Naringenin protects ischemia-reperfusion-induced acute kidney injury by nuclear factor κB / 中华肾脏病杂志

Objective:To explore the effect and involved mechanism of naringenin on acute kidney injury (AKI) induced by ischemia-reperfusion (IR).Methods:The IR-AKI rat model was constructed using the classic bilateral renal pedicle clamping method, then renal function and pathological change were assessed, as well as inflammation-associated genes were detected by quantitative real-time PCR. The hub genes were selected through differential gene analysis and protein-protein interaction network analysis, and their transcription factors were predicted, which constructed a protein library together. The proteins binding to naringenin were selected by reverse molecular docking analysis and further their binding patterns were predicted to explore the mechanism of naringenin. Finally, the results of bioinformatics were verified by experimental methods.Results:Compared with the AKI group, the kidney pathology of the rats in the naringenin pretreatment group was significantly improved, and the renal tubular injury score was reduced ( P<0.01); meanwhile the serum creatinine level and the mRNA expression of the kidney injury molecule 1 (KIM-1) were significantly decreased (both P<0.05). Compared to sham group, IR-AKI increased the level of nuclear factor κB (NF-κB), tumor necrosis factor-α and interleukin-1β (all P<0.05), which reversed by naringenin indicated that naringenin inhibited inflammation in IR-AKI. Differential gene analysis was performed on the GSE98622 data set, and 359 differential genes were obtained. In reverse molecular docking, the proteins with smallest binding energy including NFKBIA, BCL3, NFKB2 and RELA were considered to be related to the preventive effect of naringenin, which were mainly enriched in NF-κB-related inflammation pathways. Domain functional analysis of NF-κB-related genes showed that naringenin could stably bind to its key domain. According to quantitative real-time PCR results, naringenin increased BCL3 level after AKI ( P<0.05), and further decreased the expression level of RELA and NFKB2 (both P<0.05). Conclusion:Naringenin protects IR-AKI by alleviating inflammation, and its mechanism is related to increasing BCL3 and thereby inhibiting the NF-κB pathway.

Risk factors of acute kidney injury in hospitalized patients with infective endocarditis and their predictive values / 中华危重病急救医学

Objective:To analyze the risk factors of acute kidney injury (AKI) in hospitalized patients with infective endocarditis (IE), construct prediction model, and discuss its predictive value.Methods:The clinical data of 402 adult inpatients diagnosed with IE admitted to the Affiliated Hospital of Qingdao University from January 2010 to January 2020 were retrospectively analyzed. The patients were divided into the AKI group and the non-AKI group. The clinical data, such as gender, age, presence of diabetes, basic estimated glomerular filtration rate (eGFR), laboratory indexes at admission, involvement of valves, presence of sepsis, medication during hospitalization, surgery and outcome of the two groups were compared. Multivariate Logistic regression analysis was used to screen the risk factors of AKI in IE inpatients. A predictive model was constructed, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of the model.Results:A total of 290 patients with IE were enrolled, including 198 non-AKI patients and 92 AKI patients. The incidence of AKI was 31.7%. Among the 92 AKI patients, 46 patients were at AKI stage 1 (50.0%), while 46 patients were at AKI stage 2 and stage 3 (50.0%). Compared with the non-AKI group, patients in the AKI group were older [years old: 64 (55, 71) vs. 55 (46, 63)], and had lower basic eGFR (mL·min -1·1.73 m -2: 64.6±13.6 vs. 82.9±19.5), higher proportion of diabetic and incidence of sepsis (16.3% vs. 8.6%, 38.0% vs. 13.1%), more frequent use of angiotensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists (ACEI/ARB), diuretics and non-steroidal anti-inflammatory drugs (NSAIDs; 25.0% vs. 15.2%, 82.6% vs. 63.1%, 58.7% vs. 24.2%), more abnormal urine test results (hematuria or proteinuria, 35.9% vs. 22.7%), higher pathogen culture negative rate (73.9% vs. 51.5%), lower Gram positive (G +) cocci infection rate and surgery rate (22.8% vs. 40.4%, 60.9% vs. 81.8 %), with significant differences (all P < 0.05). There were no significant differences in the gender, number and location of involved valves, and laboratory indexes at admission between the two groups. Compared with the non-AKI group, the inpatient mortality rate of the AKI group was higher (30.4% vs. 8.6%, P < 0.01), and the inpatient mortality rate of patients with AKI stage 2 and stage 3 was significantly higher than that of patients with AKI stage 1 (43.5% vs. 17.4%, P < 0.01). In multivariate Logistic regression analysis, the lower basic eGFR [hazard ratio ( HR) = 0.136, 95% confidence interval (95% CI) was 0.066-0.280], sepsis ( HR = 6.100, 95% CI was 2.394-15.543), demand for NSAIDs ( HR = 2.990, 95% CI was 1.184-7.546) and radiocontrast agent ( HR = 3.153, 95% CI was 1.207-8.238) were independent risk factors for AKI in hospitalized patients with IE (all P < 0.05). A prediction model was constructed based on the above risk factors, and ROC curve analysis showed that the area under the ROC curve (AUC) of prediction model for AKI was 0.888 (95% CI was 0.833-0.943, P < 0.01) with sensitivity of 86.4% and specificity of 80.9%. Conclusions:In the IE-susceptible population, low basic eGFR, sepsis, the need for NSAIDs and contrast agent are independent risk factors to AKI. The predictive model constructed by the above risk factors has certain predictive value for the occurrence of AKI in the IE inpatients.

Clinical value of gas partial pressure evaluation to the closure of visceral pleura in pneumothroax patients / 天津医药

Objective To study the predictive value of evaluation in oxygen partial pressure[p(O2)] and carbon dioxide partial pressure[p(CO2)] of pleural cavity to the closure of visceral pleura in primary spontaneous pneumothroax (PSP) pa-tients. Methods Seventy-six hospitalized pneumothroax patients were divided into two groups:closed pneumothroax group (n=40) and open pneumothroax group (n=36), according to the radiographic information.To collect the expiratory gas by the device which we designed and produced, to collect the gas in the pleural cavity by thoracentesis. To detect the p(O2)and p(CO2)respectively, and the blood gas analysis of radial artery was done at same time. Results There was significantly low-er value of p(O2)of the gas in the pleural cavity in patients of closed pneumothroax than that of open pneumothroax (P 0.05). There was significantly higher value of the expiratory gas/the pleural cavity gas p(O2) and a significantly lower value of p(CO2), in closed pneumothroax group than those of open pneumothroax group (P<0.05). Logistic regression analy-sis showed that values of the expiratory gas/the pleural cavity gas p(O2) and p(CO2) were the effective factors for the closure of visceral pleura. ROC curve showed that the areas under ROC curve (AUC) for the expiratory gas/the pleural cavity gas p(O2) and p(CO2) was 0.985 and 0.867, the sensitivities were 92.5% and 77.8%, the specificities were 100%and 85.0%and the reference values were 1.81 and 0.97. Conclusion To utilize the evaluation of gas partial pressure can predict whether the leakage of the visceral pleura is closed.

Effect of closed chest drain on wound closure of primary spontaneous pneumothorax / 天津医药

Objective To explore the relationship between visceral pleura closure of primary spontaneous pneumotho?rax (PSP) using different diameters of drainage tube and the time of implementing closed chest-drain. Methods According to the diameters of tubes for chest drain they used, 214 patients with PSP were divided into standard tube group (136 cases) and fine catheter group (78 cases). Patients in standard tube group who were inserted chest drain for≤1 d,≤3 d,≤6 d,>6 d included 48, 43, 29 and 16 cases respectively while their counterpart in fine catheter group include 24, 23, 17, 14 cases re?spectively. Closed time of crevasse were noted and incidence of preoperative closed pneumothorax converting into open pneu?mothorax, subcutaneous emphysema and prolonged pain after operation were all recorded. Results There is no statistical difference in closing time of crevasse nor in the distribution of various drainage times (proportions of≤6 d and>6 d are low?er than proportions of≤1 d and≤3 d) between standard tube group [(4.76 ±1.65) d] and fine catheter group [(4.54±1.67) d] (t=0.963). However, in both standard tube group and fine catheter group, closing time of crevasse is shorter if drainage time≤6 d or>6 d than if it≤1 d and≤3 d. Closing time of crevasse show negative correlation with period of chest drain in?sertion in both standard tube group and fine catheter group (P<0.05). The rate of converting from close pneumothorax into open pneumothorax were 51.96%(53/102) and 36.21%(21/58) respectively in standard pipe group and fine catheter group. Furthermore, the incidence of subcutaneous emphysema and prolonged pain were all higher than those in standard tube group than those in the fine catheter group (P<0.05). Conclusion Using closed chest drain to treat patients with PSP, di?ameter of the drain tube did not affect closing time of crevasse. But longer insertion period of chest drain can reduce closing time of crevasse.

Guiding values of different lung compressed forms in spontaneous pneumothorax on the choice of the treatment / 天津医药

Objective To evaluate the guiding values of different lung compressed forms in the choice of the treat?ment of spontaneous pneumothorax. Methods Based on lung compressed forms on anterior-posterior chest X-ray , a total of 219 spontaneous pneumothorax patients were divided into the periphery shape group (n=127) and irregular shape group (n=92). We observe the relationship between lung compressed form with the times of previous closed thoracic drainage,the cure rate of closed chest drain at the 7th day,length that closed thoracic drainage cure pneumothorax and the incidences of the surgical pleural adhesion. Results We found that the incidence of irregular lung compression in 0, 1 and 2 times of re?ceiving previous drainage were 11.71%(13/111), 57.89%(22/57) and 90.19%(46/51) respectively. Its incidence increased with the times of previous closed chest drain (χ2=96.339, P<0.01). In total, 94 patients (85 of which were cured until the 7th day) and 30 patients (11 of which were cured until the 7th day) were cured using close chest drain in peripheral shape and ir?regular shape group. And the 7th day cure rate is lower in irregular group than that in the peripheral shape. [36.7%(11/30) vs 90.4%(85/94),χ2=37.596, P<0.01]. What’s more, patients in irregular group need longer time to cure pneumothorax than patients in peripheral shape did [d:10.1±4.87 vs 4.00±2.07, t=9.806, P<0.01]. Among the 95 patients who underwent surgi?cal treatment in both groups, the incidence of pleural adhesion is higher in irregular shape group than that in peripheral shape group [91.9%(57/62)vs18.2%(6/33),χ2=52.445, P<0.01]. Conclusion The 7th day cure rate in patients with pe?ripheral shape lung compressed form is higher than patients in irregular lung compressed form using closed chest drain with fewer incidence of pleural adhesion and shorter cure time. Those with irregular lung compression is more appropriate for sur?gical treatment.

Joint effects of hydroxyethyl starch and furosemide on acute lung injury induced by paraquat in swine / 中华急诊医学杂志

Objective To discuss the jointly therapeutic effects of 6％ hydroxyethyl starch 130/0.4 (voluven) and furosemide on acute lung injury induced by paraquat (PQ) in swine.Methods The ALI/ ARDS models were established with 20％ PQ (20 mL) intraperitoneal injection in 18 healthy female piglets and randomly divided into three groups: voluven group (A), furosemide group (B) and voluven + furosemide group (C) (n =6 in each group).The heart rate (HR), mean arterial pressure (MAP), extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), partial pressure of carbon dioxide (PaCO2) and oxygenation index (PaO2/FiO2) among the three groups were carefully measured by PICCO (pulse indicator continuous cardiac output) before modeling (baseline), just aftermodeling (t0), and 2 h (t2), 4 h (t4), 6 h (t6) and 8 h (t8) after trearment.Needle biopsies of lung tissue were made before modeling and at t0 and t8 and prepared for microscopy observation after Hematoxylineosin staining method (HE staning).Repeated measurement data were compared among repeated measures by the ANOVA and the difference between groups was compared by one-wey ANOVA.Results (1) The HR and MAP of all animals increased obviously while the oxygenation index declined significantly at modeling just made (t0) compared to those before modeling (all P ＜ 0.05).At the same time, the HR and MAP of A and B groups were significantly lower than those of C group after treatment (all P ＜ 0.05), while the oxygenation index of A and B were significantly higher (all P ＞ 0.05).(2) The ELWI and PVPI of all animals increased obviously at modeling just made (t0) compared to those before modeling (all P ＜ 0.05).The ELWI and PVPI were decreased after treatment.And at the same time, the ELWI and PVPI of A and B groups were significantly lower than those of C group after treatment (all P ＜ 0.05).(3) The alveolar tissue showed obviously injured changes at modeling just made (t0).The injury was relieved 8h after trearment, which was most markedly in group C.Conclusions With the combination of 6％ hydroxyethyl starch 130/0.4 and furosemide administered, the acute lung injury induced by paraquat poisoning can be effectively relieved, promoting gas exchange, and improve oxygenation.

Observation on the best dose of methylprednisolone improving lung injury in swine with paraquat intoxication / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the best dose of methylprednisolone improving lung injury in swine with paraquat intoxication.</p><p><b>METHODS</b>Acute lung injury (ALI/ARDS) model was made by an intraperitoneal injection of a large dose of 20%PQ solution20 millilitres in swine. Then 24 swine were randomly divided into 4 groups: exposed PQ control group, 5 mg/kg of methylprednisolone group, 15 mg/kg of methylprednisolone group, 30 mg/kg of methylprednisolone group. All groups were based on the conventional rehydration for intervention, Arterial blood samples were collected before modeling and 0, 12, 24, 36 hours after different processing for blood gas analysis. At the same time heart rate (HR), mean arterial pressure (MAP), extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were measured by using PICCO (pulse indicator continuous cardiac output), lung tissue was obtained by punctureneedle to produce lung biopsy, then observe the pathological changes of lung tissue in the microscope.</p><p><b>RESULTS</b>1. Comparison between groups: there is no significant difference about extravascular lung water index (EVLWI) and semi-quantitative score of lung tissue pathology in four groups (P > 0.05) before modeling, so is t0, there is significant difference at about extravascular lung water index and semi-quantitative score of lung tissue pathology 12 h, 24 h and 36 h after different processing (P < 0.05). Within the group: EVLWI and semi-quantitative score of Lung tissue pathology in four groups significantly increased when the model was made (P < 0.05), after different processing, EVLWI and semi-quantitative score of Lung tissue pathology in exposed PQ control group kept going up, in other three groups, EVLWI and semi-quantitative score of lung tissue pathology went down first and then went up, there is significant difference compared with t0 (P < 0.05). 2. Comparison between groups: there is no significant difference about oxygenation index in four groups (P > 0.05) before modeling, so is t0, there is significant difference about oxygenation at 12 h, 24 h and 36 h after different processing (P < 0.05). Within the group: oxygenation index in four groups significantly decreased when the model was made (P < 0.05), after different processing, oxygenation index in exposed PQ control group kept going down, in other three groups, it showed a downward trend after the first rise, there is significant difference compared with t0 (P < 0.05). 3. After medication for 36h, correlation analysis showed that EVLWI were negatively associated with oxygenation index (r = -0.427, P = 0.022) and positively associated with semi-quantitative score of Lung tissue pathology (r = 0.903, P = 0.034).</p><p><b>CONCLUSION</b>Methylprednisolone can obviously relieve lung injury caused by paraquat poisoning and improve oxygenation. After the model was made, within 24 hours, 30 mg/kg of methylprednisolone have advantage for the PQ poisoning swine, but 15mg/kg of methylprednisolone is best for improving lung injury induced by paraquat intoxication within 24 hours to 36 hours.</p>

The significance of serum peptidylarginine deiminase type 4 in ANCA-associated vasculitis / 中华肾脏病杂志

Objective To explore the significance of peptidylarginine deiminase type 4 (PAD4) in the pathogenesis of ANCA-associated vasculitis (AAV) by detecting its level in patients with AAV.Methods Sera from 13 patients with AAV,11 patients with primary chronic kidney disease and 12 healthy controls were collected.Serum PAD4 was detected using commercial ELISA kits.The association between serum PAD4 and BVAS of AAV was further investigated.Results (1) The serum level of PAD4 in patients with AAV in active and remission stages were all higher than that in the healthy controls.The serum level of PAD4 in patients with CKD was not found elevated compared with the normal controls.(2) The serum levels of PAD4 in AAV with renal damage were all significantly higher than that in CKD group no matter in active or remission stage.(3) The serum level of PAD4 in AAV with renal damage in active stage was positively correlated with BVAS (r=0.71,P=0.02).Conclusion PAD4 is involved in the pathogenesis of AAV.

Analysis on Drug Combination Rule in Mutual Restraint Based on Apriori and Clustering Algorithm / 中国中医药信息杂志

Objective To investigate the drug combination of mutual restraint which is one of the application of seven different combination in drug in traditional Chinese medicine. Methods With the methods of association rules and complex system entropy clustering, we analyzed the drug combinations of mutual restraint that were collected from Compendium of Material Medica, to obtain the frequence of the single drug and drug combination of mutual restraint and the association rules between them. Results The single drugs with higher frequency are Rhizoma Coptidis, Fructus Crotonis, Rhei Radix Et Rhizoma, Azurite, Rhizoma Acori Tatarinowii, etc. The drug combinations with higher frequency are Azurite and Artemisia capillaries, Fructus Crotonis and Rhizoma Coptidis, Fructus Crotonis and Soybean etc. The associative drug combinations which confidence is 1 include “Indigo juice → Fructus Crotonis”,“Indigo juice → Rhizoma Coptidis”, etc. Conclusion The drug combinations of mutual restraint mainly include mineral drugs, antipyretics, purgatives, and toxic drugs.