were scheduled for video-assisted thoracic lobectomy surgery to treat lung cancer between May 2020 and August 2020,were enrolled in this randomized,prospective ***(300,000 units)mixed with 100 mL of normal saline in the ulinastatin group and 100 mL of normal saline in the control group was administered over 1 h after inducing ***:The baseline(T0)interferon-γ(IFN-γ)/interleukin-4(IL-4)ratio was not different between the groups(6941.3±2778.7vs.6954.3±2752.4 pg/mL,respectively;P>0.05).The IFN-γ/IL-4 ratio was significantly higher in ulinastatin group at 30 min after entering the recovery room than control group(20,148.2±5054.3vs.6674.0±2963.6,respectively;adjustedP<0.017).Conclusion:Administering UTI attenuated the anti-inflammatory response,in terms of INF-γexpression and the IFN-γ/IL-4 ratio,after video-assisted thoracic surgery in lung cancer *** registration:Clinical Research Information Service of Korea National Institute of Health(CRIS),KCT0005533.

关键词： ulinastatin Lung cancer Video-assisted thoracic surgery INF-γ IL-4

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Effects of serum of the rats ventilated with high tidal volume on endothelial cell permeability and therapeutic effects of ulinastatin

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Chinese Medical Journal 2006年第16期119卷 1374-1380页

作者： HUO Guo-dong CAI Shao-xi CHEN Bo CHEN Ying-hua Department of Respiration Nanfang Hospital Southern Medical University Guangzhou 510515 China

Background With the widespread use of ventilators in treating critically ill patients, the morbidity of ventilator-induced lung injury （VILI） is increasing accordingly. VILI is characterized by a considerable increase in microvascular leakiness and activation of inflammatory processes. In this study we investigated the effects of inflammatory mediators in VILI rat serum on endothelial cytoskeleton and monolayer cellular permeability, as well as the therapeutic effect of ulinastatin, to explore the pathogenesis and the relationship between biotrauma and lung oedema induced by VILI. Methods Thirty healthy male Sprague-Dawley rats were randomly divided into three groups： group A （normal tidal volume ventilation）, group B （high tidal volume ventilation） and group C （high tidal volume ventilation plus ulinastatin）. The serum of each rat after ventilation was added to endothelial cell line ECV-304 medium for two hours to observe the effects of serum and/or ulinastatin on endothelial fibrous actin and permeability. Results Compared to rats ventilated with normal tidal volume, serum of rats ventilated with high tidal volume caused a striking reorganization of actin cytoskeleton with a weakening of fluorescent intensity at the peripheral filament bands and formation of the long and thick stress fibres in the centre resulting in endothelial contraction and higher permeability. Prior treatment with ulinastatin lessened the above changes significantly. The changes of permeability coefficient of endothelial permeability after group A, B or C rats serum stimulation were （6.95 ± 1.66）%, （27.50±7.77）% and （17.71±4.66）% respectively with statistically significant differences （P〈0.05） among the three groups. Conclusions The proinflammatory mediators in the serum of the rats given high tidal volume ventilation increases endothelial permeability by reorganizing actin cytoskeleton, and pretreatment with ulinastatin lessens the permeability by inhibiting of proinflammatory mediator

关键词： ventilation proinflammatory mediators cytoskeleton permeability ulinastatin

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Effect of ulinastatin donor-pretreatment on liver graft during cold preservation in rats

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Chinese Medical Journal 2011年第4期124卷 574-580页

作者： MAO Jie ZHANG Lin SONG Ai-lin CHEN Xiao ZHANG You-cheng Department of General Surgery Lanzhou University Second Hospital Lanzhou Gansu 730030 China

Background Donor-pretreatment with ulinastatin may influence the liver graft during cold preservation. The aim of this research was to determine whether pretreatment of donor liver with ulinastatin can attenuate cold preservation injury,and to explore the mechanism by which ulinastatin affects the donor liver *** One hundred and forty-four Wistar rats were divided into the ulinastatin treatment group （T group） pretreated with ulinastatin 50 000 U/kg and control group （C group） treated with 0.9% normal saline via peritoneal injection prior to the anesthetization. After the abdominal cavity was opened and perfused with cold Ringer＇s lactate solution, the liver was harvested. The harvested liver was preserved in cold Ringer＇s lactate solution for 0, 2, 6, 24 hours, at which time the liver tissue was sampled for determination of dry weight and wet weight, Na＋-K＋-ATPase and Ca2＋-ATPase activity, lactic acid dehydrogenase （LDH） activity, lactic acid and malondialdehyde levels. Light microscopy and electron microscopy were used to observe liver morphology. The liver cold-preservation solution was taken for measurement of aspartate aminotransferase （AST） and alanine transaminase （ALT） levels. Correlation between ATPase activity and lactic acid level was analyzed by SPSS 13.0 for *** The morphology in the T group had improved cell boundaries vs. The C group at each time point. Dry weight to wet weight in the T group was lower than in the C group at 6 hours （P 〈0.05）, but the difference was not significant at 24 hours. ALT levels in the T group were lower than that in the C group at 6 hours （P 〈0.05） and 24 hours （P 〈0.01）. AST levels in the T group were lower than those in the C group at 2 hours （P〈0.05）, 6 hours （P 〈0.01） and 24 hours （P 〈0.01）.Na＋-K＋-ATPase activity in the T group was higher than in the C group and the mean difference between two groups was significant at 0 hour （P 〈0.05） and 2 hours （P 〈0.05）. Ca2＋-ATPase activity in the T group was

关键词： ulinastatin donor pretreatment liver graft cold preservation injury

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Protective effects of hemin pretreatment combined with ulinastatin on septic shock in rats

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Chinese Medical Journal 2008年第1期121卷 49-55页

作者： YU Jian-bo YAO Shang-long Department of Anesthesiology Tianjin Nankai Hospital Tianjin300100 China Department of Anesthesiology Union Hospital Tongji MedicalCollege Huazhong University of Science and Technology WuhanHubei 430022 China

Background Urinary trypsin inhibitor inhibits the enhanced production of pro-inflammatory molecules. Hemeoxygenase-1 induction protects against ischemia/repeffusion injury, oxidative stress, inflammation, transplant rejection, apoptosis, and other conditions. However, it is unknown if a combined hemin and ulinastatin pretreatment could result in protective effects for septic shock. In this study, we investigated the role of hemin pretreatment combined with ulinastatin on septic shock in rats. Methods Eighty healthy, male Sprague-Dawley rats were randomly divided into four groups： group S, group H, group U and group HU. Groups S and U received 1 ml normal saline intraperitoneally, while groups H and HU both received 1 ml （100 mg/kg） hemin. Twenty-four hours later, 0.5 ml （10 mg/kg） E. coil lipopolysaccharide was injected intravenously to replicate the experimental model of septic shock. After an initial 25% decrease in the mean arterial pressure, corresponding to time point 0, groups HU and U received 0.5 ml 10 000 U/kg ulinastatin intravenously, and the others received 0.5 ml normal saline. Results The number of deaths in groups H and U was lower than that in the group S （P〈0.05）, and was higher than that in group HU （all P〈0.05） respectively. The mean arterial pressure （MAP） in the group S was significantly greater than that in group H （P〈0.05）, and was lower than that in group HU and group U （P〈0.05）. The plasma levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, creatinine （Cr） and blood urea nitrogen （BUN）, the malondial- dehyde （MDA） of liver, kidney and lung, and the lung Evans blue （EB） contents in groups H and U, were greater than that in group HU （all P〈0.05）, and were lower than that in group S （all P〈0.05）. In contrast, the plasma levels of CO in groups H and HU were higher than that in groups S and U （all P〈0.05）, and SOD of liver, kidney and lung in groups H and U were higher than that in group S, and were lower than that in grou

关键词： hemin ulinastatin septic shock heme oxygenase carbon oxide

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