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Objective:To evaluate the early diagnostic value of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) in acute kidney injury induced by sepsis.Methods:A total of 85 sepsis patients admitted to the EICU and GICU in Shanghai East Hospital from September 2017 to June 2019 were divided into theAKI group ( n=37) and the non-AKI group ( n=48) according to KIDGO diagnostic criteria, and 20 healthy volunteers were served as the control group. The clinical data were recorded and samples of urine were collected at 0 h, 6 h, 12 h, 1 d, 3 d and 7 d post sepsis. The levels of TIMP-2 and IGFBP-7 in the urine were analyzed with ELISA at different time points. Based on the receiver operating characteristic curve (ROC) and the area under the curve (AUC), the early diagnostic value of urinary TIMP-2 and IGFBP-7 in sepsis-induced AKI patients was determined. Results:Compared with the control group, the levels of TIMP-2 and IGFBP-7 of the AKI group were significantly higher at the above time points ( P<0.05), while those of the non-AKI group showed no significant differences. The levels of TIMP-2 and IGFBP-7 of the AKI group were significantly higher than the those of the non-AKI group ( P<0.05). ROC analysis showed that when the AUC of urine TIMP-2 peaked at 1 d, the sensitivity and specificity reached 97.5% and 81.2%, separately with the cutoff value of 151.23 ng/mL. Furthermore, when the AUC of urine IGFBP-7 peaked at 12 h, the sensitivity and specificity reached 100% and 72.8%, separately with the cutoff value of 14.91 ng/mL. Interestingly, when the AUC of combined TIMP-2×IGFBP-7 peaked at 12 h, the sensitivity reached 98.0% and specificity reached 91.5% with the cutoff value of 2.09 [(ng/mL) 2/1 000]. There was no significant correlation between the levels of TIMP-2 and IGFBP-7 with SOFA and APACHEⅡ score at 1 d, 3 d and 7 d post sepsis in the AKI group ( P>0.05). Conclusions:Urine TIMP-2 and IGFBP-7 have early diagnostic value in sepsis-induced AKI. Besides, the combination of the two biomarkers have superior predictive value than each single of them.
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Objective To study the superiority of severe multiple trauma treatment model based on damage control strategy. Methods In the intergrated injury first-aid mode, the intensive care unit-guided damage control strategy was used to treat severe multiple trauma. Results A total of 789 severe multiple damage patients were treated with damage control strategies in our hospital from December 2018 to December 2018. Sixty-nine patients died and the survival rate was 91.25％. Conclusions The intensive care unit-guided trauma control strategy has a satisfactory clinical effect in the treatment of patients with severe multiple trauma.
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Objective To examine the expression profile of programmed death-ligand 1 (PD-L1) on lung endothelial or epithelial cells,and to determine the specific role of PD-L1 in mouse model of indirect acute lung injury (i-ALI).Methods Eighty male C57BL/6 mice were randomly divided into two parts (both n =40).The effects of different administration routes on the expression of PD-L1 were observed.The mice in each part were randomly divided into sham,i-ALI,i-ALI+small interfering RNA (siRNA) random sequence control,and i-ALI+PD-L1 siRNA which could specifically inhibit PD-L1 expression groups,with l0 mice in each group.i-ALI was reproduced in a mouse model of hemorrhagic shock in combination with a subsequent cecal ligation and puncture (CLP).In sham group,only bilateral femoral arteries were ligated without catheterization or bleeding,and only cecum was separated but perforation was not ligated.Intravenous or intratracheal delivery of PD-L1 siRNA was performed 2 hours following the resuscitation to suppress the expression of PD-L1 on lung endothelial or epithelial cells.The mice in i-ALI+siRNA random sequence control group were given siRNA random sequence without inhibition effect on PD-L1 expression,and those in sham group and i-ALI group were given 100 μL phosphate buffered saline (PBS).The mice were sacrificed at 24 hours after CLP,and samples of blood,lung tissue and bronchoalveolar lavage fluid (BALF) were harvested.Expressions of PD-L1 were determined with flow cytometry.Cytokines and chemokines in plasma,lung tissue and BALF were determined by enzyme linked immunosorbent assay (ELISA).The protein concentration in plasma and BALF and the activity of myeloperoxidase (MPO) in lung tissue were quantitatively measured.The pathological changes in lung tissue were observed under light microscope.Results ① Compared with sham group,PD-L1 expression on lung endothelial or epithelial cells were significantly elevated in i-ALI group [endothelial cells:(27.88 ± 1.53)％ vs.(19.64 ± 1.03)％,epithelial cells:(58.70 ± 8.21)％ vs.(29.23 ± 3.94)％,both P ＜ 0.05].② Mice received intravenous delivery of liposomal-encapsulated siRNA had significantly lower expression of PD-L1 on lung endothelial cells as compared with that of i-ALI group [(21.37 ± 0.76)％ vs.(27.88 ± 1.53)％,P ＜ 0.05].Intratracheal delivery of naked PD-L1 siRNA mainly inhibited the PD-L1 expression on epithelial cell as compared with that of i-ALI group [(31.23±4.71) ％ vs.(58.70±8.21) ％,P ＜ 0.05].The expression of PD-L1 in pulmonary microvascular endothelial cells or pulmonary epithelial cells of i-ALI mice was not affected by siRNA random sequence.③ PD-L1 silencing on pulmonary endothelial cells induced by intravenous delivery of PD-L1 siRNA led to a lower protein ratio of BALF/plasma [(4.48 ± 0.35) × 10-3 vs.(6.11 ± 0.56) × 10-3,P ＜ 0.05] and a decreased MPO activity in lung tissue (U · μg-1 · min-1:2.48 ± 0.47 vs.4.56 ± 0.52,P ＜ 0.05) as compared with that of i-ALI group.Moreover,inflammatory mediator levels such as interleukin-6 (IL-6),monocyte chemoattractant protein-1 (MCP-1),macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) in lung tissue or plasma were significantly reduced following PD-L1 suppression on endothelial cells as compared with those of i-ALI group [IL-6 (ng/g):177.4±23.2 vs.287.9±57.3,MCP-1 (ng/g):839.6±91.7 vs.1 395.7±211.9,MIP-2 (ng/g):923.7± 107.3 vs.1 700.9±240.2 in lung tissue;IL-6 (ng/L):950.2±192.7 vs.1 828.2±243.6,TNF-α (ng/L):258.7±29.1 vs.443.0 ± 58.1,MCP-1 (ng/L):2 583.8±302.3 vs.4 328.1 ±416.4,MIP-2 (ng/L):1 512.9± 165.6 vs.2 005.9 ± 85.7 in plasma,all P ＜ 0.05],however,there was no significant change in the levels of inflammatory factors in BALF.It was shown in lung tissue histology that PD-L1 silencing on pulmonary endothelial cells induced by intravenous delivery of PD-L1 siRNA led to lessened pulmonary edema and reduced immune cells emigration.Intratracheal delivery of PD-L1 siRNA for PD-L1 suppression on epithelial cells had minimal effects on protein ratio of BALF/plasma,MPO activity,inflammatory mediator expressions in lung tissue,plasma,and BALF as well as lung tissue histology.Conclusion PD-L1 silencing on endothelial cells but not epithelial cells protected mice against hemorrhagic shock-sepsis induced i-ALI.
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Objective: To evaluate the effects on the apical sealing ability of iRoot SP used for straight root canals. Methods: 73 extracted human teeth with straight roots were randomly assigned to 8 groups. The root canals in groups A3 was obturated with single gutta-percha cone. The others were obturated with thermoplasticized gutta-percha cones. The canals were filled with AH Plus (group A1 and B1), iRoot SP (group A2, A3 and B2) and ZOE (group A4) . The post space was prepared either immediately after obturation (A1-A4) or 7 days later group (B1 and B2) . The extent of dye penetration was measured by transparent dental technology. Results:There were no significant differences among A1-A3 groups, between group A1 and B1, A2 and B2, P＞ 0. 05. The dye penetration extent of group A4 and C was greater than that of group A2 (P ＜ 0. 05) . Conclusion: iRoot SP and AH Plus have same performance on root canal seal. There was no significant difference between iRoot SP + thermoplasticized gutta-percha and iRoot SP + single gutta-percha cone for apical sealing.
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Objective To evaluate the prognostic value of human antibacterial peptide LL-37 in elderly patients with sepsis. Methods Elderly sepsis patients over 65-year-old satisfied the diagnostic criteria for sepsis and septic shock admitted to intensive care unit of East Hospital of Tongji University from January 2016 to December 2017 were enrolled (elderly sepsis group). Aged community-acquired pneumonia (CAP) patients hospitalized during the same period were enrolled as a control group for pneumonia, and the aged health check-ups served as a healthy control group during the same period. The peripheral blood LL-37 levels of all patients on the 1st, 3rd, 7th day of admission and the results on the day of physical examination in the healthy control group and on the day of admission in aged CAP group were recorded. C-reactive protein (CRP), arterial blood lactate (Lac), procalcitonin (PCT) were monitored, and acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) scores were calculated based on the worst values within 24 hours. The correlation between LL-37 and various indicators was analyzed by Spearman method. According to the 28-day clinical outcome, the elderly patients with sepsis were divided into survival group and non-survival group. The differences in all parameters between the two groups were compared. The statistically significant indicators were analyzed by receiver operating characteristic (ROC) curve, and the predictive value of each indicator for prognosis was evaluated. Results ① A total of 113 elderly patients with sepsis were enrolled in the final analysis, including 67 patients in sepsis group and 46 patients in septic shock group. Thirty-two patients were enrolled as healthy controls and 31 elderly patients with CAP as elderly pneumonia group. The PCT, CRP, Lac, APACHEⅡ and SOFA scores of the patients in the three groups were higher than those of the healthy control group, and they were gradually increased with the severity of infection. There was no significant difference in gender or age among the groups. Compared with the healthy control group, the other three groups had higher LL-37 level after admission, the LL-37 levels in the sepsis group and the septic shock group were decreased with the prolongation of the hospitalization time, and they were lower than the pneumonia group at 7 days after admission [LL-37 (μg/L): 1 403.9±501.9, 1 517.1±676.4 vs. 1 608.4±816.2, both P > 0.05]. It was shown by correlation analysis that the LL-37 level in peripheral blood of elderly patients with sepsis was significantly negatively correlated with APACHEⅡ score (r = -0.329, P = 0.007) and SOFA score (r = -0.344, P = 0.005), but no significant correlation with Lac was found (r = -0.128, P = 0.311). ② The 28-day survival analysis revealed that of the 113 elderly patients with sepsis, 54 (47.8%) survived at 28 days and 59 (52.2%) died. There was no significant difference in gender, age, PCT or CRP levels at 1 day after admission between the two groups. The 1-day Lac, APACHEⅡ and SOFA scores of the patients in the non-survival group were significantly higher than those in the survival group, they were gradually increased with the prolongation of the hospitalization time, and they were significantly higher than those in the survival group at 7 days after admission [Lac (mmol/L): 2.4 (1.4, 4.4) vs. 1.0 (0.8, 1.7), APACHEⅡ score: 21.77±5.85 vs. 13.74±4.99, SOFA score: 9.62±4.78 vs. 3.18±2.71, all P < 0.01]. With the prolongation of admission, there was no significant change in LL-37 level of peripheral blood in the survival group. The LL-37 level in the non-survival group showed a downward tendency, and it was significantly lower than that in the survival group at 7 days after admission (μg/L: 1 277.8±642.6 vs. 1 620.6±461.6, P < 0.05). It was shown by ROC curve analysis that the LL-37 in peripheral blood, Lac, APACHEⅡ score and SOFA score at 7-day of admission of elderly patients with sepsis had predictive value for prognosis, and LL-37 had the best predicted effect for 28-day death, the area under the ROC curve (AUC) of LL-37 was 0.670, 95% confidence interval (95%CI) = 0.513-0.757, when the optimal cut-off value was 1 283.0 μg/L, the sensitivity was 75.7%, and the specificity was 61.5%. Conclusions The expression of LL-37 increased in the early course of the disease in elderly patients with sepsis. However, as the disease progressed and worsened, the level of LL-37 had a decline tendency and was associated with death. The dynamic monitoring of LL-37 combined with APACHEⅡ and SOFA scores had clinical guidance value in predicting the prognosis of sepsis in the elderly.
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Objective To explore the predicting value of peripheral blood CD20+ CD24hi CD38hi regulatory B cells (Bregs) on the prognosis of elderly patients with sepsis.Methods A prospective study was conducted. Septic patients aged > 65 years old, compliance with diagnostic criteria for Sepsis-3, admitted to emergency and emergency intensive care unit (ICU) of Shanghai East Hospital of Tongji University from April 2016 to February 2017 were enrolled. Procalcitonin (PCT), C-reaction protein (CRP) and lactate (Lac) were routinely measured. According to the worst clinical index value within 24 hours, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and sequential organ failure assessment (SOFA) score were recorded. The concentrations of peripheral blood CD20+ CD24hi CD38hi Bregs were measured by flow cytometry at 1, 3 and 7 days after diagnosed in elderly patients. All patients with sepsis were followed up for 28 days and then divided into death group and survival group according to 28-day outcome. The difference of clinic data and Bregs were compared between the two groups. The significant different factors of elderly sepsis patients were analyzed by binary logistic regression analysis. The correlation between Bregs level and other indicators was analyzed by Spearman correlation. The receiver operating characteristic curve (ROC) was used to evaluate the prognosis value of Bregs in elderly patients with sepsis.Results Fifty-eight patients were enrolled in the study, with 38 male and 20 female; age of (79.91±7.97) years; 32 in sepsis group, 26 in septic shock group; 35 deaths, 28-day mortality rate was 60.3%. APACHE Ⅱ score and SOFA score in death group exhibited much higher than that in survival group (APACHE Ⅱ: 18.14±4.52 vs. 14.91±3.56, SOFA: 8.80±4.56 vs. 6.35±3.00, bothP < 0.05), the Bregs was significantly decreased at 1, 3 and 7 days in death group [cells/μL: 0.70 (0.20, 1.40) vs. 1.50 (0.70, 2.20), 0.54 (0.20, 1.00) vs. 1.42 (1.10, 2.12), 0.25 (0.10, 0.50) vs. 0.80 (0.50, 1.00), allP < 0.05]. Correlation analysis showed that the concentrations of peripheral blood Bregs at 1 day in elderly patients with sepsis was negatively correlated with APACHE Ⅱ score (r = -0.351,P = 0.007), and it was not correlated with PCT, CRP, Lac or SOFA score. It was shown by binary logistic regression that Bregs [odds ratio (OR) = 1.865,P = 0.028] and APACHE Ⅱ score (OR = 0.853,P = 0.026) were independent risk factors for elderly sepsis outcome. It was shown by ROC curve analysis that the prognostic value of the levels of Bregs at 1, 3, 7 days and APACHE Ⅱ score were higher in the elderly patients with sepsis, and the area under ROC curve (AUC) and 95% confidence interval (95%CI) were 0.842 (0.647-0.954), 0.770 (0.564-0.911), 0.888 (0.703-0.977), 0.855 (0.661-0.961), respectively, allP < 0.01. The 7-day Bregs was most powerful to predict outcome, when the cut-off value was 0.50 cells/μL, the sensitivity was 72.73% and specificity was 86.67%. Conclusions The level of peripheral blood CD20+ CD24hi CD38hi Bregs could predict the clinical outcome of elderly patients with sepsis.
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Objective To investigate the regulatory role of programmed death ligand-1 (PD-L1) on acute lung injury (ALI), and its molecular mechanism. Methods Twenty C57BL/6 male mice and 20 PD-L1 knock out male mice were collected, and they were divided into two groups by random number table, respectively: namely sham group and ALI group, 10 mice in each group. The model of ALI was reproduced by two-hit of hemorrhagic shock and sepsis, and the mice in sham group were only got bilateral femoral artery exposure and ligation without bleeding, cecal separation without ligation and perforation. The mice were sacrificed 24 hours after model reproduction, and the lung tissue and bronchoalveolar lavage fluid (BALF) were collected. The mRNA and protein expression levels of PD-L1 in the lungs were determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western Blot. The pathological changes were observed with microscopy. The protein levels in BALF were determined. The granulocyte differentiation antigen 1 (Gr1) positive cells was determined by cytometry, and myeloperoxidase (MPO) activity in lung tissue was determined. The levels of proinflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and chemotatic factors keratinocyte chemoattractant (KC), macrophage inflammatory protein-2 (MIP-2) in lung homogenates and BALF were determined by enzyme-linked immunosorbent assay (ELISA). Results Compared with sham group, the mRNA and protein levels of PD-L1 in lung tissue of C57BL/6 mice in ALI group were significantly elevated [PD-L1 mRNA (2-ΔΔCt): 3.20±0.76 vs. 1.01±0.03, PD-L1 protein (A value): 0.98±0.16 vs. 0.15±0.04, both P < 0.05]. It was shown by light microscopy that the alveolar wall was thickened, congestive, edema and spot bleeding with a large number of inflammatory cell infiltration in the lung tissue of C57BL/6 mice in ALI group, and an obvious protein leakage was found in BALF (ng/L: 0.18±0.06 vs. 0.05±0.01, P < 0.05). The lung injury degree of PD-L1 knockout ALI mice was significantly less than that of C57BL/6 ALI mice, and the protein leakage was significantly reduced in BALF (ng/L: 0.11±0.02 vs. 0.18±0.06, P < 0.05). Compared with corresponding sham group, the number of Gr1 positive cells, MPO activity in lung tissue as well as the levels proinflammatory factors and chemotatic factors in lung tissue and BALF in ALI group were significantly increased. However, when compared with C57BL/6 ALI mice, above parameters in lung homogenates and BALF were significantly decreased in PD-L1 knockout ALI mice [number of Gr1 positive cells: (39.0±4.0)% vs. (45.0±8.0)%, MPO activity (U·μg-1·min-1): 2.85±0.62 vs. 4.52±1.16; lung IL-6 (ng/g): 461±111 vs. 728±28, TNF-α (ng/g): 1 123±175 vs. 1 500±327, KC (ng/g): 150±34 vs. 250±28, MIP-2 (ng/g): 1 263±468 vs. 1 763±323; BALF IL-6 (ng/L): 134±22 vs. 258±38, TNF-α (ng/L): 598±102 vs. 889±139, KC (ng/L): 934±286 vs. 1 258±336, MIP-2 (ng/L): 650±130 vs. 950±256; all P < 0.05]. Conclusion PD-L1 may play an important protective role in the immunological mechanism of ALI, which may be mediated by decreasing chemotactic factor KC and MIP-2 and mitigating neutrophil chemotaxis in lung tissue.
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Objective:To observe the effects of Dyad Flow self-adhering flowable composite in the minimal invasive treatment of decid-uous molar caries.Methods:31 7 deciduous molars caries of 206 patients were randomly divided into 3 groups and treated by minimal invasive method,the cavities of the molars were filled with Dyad Flow self-adhering flowable composite(group A,n =1 07),traditional flowable composite and self-etching adhesive(group B,n =1 04)and glass ion(group C,n =1 06)respectively.The children were fol-lowed up for 1 and 2 years after treatment.Results:1 year after treatment the success rate(%)of group A,B and C was 95.3,96.77 and 91 .84(P >0.05);2 years after treatment 89.1 9,90.67 and 79.45(P >0.05),respectively.Conclusion:Dyad Flow self-adhe-ring flowable composite is effective in the treatment of deciduous molar caries.
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AIM: To detect the expression of IL-13 and TGF-? during airway remodeling. METHODS: A airway remodeling model was established and histological changes were detected under light or electronic microscope. In situ hybridization assays were adopted to determine the status of IL-13 and TGF-?_2 transcript in lung tissue and Western blot was used to detect the expression of p38MAPK protein. RESULTS: Proliferation of airway epithelium and smooth muscle and mucous plugs were found in lung tissue of airway remodeling mice , accompanied by infiltration of eosinophils and lymphocytes in airway. Overexpression of IL-13,TGF-?_2 mRNA and p38MAPK were also observed in airway remodeling group. CONCLUSION: Expression of IL-13, TGF-?_2 mRNA and p38MAPK protein increased significantly during airway remodeling, which may suggest an role for Th2 cytokines, TGF-?_2 in the pathogenesis of airway remodeling. p38 MAPK may be associated with the development of asthma and airway remodeling. [