1.Ulinastatin protects intestinal mucosal barrier by inhibiting the activation of intestinal NLRP3 inflammasomes in septic rats
Xiang LI ; Chunbo YANG ; Tayier GULIFEIRE ; Yi WANG ; Xiangyou YU
Chinese Critical Care Medicine 2021;33(2):192-197
Objective:To explore the damage of the intestinal mucosal barrier of septic rats by the activation of NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasomes and the role of Ulinastatin (UTI) on the expression of intestinal nuclear factor-κB (NF-κB)/NLRP3 inflammasome signaling pathway in septic rats.Methods:According to the random number table method, 64 male Wistar rats were divided into sham operation group (Sham group), cecal ligation and puncture (CLP) group, UTI treatment group (100 kU/kg UTI was intraperitoneally injected 1, 6, 12 and 18 hours after CLP), and UTI pretreatment group (100 kU/kg UTI was given 1 hour before CLP), with 16 rats in each group. The survival of rats was observed after 24 hours, and the blood was collected from abdominal aorta at 24 hours after modeling, then rats were killed and their ileum tissues were taken. Hematoxylin-eosin (HE) staining was used to observe histopathological changes and Chiu score. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and intestinal fatty acid binding protein (I-FABP) in serum were detected by enzyme linked immunosorbent assay (ELISA). The protein expression of NF-κB p65 in intestinal tissue was detected by Western blotting. The expression of intestinal tight junction proteins Claudin-1, Occludin and the inflammasome NLRP3, apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 were detected by immunohistochemistry.Results:Compared with Sham group, the 24-hour survival rate of CLP group was significantly reduced. Histopathological results showed that the CLP group had severe edema of mucosa and submucosal stroma with obvious infiltration of inflammatory cells and disordered villi arrangement. Some glands were incomplete, and the villus structure was severely damaged. The Chiu score was significantly increased. The levels of TNF-α, IL-1β, I-FABP in serum and the protein expression of NF-κB p65 in intestinal tissue were significantly increased. The positive expressions of NLRP3, caspase-1 and ASC were also significantly increased. However, the positive expression of tight junction protein in small intestine tissue such as Occludin and Claudin-1 were significantly reduced. It suggested that when sepsis occurs, small intestinal mucosal barrier dysfunction happens, and mucosal permeability increases, while tight junction protein expression decreases, NLRP3 inflammasome and its upstream molecule NF-κB p65 were activated. After UTI treatment and UTI pretreatment intervention, although there was no significant difference in 24-hour survival compared with CLP group (62.5%, 68.8% vs. 43.8%, both P > 0.05), the intestinal tissue damage of septic rats was significantly improved. Specifically: Chiu score and the levels of TNF-α, IL-1β, I-FABP in serum were significantly decreased [Chiu score: 3.37±0.25, 3.23±0.16 vs. 4.08±0.13, TNF-α (ng/L): 147.62±20.74, 140.71±24.81 vs. 222.82±16.84, IL-1β (ng/L): 80.64±5.68, 78.11±4.75 vs. 133.73±3.92, I-FABP (μg/L): 38.29±3.60, 35.88±4.52 vs. 59.81±4.66, all P < 0.05]; the protein expression of NF-κB p65 was significantly decreased (NF-κB p65/β-actin: 0.65±0.10, 0.69±0.11 vs. 0.99±0.10, both P < 0.05), the positive expressions of Claudin-1 and Occludin in the small intestine tissue were increased [Claudin-1 positive expression area: (19.43±3.08)%, (23.99±6.27)% vs. (7.77±2.03)%; Occludin positive expression area: (19.58±4.75)%, (23.28±3.68)% vs. (11.69±4.30)%, all P < 0.05], while the positive expressions of NLRP3, caspase-1, ASC were decreased [NLRP3 positive expression area: (7.80±3.14)%, (6.86±2.63)% vs. (14.44±3.68)%; caspase-1 positive expression area: (10.62±3.52)%, (9.49±3.09)% vs. (26.69±8.05)%; ASC positive expression area: (9.95±2.81)%, (10.53±3.61)% vs. (24.16±5.48)%, all P < 0.05]. However, there was no significant difference in the improvement effect between UTI treatment group and UTI pretreatment group.Conclusions:Intestinal barrier dysfunction in sepsis may be related to the activation of NLRP3 inflammasomes in the intestinal mucosa. The protective effect of UTI in the intestinal mucosa may be related to inhibiting the activation of NLRP3 inflammasomes in the intestinal mucosa, but UTI pretreatment has no obvious advantage compared with UTI treatment.
2.Effect of angiotensin 1-7 on renal tubulointerstitial fibrosis of diabetic rats
Xiangyou LI ; Guohua DING ; Yuanyu XIA ; Xinghua CHEN ; Wei LIANG
Chinese Journal of Nephrology 2012;(10):798-803
Objective To investigate the effects of angiotensin1-7 (Ang1-7) on renal tubulointerstitial fibrosis of diabetic rats.Methods Thirty-two male Wistar rats were randomly divided into four groups: normal control group,diabetic group,telmisartan group,Ang1-7-treated group.For 9 weeks after diabetes mellitus model established,24 h proteinuria,urine NAG/Cr,glucose,insulin,TG,TC,BUN,Scr,Na+ and K+ were assessed.Renal pathological changes were evaluated by PAS staining; Expression of TGF-β1,PPARγ and α-SMA mRNA was deteeted by real-time PCR; Protein levels of PPARγ,α-SMA and TGF-β1 were detected by Western blotting.Results (1)At the end of the ninth week,the blood pressure,proteinuria,renal weight/body weight in group DM were significantly higher than those in group NC (P<0.05).(2)Renal interstitial fibrosis in group DM was obviously severe as compared to group NC (P<0.05),but was improved in group TM and group T(P<0.05).(3)TGF-β1 and α-SMA mRNA in group DM were significantly increased,and PPARγ mRNA was significantly decreased.Compared with group DM,TGF-β1 and α-SMA mRNA were significantly decreased,and PPARγ mRNA was significantly increased in group TM and group T,especially in group T.(4)TGF-β1 and α-SMA in group DM were significantly increased,and PPARγ decreased significantly.Compared with group DM,TGF-β1 and α-SMA decreased significantly,PPARγ increased significantly in group TM and group T,especially in group T.Conclusion Ang1-7 inhibits high glucose-induced α-SMA expression in vivo through up-regulating the PPAR expression and may inhibit renal tubulointerstitial fibrosis of diabetic rats.
3.Effect of angiotensin 1-7 on human renal proximal tubular epithelial cell transdifferentiation induced by high glucose and its mechanism
Xiangyou LI ; Guohua DING ; Fengqi HU ; Wei LIANG ; Zhilong REN
Chinese Journal of Nephrology 2011;27(12):903-906
Objective To investigate the effect of angiotensin 1-7(Ang 1-7) on renal proximal tubular epithelial cell(HK-2) transdifferentiation induced by high glucose.Methods All the raised HK-2 cells were divided into 5 groups: normal control group,high glucose group,high glucose with Ang1-7 group,high glucose with Ang1-7 and A779 group,high glucose with pioglitazone group.Expression of peroxisome proliferator activated receptor-γ(PPAR-γ) and α-smooth muscle actin(α-SMA) was detected by Western blotting,real-time PCR and immunofluorescence.Results The levels of PPAR-γ protein and mRNA in HK-2 cells were significantly increased after treatment with high glucose and Ang 1-7.Expression of α-SMA protein and mRNA was inhibited remarkably after treatment with high glucose and Ang 1-7.These effects of Ang 1-7 on HK-2 cells could be reversed by Mas receptor antagonist A779.Conclusion Ang 1-7 inhibits high glucose-induced expression of o-SMA in HK-2 cells,which is in part through the Mas.
4.A survey of present basic constructive situation of intensive care units in second and tertiary grade hospitals in Xinjiang Uygur Autonomous Region
Yi WANG ; Xiaojing XI ; Hua ZHONG ; Yunlin SONG ; Xiaopeng LI ; Qingli DOU ; Xiangyou YU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2015;22(3):317-321
Objective To collect the data of present basic constructive situation of intensive care units (ICUs) in second and tertiary grade hospitals in Xinjiang Uygur Autonomous Region and to provide a data base beneficial to the construction of ICUs in the whole region.Methods The information including basic situation of ICUs in a total of 49 second and tertiary grade hospitals as samples in Xinjiang Uygur Autonomous Region were investigated by questionnaire survey from December 2012 to April 2013. The contents of questionnaire chiefly included the basic situations of hospitals, ICU constructions, ICU human resources and allocation of equipments.Results Forty-nine questionnaires were sent out, and all of them gave answers, the recovery rate being 100%. In the whole region of Xinjiang, there were 49 second and tertiary grade hospitals with establishment of 66 various types of ICUs. ① Medical unit basic situation: the second grade A hospitals accounted for 59.2%, and the tertiary grade A hospitals, 34.7%. There was a larger proportion of local hospitals (67.3%); most of the hospitals had beds over 500 (57.14%), the designed hospital bed number was 41 403, and 35 442 beds were open up for service (85.60%). ② The ICU basic construction situation: the construction of ICUs concentrated mainly after the year 2000, from 2000 to 2010, a total of 37 units, and from 2010 to 2012, 12 units were constructed; when they opened to the public, the beds were relatively few, and the ICUs containing less than 10 beds occupied 79.00%. In the 66 ICUs surveyed, there were 43 general ICUs, accounting the largest proportion, followed by 7 emergency ICUs, and the least were 1 neurosurgery and 1 cardiac surgery ICU. In the 66 ICUs, all together 765 beds were prepared, but actually 808 beds were opening up to public; most of ICUs had 5 - 20 beds, accounting for 71% in all the ICUs. At present, in the whole Xinjiang region, the rate of beds in ICUs in various grades of hospitals opening to the outside for use accounted for more than 80% of which 56% ICUs were almost turning round fully. ③ ICU human resources situation: totally, there were 484 doctors in ICUs in the whole region, the ratio of full-time doctor to nurses was 1:3.50, the ratio for bed to physician 1:0.55 and the ratio for bed to nurse 1:0.92. The title of doctor was primarily resident, and the various title gradient levels were good. Most doctors graduated from a regular medical college, and the doctors having obtained a master degree were few. The physician professional backgrounds were mainly critical disease medicine, emergency medicine and respiratory medicine, the professional relevance being good; the chief way of ICU physicians to engage in advanced study of their professional training was in China, and generally they joined professional continuing education programs poorly, mostly joining once a year or non at all. The physicians who obtained the identification of Chinese critical care medicine specialist accounted only for 23.56%. ④ ICU equipment allocation situation: according to the requirements of ICU construction guidelines, the equipments must be allocated including bedside monitors (703 units), ventilators (516 units) and infusion pumps (702 units), occupying the highest proportion. In the optional equipments, there were enteral nutritional pump (89 stations), blood glucose monitoring device (57 units) and anti-decubitus mattresses (54 units), the proportion being the largest, bispectral index monitor (2 units), extracorporeal membrane oxygenation (ECMO, 1 table) and gastric mucosal carbon dioxide tension pHi meter (0 unit), the proportion being the least or non at all.Conclusions In the whole Xinjiang region, the construction of ICUs is still at the developing stage, and needs to further strengthen the standardized construction. The human resources, equipments, etc. are not distributed in balance, and it is necessary to move forward the adjustment to benefit the development of ICUs in the whole region.
5.Quantitative Analysis of Soil by Laser-induced Breakdown Spectroscopy Using Genetic Algorithm-Partial Least Squares
Xiaoheng ZOU ; Zhongqi HAO ; Rongxing YI ; Lianbo GUO ; Meng SHEN ; Xiangyou LI ; Zemin WANG ; Xiaoyan ZENG ; Yongfeng LU
Chinese Journal of Analytical Chemistry 2015;(2):181-186
Laser-induced breakdown spectroscopy ( LIBS) was used to detect the compositions of soil in the air, and the quantitative analysis model with genetic algorithm-partial least squares ( GA-PLS ) was established. A total of fifty-eight soil samples were split into calibration, monitoring and prediction sets. Eleven soil compositions including Mn, Cr, Cu, Pb, Ba, Al2 O3 , CaO, Fe2 O3 , MgO, Na2 O, and K2 O were quantitatively analyzed. The results demonstrated that, as a pretreatment method for optimizing the selection of spectral lines, GA could be effectively used to reduce the number of spectral lines for use in building PLS model, and hence simplify the quantitative analysis model. More importantly, for most of the soil compositions, GA-PLS could significantly improve the prediction ability compared with the conventional PLS model. Take Mn as an example, the root-mean-square error of prediction ( RMSEP ) was decreased from 0. 0215% to 0 . 0167%, and the mean percent prediction error ( MPE ) was decreased from 8 . 10% to 5 . 20%. The research provides an approach for further improving the accuracy of LIBS quantitative analysis in soil.
6.Construction and analysis of early warning and prediction model for risk factors of sepsis-associated encephalopathy
Li ZHANG ; Xiangyou YU ; Long MA ; Yi WANG ; Xiang LI ; Yanjie YANG
Chinese Critical Care Medicine 2024;36(2):124-130
Objective:To investigate the epidemiological characteristics of sepsis-associated encephalopathy (SAE) in patients with sepsis, analyze its risk factors and build a prediction model, which provides evidence for early clinical identification of SAE patients and improvement of clinical outcomes.Methods:A retrospective observational study was conducted. Sepsis patients admitted to the critical care medical center of the First Affiliated Hospital of Xinjiang Medical University from February 2022 to February 2023 were enrolled. According to whether SAE occurred, the patients were divided into sepsis group and SAE group. The 24 patients without sepsis in the same period were used as controls (non-sepsis group). Demographic data, relevant scores and laboratory test indicators at admission to intensive care unit (ICU), and prognostic indicators were collected. Univariate and multivariate Logistic regression analysis was used to analyze the risk factors for sepsis and SAE. Receiver operator characteristic curve (ROC curve) was drawn. The predictive value of each risk factor for sepsis and SAE.Results:A total of 130 patients with sepsis were included, of which 52 had SAE, and the incidence of SAE was 40.00%. There were significant differences in the length of ICU stay and total length of stay among all groups, while there were no significant differences in hospitalization cost and mechanical ventilation time. Multivariate Logistic regression analysis showed that pulmonary infection [odds ratio ( OR) = 46.817, 95% confidence interval (95% CI) was 5.624-389.757, P = 0.000], acute physiology and chronic health evaluation Ⅱ (APACHEⅡ: OR = 1.184, 95% CI was 1.032-1.358, P = 0.016), sequential organ failure assessment (SOFA: OR = 9.717, 95% CI was 2.618-36.068, P = 0.001), Charson comorbidity index (CCI: OR = 4.836, 95% CI was 1.860-12.577, P = 0.001), hemoglobin (Hb: OR = 0.893, 95% CI was 0.826-0.966, P = 0.005), glutamyltranspeptidase ( OR = 1.026, 95% CI was 1.008-1.045, P = 0.006) were independent risk factors for sepsis in ICU patients. Pulmonary infection ( OR = 28.795, 95% CI was 3.296-251.553, P = 0.002), APACHEⅡ score ( OR = 1.273, 95% CI was 1.104-1.467, P = 0.001), SOFA score ( OR = 8.670, 95% CI was 2.330-32.261, P = 0.001), CCI ( OR = 5.141, 95% CI was 1.961-13.475, P = 0.001), Hb ( OR = 0.922, 95% CI was 0.857-0.993, P = 0.031), glutamyltranspeptidase ( OR = 1.020, 95% CI was 1.002-1.038, P = 0.030) were independent risk factors for SAE in sepsis patients. ROC curve analysis showed that the area under the curve (AUC) of pulmonary infection, APACHEⅡ score, SOFA score, CCI, Hb, and glutamyltranspeptidase for predicting sepsis were 0.792, 0.728, 0.987, 0.933, 0.720, and 0.699, respectively; the AUC of the combined prediction of the above 6 variables for sepsis was 1.000, with a sensitivity of 100% and a specificity of 100%. The AUC predicted by pulmonary infection, APACHEⅡ score, SOFA score, CCI, and Hb for SAE were 0.776, 0.810, 0.907, 0.917, and 0.758, respectively; the AUC of the combined prediction of the above 5 variables for SAE was 0.975, with a sensitivity of 97.3% and a specificity of 93.1%. Conclusions:Sepsis is more severe when accompanied by encephalopathy. Pulmonary infection, Hb, APACHEⅡ score, SOFA score and CCI were independent risk factors of SAE. The combination of the above five indicators has good predictive value for early screening and prevention of the disease.
7.Research based on the e-ICU merge bundle care as the hospital management mode for key indicators devoted to improve the medical quality
Li ZHANG ; Jing GAO ; Fang HOU ; Yi WANG ; Xiangyou YU
Chinese Journal of Practical Nursing 2018;34(15):1144-1149
Objective To discuss the quality improvement effect of the video monitoring management model based on digital ICU for the centralized monitoring of the ICU key index. Methods Selected the ICU key monitoring indicators developed cluster monitoring bundle, using digital ICU monitoring system and clinical management combining synchronous quality supervision and management, developed targeted measures to improve and supervise the implementation, in order to improve the medical quality. Based on the digital ICU in our hospital ICU implementation of key indicators of cluster monitoring and management information for first months the baseline data were compared before and after each index improvement and effect. Results Compared with the pre- implementation period and the baseline survey period, the monitoring times continued to increase by 6 times compared with the baseline. The overall correct implementation rate of the centralized monitoring bundle was increased from 88%(20859/23562) to 98%(107436/109629)from the baseline survey period to July , and the overall correct implementation rate was maintained at about 98 % from July to October. Conclusion The management model based on the cluster monitoring of the key indexes of digital ICU can help to improve and improve the medical quality of ICU effectively and continuously, which is beneficial to the management of medical quality in ICU.
8.Analgesia in intensive care unit: something truly counts
Wenzhe LI ; Pengfei PAN ; Yi WANG ; Xiangyou YU
Chinese Critical Care Medicine 2019;31(1):29-33
Critical patients in the intensive care unit (ICU) are often accompanied with acute pain,which may lead to a series of physiological responses that affect the prognosis of patients.With the continuous advancement of modem medicine,the pain management strategies and analgesics have also greatly developed,and the concept has been continuously updated.In the individualized diagnosis and treatment mode,the pain management is an indispensable component of ICU comprehensive treatment.Multimodal analgesia (MMA) strategies have also shown to be effective in optimizing analgesia in critical patients.However,there are still many shortcomings and differences in pain evaluation and its management.The characteristics and methodologies of related analgesics need to be further summarized and discussed.The current literature about the evaluation of pain,pharmacology and non-pharmacological techniques were reviewed to provide references for the scientific and reasonable implementation of analgesia treatment in ICU.
9.Research progress of sepsis-associated acute kidney injury based on Gut-Kidney axis
Li ZHANG ; Yi WANG ; Xiangyou YU
Chinese Critical Care Medicine 2023;35(3):329-333
Sepsis-associated acute kidney injury (SA-AKI), as a common renal dysfunction in sepsis, has become one of the major diseases threatening human health with increasing morbidity and mortality. Based on the theory of "gut-kidney axis", the intestine and kidney have a two-way synergistic relationship in sepsis. Intestinal flora imbalance, endogenous metabolite imbalance, and impaired endothelial barrier integrity are involved in renal injury, and the increase of renal inflammatory mediators interferes with the composition of intestinal microorganisms. Therefore, understanding the intestinal-renal crosstalk mechanism of SA-AKI will help to provide a potential basis for new treatment strategies for SA-AKI.
10.Methylene blue in the treatment of vasodilatory shock: a Meta-analysis
Xiongfeng ZHANG ; Yun GAO ; Pengfei PAN ; Yi WANG ; Wenzhe LI ; Xiangyou YU
Chinese Critical Care Medicine 2017;29(11):982-987
Objective To investigate the clinical efficacy of methylene blue in the treatment of refractory hypotension caused by vascular paralysis during the course of vasodilatory shock. Methods The related articles were searched by retrieving the terms using methylene blue, vascular paralysis, hemodynamics, hypotension, vasodilatory shock in CNKI, China Biomedical Literature database, Wanfang database, PubMed, Springer Link, and BIOSIS Previews database. The retrieval time was from January 1994 to June 2017. The randomized clinical trials (RCTs) which using methylene blue as the experimental group, normal saline or catecholamine as the control in the treatment of refractory hypotension caused by vascular paralysis during the course of vasodilatory shock were collected. The primary end points were mean arterial pressure (MAP) immediately or 1 hour after the methylene blue administration, and the mortality at the longest follow-up available; the secondary end point was serum lactic acid (Lac) 1 hour after the methylene blue administration. Literature screening, data extraction and quality evaluation were carried out by two researchers. Meta analysis was performed using RevMan 5.3 software. The sensitivity analysis was performed in two trials with low risk of bias. The funnel plot for MAP was performed in five relative trials to analyze the research and publication bias. Results Totally 269 relative articles were collected, according to the inclusion and exclusion criteria, finally 6 RCTs with 214 patients were enrolled, 108 in methylene blue group, and 106 in control group. Four of the studies were considered to have mild to moderate risk of bias, two studies of high risk of bias. The Meta-analysis demonstrated that compared with the control group, methylene blue could significantly improve MAP [mean difference (MD) = 4.87, 95% confidence interval (95%CI) = 2.61 to 7.13, P < 0.000 1], reduce the serum Lac levels (MD = -1.06, 95%CI = -1.98 to -0.14, P = 0.02), and the mortality was decreased without statistical difference [odds ratio (OR) = 0.58, 95%CI = 0.25 to 1.31, P = 0.19]. Sensitivity analysis was performed in two trials with low risk of bias, which demonstrated methylene blue could exactly increase MAP (MD = 8.93, 95%CI = 1.55 to 16.32, P = 0.02). Funnel plot for MAP was performed in five relative trials which found no obvious publication bias. Conclusions Methylene blue could significantly increase MAP in the patients with refractory hypotension caused by vascular paralysis during the course of vasodilatory shock, decrease the Lac levels, and does not increase the risk of death. Therefore, methylene blue should be a potential and safe vasoconstrictor.