Quick guideline for diagnosis and treatment of novel coronavirus Omicron variant infection / 中华临床感染病杂志

Novel coronavirus Omicron variant infection can cause severe illness and even death in certain populations. Omicron variant infection may lead to systemic inflammatory response, coagulation disorder, multi-organ dysfunction and other pathophysiological changes, which are different from other Novel coronavirus variants to a certain extent, so therapeutic strategies should not be the same. The National Medical Center for Major Public Health Events invited experts in fields of infectious diseases, respiratory medicine, intensive care, pediatrics and fever clinic to develop this quick guideline based on the current best evidence and extensive clinical practices. This quick guideline aims to standardize the diagnosis and treatment of novel coronavirus Omicron infection, and to improve the disease management abilities of clinicians.

Research progress in the role of glucose-regulated protein 78 in mucormycosis / 中华微生物学和免疫学杂志

Mucormycosis is an infectious disease characterized by rapidly progressive vascular invasiveness, thrombosis and tissue necrosis, which could be potentially responsible for blocking the exudation of leukocytes to infection sites and affecting drug distribution. Glucose-regulated protein 78 (GRP78) is a key protein involved in regulating the invasiveness of Mucorales. Endoplasmic reticulum GRP78 is overexpressed under various stress conditions and transported to the cell membrane to become a cell surface receptor for Mucorales entering into vascular endothelial cells. This article reviewed the mechanisms and pathogenesis of GRP78-mediated host cell invasion and summarized the progress in related targeted drugs, aiming to provide reference for developing multi-target intervention against mucormycosis.

Analysis and Prediction of False Negative Results for SARS-CoV-2 Detection with Pharyngeal Swab Specimen in COVID-19 Patients: A Retrospective Study

BackgroundFalse negative results of SARS-CoV-2 nucleic acid detection pose threats to COVID-19 patients and medical workers alike. ObjectiveTo develop multivariate models to determine clinical characteristics that contribute to false negative results of SARS-CoV-2 nucleic acid detection, and use them to predict false negative results as well as time windows for testing positive. DesignRetrospective Cohort Study (Ethics number of Tongji Hospital: No. IRBID: TJ-20200320) SettingA database of outpatients in Tongji Hospital (University Hospital) from 15 January 2020 to 19 February 2020. Patients1,324 outpatients with COVID-19 MeasurementsClinical information on CT imaging reports, blood routine tests, and clinic symptoms were collected. A multivariate logistic regression was used to explain and predict false negative testing results of SARS-CoV-2 detection. A multivariate accelerated failure model was used to analyze and predict delayed time windows for testing positive. ResultsOf the 1,324 outpatients who diagnosed of COVID-19, 633 patients tested positive in their first SARS-CoV-2 nucleic acid test (47.8%), with a mean age of 51 years (SD=14.9); the rest, which had a mean age of 47 years (SD=15.4), tested negative in the first test. "Ground glass opacity" in a CT imaging report was associated with a lower chance of false negatives (aOR, 0.56), and reduced the length of time window for testing positive by 26%. "Consolidation" was associated with a higher chance of false negatives (aOR, 1.57), and extended the length of time window for testing positive by 44%. In blood routine tests, basophils (aOR, 1.28) and eosinophils (aOR, 1.29) were associated with a higher chance of false negatives, and were found to extend the time window for testing positive by 23% and 41%, respectively. Age and gender also affected the significantly. LimitationData were generated in a large single-center study. ConclusionTesting outcome and positive window of SARS-CoV-2 detection for COVID-19 patients were associated with CT imaging results, blood routine tests, and clinical symptoms. Taking into account relevant information in CT imaging reports, blood routine tests, and clinical symptoms helped reduce a false negative testing outcome. The predictive AFT model, what we believe to be one of the first statistical models for predicting time window of SARS-CoV-2 detection, could help clinicians improve the accuracy and efficiency of the diagnosis, and hence, optimizes the timing of nucleic acid detection and alleviates the shortage of nucleic acid detection kits around the world. Primary Funding SourceNone.

Development and external validation of a prognostic multivariable model on admission for hospitalized patients with COVID-19

BackgroundCOVID-19 pandemic has developed rapidly and the ability to stratify the most vulnerable patients is vital. However, routinely used severity scoring systems are often low on diagnosis, even in non-survivors. Therefore, clinical prediction models for mortality are urgently required. MethodsWe developed and internally validated a multivariable logistic regression model to predict inpatient mortality in COVID-19 positive patients using data collected retrospectively from Tongji Hospital, Wuhan (299 patients). External validation was conducted using a retrospective cohort from Jinyintan Hospital, Wuhan (145 patients). Nine variables commonly measured in these acute settings were considered for model development, including age, biomarkers and comorbidities. Backwards stepwise selection and bootstrap resampling were used for model development and internal validation. We assessed discrimination via the C statistic, and calibration using calibration-in-the-large, calibration slopes and plots. FindingsThe final model included age, lymphocyte count, lactate dehydrogenase and SpO2 as independent predictors of mortality. Discrimination of the model was excellent in both internal (c=0{middle dot}89) and external (c=0{middle dot}98) validation. Internal calibration was excellent (calibration slope=1). External validation showed some over-prediction of risk in low-risk individuals and under-prediction of risk in high-risk individuals prior to recalibration. Recalibration of the intercept and slope led to excellent performance of the model in independent data. InterpretationCOVID-19 is a new disease and behaves differently from common critical illnesses. This study provides a new prediction model to identify patients with lethal COVID-19. Its practical reliance on commonly available parameters should improve usage of limited healthcare resources and patient survival rate. FundingThis study was supported by following funding: Key Research and Development Plan of Jiangsu Province (BE2018743 and BE2019749), National Institute for Health Research (NIHR) (PDF-2018-11-ST2-006), British Heart Foundation (BHF) (PG/16/65/32313) and Liverpool University Hospitals NHS Foundation Trust in UK. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSince the outbreak of COVID-19, there has been a pressing need for development of a prognostic tool that is easy for clinicians to use. Recently, a Lancet publication showed that in a cohort of 191 patients with COVID-19, age, SOFA score and D-dimer measurements were associated with mortality. No other publication involving prognostic factors or models has been identified to date. Added value of this studyIn our cohorts of 444 patients from two hospitals, SOFA scores were low in the majority of patients on admission. The relevance of D-dimer could not be verified, as it is not included in routine laboratory tests. In this study, we have established a multivariable clinical prediction model using a development cohort of 299 patients from one hospital. After backwards selection, four variables, including age, lymphocyte count, lactate dehydrogenase and SpO2 remained in the model to predict mortality. This has been validated internally and externally with a cohort of 145 patients from a different hospital. Discrimination of the model was excellent in both internal (c=0{middle dot}89) and external (c=0{middle dot}98) validation. Calibration plots showed excellent agreement between predicted and observed probabilities of mortality after recalibration of the model to account for underlying differences in the risk profile of the datasets. This demonstrated that the model is able to make reliable predictions in patients from different hospitals. In addition, these variables agree with pathological mechanisms and the model is easy to use in all types of clinical settings. Implication of all the available evidenceAfter further external validation in different countries the model will enable better risk stratification and more targeted management of patients with COVID-19. With the nomogram, this model that is based on readily available parameters can help clinicians to stratify COVID-19 patients on diagnosis to use limited healthcare resources effectively and improve patient outcome.

Evaluation of the clinical characteristics of suspected or confirmed cases of COVID-19 during home care with isolation: A new retrospective analysis based on O2O

BackgroundThe recent outbreak of the novel coronavirus in December 2019 (COVID-19) has activated top-level response nationwide. We developed a new treatment model based on the online-to-offline (O2O) model for the home isolated patients, because in the early stages the medical staff were insufficient to cope with so many patients. MethodsIn this single-centered, retrospective study, we enrolled 48 confirmed/suspected COVID-19 patients who underwent home isolation in Wuhan between January 6 and January 31, 2020. By WeChat and online document editing all patients were treated with medical observation scale. The clinical indications such as Fever, Muscle soreness, Dyspnea and Lack of strength were collected with this system led by medical staff in management, medicine, nursing, rehabilitation and psychology. FindingsThe mean age of 48 patients was 39{middle dot}08{+/-}13{middle dot}88 years, 35(72{middle dot}9%) were women. Compared with non-hospitalized patients, inpatients were older([≥]70years, 2{middle dot}4% vs 33{middle dot}3%, P<0{middle dot}04). All inpatients had fever, 50% inpatients had coughs and showed infiltration in both lungs at the time of diagnosis. 33{middle dot}3% inpatients exhibited negative changes in their CT results at initial diagnosis. The body temperature of non-hospitalized patients with mild symptoms returned to normal by day 4-5. While dyspnea peaked on day 6 for non-hospitalized patients with mild symptoms, it persisted in hospitalized patients and exacerbated over time. The lack of strength and muscle soreness were both back to normal by day 4 for non-hospitalized patients. InterpretationMonitoring the trends of symptoms is more important for identifying severe cases. Excessive laboratory data and physical examination are not necessary for the evaluation of patients with mild symptoms. The system we developed is the first to convert the subjective symptoms of patients into objective scores. This type of O2O, subjective-to-objective strategy may be used in regions with similar highly infectious diseases to minimize the possibility of infection among medical staff.

Clinical and immunologic features in severe and moderate forms of Coronavirus Disease 2019

BackgroundSince late December, 2019, an outbreak of pneumonia cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and continued to spread throughout China and across the globe. To date, few data on immunologic features of Coronavirus Disease 2019 (COVID-19) have been reported. MethodsIn this single-centre retrospective study, a total of 21 patients with pneumonia who were laboratory-confirmed to be infected with SARS-CoV-2 in Wuhan Tongji hospital were included from Dec 19, 2019 to Jan 27, 2020. The immunologic characteristics as well as their clinical, laboratory, radiological features were compared between 11 severe cases and 10 moderate cases. ResultsOf the 21 patients with COVID-19, only 4 (19%) had a history of exposure to the Huanan seafood market. 7 (33.3%) patients had underlying conditions. The average age of severe and moderate cases was 63.9 and 51.4 years, 10 (90.9%) severe cases and 7 (70.0%) moderate cases were male. Common clinical manifestations including fever (100%, 100%), cough (70%, 90%), fatigue (100%, 70%) and myalgia (50%, 30%) in severe cases and moderate cases. PaO2/FiO2 ratio was significantly lower in severe cases (122.9) than moderate cases (366.2). Lymphocyte counts were significantly lower in severe cases (0.7 x 10{square}/L) than moderate cases (1.1 x 10{square}/L). Alanine aminotransferase, lactate dehydrogenase levels, high-sensitivity C-reactive protein and ferritin were significantly higher in severe cases (41.4 U/L, 567.2 U/L, 135.2 mg/L and 1734.4 ug/L) than moderate cases (17.6 U/L, 234.4 U/L, 51.4 mg/L and 880.2 ug /L). IL-2R, TNF- and IL-10 concentrations on admission were significantly higher in severe cases (1202.4 pg/mL, 10.9 pg/mL and 10.9 pg/mL) than moderate cases (441.7 pg/mL, 7.5 pg/mL and 6.6 pg/mL). Absolute number of total T lymphocytes, CD4+T cells and CD8+T cells decreased in nearly all the patients, and were significantly lower in severe cases (332.5, 185.6 and 124.3 x 106/L) than moderate cases (676.5, 359.2 and 272.0 x 106/L). The expressions of IFN-{gamma} by CD4+T cells tended to be lower in severe cases (14.6%) than moderate cases (23.6%). ConclusionThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+T cells, resulting in significant decrease in number as well as IFN-{gamma} production, which may be associated with disease severity. Together with clinical characteristics, early immunologic indicators including diminished T lymphocytes and elevated cytokines may serve as potential markers for prognosis in COVID-19.

Stratified outcomes of "Kidney Disease: Improving Global Outcomes" serum creatinine criteria in critical ill patients: a secondary analysis of a multicenter prospective study / 中华危重病急救医学

Objective:To investigate the different outcomes of two types of acute kidney injury (AKI) according to standard of Kidney Disease: Improving Global Outcomes-AKI (KDIGO-AKI), and to analyze the risk factors that affect the prognosis of intensive care unit (ICU) patients in China.Methods:A secondary analysis was performed on the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a multicenter prospective study involving 3 063 patients in 22 tertiary ICUs in 19 provinces and autonomous regions of China. The demographic data, scores reflecting severity of illness, laboratory findings, intervention during ICU stay were extracted. All patients were divided into pure AKI (PAKI) and acute on chronic kidney disease (AoCKD). PAKI was defined as meeting the serum creatinine (SCr) standard of KDIGO-AKI (KDIGO-AKI SCr) and the estimated glomerular filtration rate (eGFR) at baseline was ≥ 60 mL·min -1·1.73 m -2, and AoCKD was defined as meeting the KDIGO-AKI SCr standard and baseline eGFR was 15-59 mL·min -1·1.73 m -2. All-cause mortality in ICU within 28 days was the primary outcome, while the length of ICU stay and renal replacement therapy (RRT) were the secondary outcome. The differences in baseline data and outcomes between the two groups were compared. The cumulative survival rate of ICU within 28 days was analyzed by Kaplan-Meier survival curve, and the risk factors of ICU death within 28 days were screened by Cox multivariate analysis. Results:Of the 3 063 patients, 1 042 were enrolled, 345 with AKI, 697 without AKI. The AKI incidence was 33.11%, while ICU mortality within 28 days of AKI patients was 13.91% (48/345). Compared with PAKI patients ( n = 322), AoCKD patients ( n = 23) were older [years old: 74 (59, 77) vs. 58 (41, 72)] and more critical when entering ICU [acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score: 23 (19, 27) vs. 15 (11, 22)], had worse basic renal function [eGFR (mL·min -1·1.73 m -2): 49 (38, 54) vs. 115 (94, 136)], more basic complications [Charlson comorbidity index (CCI): 3 (2, 4) vs. 0 (0, 1)] and higher SCr during ICU stay [peak SCr for diagnosis of AKI (μmol/L): 412 (280, 515) vs. 176 (124, 340), all P < 0.01]. The mortality and RRT incidence within 28 days in ICU of AoCKD patients were significantly higher than those of PAKI patients [39.13% (9/23) vs. 12.11% (39/322), 26.09% (6/23) vs. 4.04% (13/322), both P < 0.01], while no significant difference was found in the length of ICU stay. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate in ICU in AoCKD patients was significantly lower than PAKI patients (Log-Rank: χ2 = 5.939, P = 0.015). Multivariate Cox regression analysis showed that admission to ICU due to respiratory failure [hazard ratio ( HR) = 4.458, 95% confidence interval (95% CI) was 1.141-17.413, P = 0.032], vasoactive agents treatment in ICU ( HR = 5.181, 95% CI was 2.033-13.199, P = 0.001), and AoCKD ( HR = 5.377, 95% CI was 1.303-22.186, P = 0.020) were independent risk factors for ICU death within 28 days. Conclusion:Further detailed classification (PAKI, AoCKD) based on KDIGO-AKI SCr standard combined with eGFR is related to ICU mortality in critical patients within 28 days.

Diagnostic value of plasma procalcitonin for bacterial infection in patients receiving extracorporeal membrane oxygenation / 中华急诊医学杂志

Objective To evaluate the diagnostic value of plasma procalcitonin (PCT) for bacterial infection in patients receiving extracorporeal membrane oxygenation (ECMO). Methods Clinical data of patients receiving ECMO therapy admitted between August 2016 and January 2018 in Department of Critical Care Medicine, Tongji Hospital of Tongji Medical College were analyzed retrospectively. All patients receiving ECMO with bacterial culture were eligible for inclusion. Plasma PCT, IL-6, CRP and WBC levels detected within 24 h of bacterial cultures were analyzed immediately. Bacterial infection in ECMO was determined through bacterial culture and clinical characteristics. Finally, receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of inflammatory markers for bacterial infection in ECMO patients. Results Seventeen patients met the inclusion criteria, including 15 patients with acute respiratory failure and 2 patients with acute circulatory failure. There were 37 positive bacterial cultures, and 91 plasma PCT levels were detected in the process of ECMO. Compared with IL-6, CRP and WBC, plasma PCT had significant clinical significance in the diagnosis of bacterial infection (AUC=0.818, P<0.001). The cut-off value of PCT was 1.0 ng/mL, with a sensitivity of 92％ and a specificity of 43％. Conclusions Compared with other conventional inflammatory markers, plasma PCT has more diagnostic value for bacterial infection in ECMO patients.

The expression level of serum IL-7 and its influence on prognosis in patients with acute coronary syndrome / 心血管康复医学杂志

Objective: To explore the expression level of serum interleukin (IL)-7 in patients with acute coronary syndrome (ACS) and analyze the relationship between IL-7 level and prognosis. Methods: A total of 130 ACS patients [ACS group, including 70 cases with acute myocardial infarction (AMI) and 60 cases with unstable angina pectoris (UAP)], 33 cases with stable angina pectoris (SAP，SAP group) and 89 healthy subjects (healthy control group) were selected. IL-7 level was measured using enzyme linked immunosorbent assay (ELISA) and compared among all groups. The 130 ACS patients were followed up, and Logistic regression analysis was used to analyze the relationship between IL-7 level and prognosis. Results: Compared with healthy control group and SAP group, there was significant rise in IL-7 level in UAP group and AMI group [(1.84±0.47) pg/ml, (2.11±0.63) pg/ml vs. (4.87±0.52) pg/ml, (5.15±0.71) pg/ml, P0.05 both); Logistic regression analysis indicated that expression level of serum IL-7 was an independent risk factor for adverse cardiovascular events in ACS patients (OR=1.212, 95%CI:1.061-1.418). Conclusion: Interleukin-7, as an important inflammatory cytokines, its serum level abnormally elevated in patients with acute coronary syndrome, it may have important prognostic value.

PGC-1-related coactivator (PRC) negatively regulates endothelial adhesion of monocytes via inhibition of NF κB activity.

PGC-1-related coactivator (PRC) is a growth-regulated transcriptional cofactor known to activate many of the nuclear genes specifying mitochondrial respiratory function. Endothelial dysfunction is a prominent feature found in many inflammatory diseases. Adhesion molecules, such as VCAM-1, mediate the attachment of monocytes to endothelial cells, thereby playing an important role in endothelial inflammation. The effects of PRC in regards to endothelial inflammation remain unknown. In this study, our findings show that PRC can be inhibited by the inflammatory cytokine LPS in cultured human umbilical vein endothelial cells (HUVECs). In the presence of LPS, the expression of endothelial cell adhesion molecular, such as VCAM1 and E-selectin, is found to be increased. These effects can be negated by overexpression of PRC. Importantly, monocyte adhesion to endothelial cells caused by LPS is significantly attenuated by PRC. In addition, overexpression of PRC protects mitochondrial metabolic function and suppresses the rate of glycolysis against LPS. It is also found that overexpression of PRC decreases the transcriptional activity of NF-κB. These findings suggest that PRC is a negative regulator of endothelial inflammation.

Clinical study of myocardium injury in patients with severe brain injury / 中华急诊医学杂志

ObjectiveTo explore heart rate variability (HRV),cardiac troponin Ⅰ (cTnI),left ventricular ejection fraction (LVEF) and electrocardiogram (ECG) in order to clarify the function of cardiac autonomic nerve system and the incidence of potential myocardium injury in patients with severe brain injury.MethodsClinical data of 65 patients with severe brain injury admitted between June 2006 and June 2010 were reviewed.For the sake of comparison,patients were divided by different groupings as per different biomarkers or outcomes such as Glasgow coma scale (GCS) 6 - 8 group and GCS 3 - 5 group; cTnl ＞ 0.5 group,0.04 ＜ cTnl ＜ 0.5 group and CTnl ＜ 0.04 group; and survival group and death group.Another 30 healthy subjects were enrolled as control group.Heart rate variability (HRV) was analyzed with both timedomain and frequency domain methods based on data from 24-hour Holter monitoring.The level of serum cardiac troponin Ⅰ was detected. The left ventricular ejection fraction was measured by beside color ultrasonogram.The different relationships between HRV and GCS as well as prognosis,between cTnI and GCS as well as fatality,between cTnI and ECG,and between EF and GCS were analyzed.The computer statistical software SPSS version 13.0 was used for statistical analysis of data.ResultsAll of the 65 patents with severe brain injury were subjected to decrease in HRV.The patients of GCS 6 - 8 group and GCS 3 - 5 group showed significantly lowered HRV in comparison with control group ( P ＜ 0.05 ).The death group showed more obvious decrease in HRV than the survival group ( P ＜ 0.05 ).Fifty-one of the 65 patients had myocardial injury evidenced by increase in cardiac troponin Ⅰ.The patients of cTnl ＞0.5 group and 0.04 ＜cTnI ＜ 0.5 group showed significantly higher fatality compared with cTnI ＜ 0.04 group ( P ＜ 0.05 ).Compared with the GCS 6 ～ 8 group,more patients in the GCS 3 -5 group had abnormal serum CTnl level and lower EF.ConclusionsThere are cardiac autonomic nerve system disorders and different degrees of myocardial injury in patients with severe brain injury,and early intervention is essential to decrease the fatality of severe brain injury.

Protective effect of diallyl trisulfide on liver in rats with sepsis and the mechanism / 华中科技大学学报（医学）（英德文版）

The protective effects of diallyl trisulfide on liver were examined in rats with sepsis. Sepsis was reproduced in rats by cecum ligation and puncture (CLP). Fifty-six male Wistar rats were randomly divided into sham-operated group (group S, n=8), sepsis model group (group C, n=24), diallyl trisulfide (DATS)-treated group (group D, n=24). Animals in groups C and D were further divided into three subgroups according to different observation time points, with 8 rats in each subgroup· Rats in group D and C were intravenously injected with normal saline or DATS respectively at a dose of 20 mg/kg after the establishment of sepsis model. Eight rats in groups C and D were sacrificed at 3, 6 and 24 h post-CLP and their livers were harvested for detection of interleukin (IL)-1 receptor associated kinase-4 (IRAK-4), nuclear factor-κB (NF-κB), c-fos, c-jun, malondialdehydethhe (MDA) and superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α) and for pathological examination. The results showed that the levels of serum IRAK-4, NF-κB and TNF-α in hepatic tissues were higher in group C than group S (control group) (P<0.05). After DATS treatment, the levels of IRAK-4 and NF-κB in the hepatic tissues and serum TNF-α in group D were lower than those in group C (P<0.05). The levels of c-fos and c-jun and MDA in the hepatic tissues were higher in group C than in group S (P<0.05). After DATS treatment, the levels of c-fos and c-jun and MDA in the hepatic tissues were significantly lower in group D than in group C (P<0.05). When compared with group S group, concentration of SOD in the hepatic tissues in group C was significantly lower (P<0.05). After DATS treatment, the concentration of SOD in the hepatic tissues was higher in group D than in group C (P<0.05). These findings suggested that treatment with DATS could ameliorate sepsis-induced liver injury in rats. The protective effect might be related to its ability to inhibit the signal pathway of IRAK-4 and NF-κB, thereby decreasing the production of oxygen free radicals and down-regulating the expression of c-fos and c-jun.

Protective effect of diallyl trisulfide on liver in rats with sepsis and the mechanism / 华中科技大学学报（医学）（英德文版）

The protective effects of diallyl trisulfide on liver were examined in rats with sepsis. Sepsis was reproduced in rats by cecum ligation and puncture (CLP). Fifty-six male Wistar rats were randomly divided into sham-operated group (group S, n=8), sepsis model group (group C, n=24), diallyl trisulfide (DATS)-treated group (group D, n=24). Animals in groups C and D were further divided into three subgroups according to different observation time points, with 8 rats in each subgroup· Rats in group D and C were intravenously injected with normal saline or DATS respectively at a dose of 20 mg/kg after the establishment of sepsis model. Eight rats in groups C and D were sacrificed at 3, 6 and 24 h post-CLP and their livers were harvested for detection of interleukin (IL)-1 receptor associated kinase-4 (IRAK-4), nuclear factor-κB (NF-κB), c-fos, c-jun, malondialdehydethhe (MDA) and superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α) and for pathological examination. The results showed that the levels of serum IRAK-4, NF-κB and TNF-α in hepatic tissues were higher in group C than group S (control group) (P<0.05). After DATS treatment, the levels of IRAK-4 and NF-κB in the hepatic tissues and serum TNF-α in group D were lower than those in group C (P<0.05). The levels of c-fos and c-jun and MDA in the hepatic tissues were higher in group C than in group S (P<0.05). After DATS treatment, the levels of c-fos and c-jun and MDA in the hepatic tissues were significantly lower in group D than in group C (P<0.05). When compared with group S group, concentration of SOD in the hepatic tissues in group C was significantly lower (P<0.05). After DATS treatment, the concentration of SOD in the hepatic tissues was higher in group D than in group C (P<0.05). These findings suggested that treatment with DATS could ameliorate sepsis-induced liver injury in rats. The protective effect might be related to its ability to inhibit the signal pathway of IRAK-4 and NF-κB, thereby decreasing the production of oxygen free radicals and down-regulating the expression of c-fos and c-jun.

Protective effects of endotoxin pretreatment on hepatic tissue in rats with endotoxemia / 中华急诊医学杂志

Objective To investigate the protective effects of endotoxin precondition on hepatic tissue in rats with endotoxemia.Method The models of rats with acute endotoxemia were produced by injecting LPS directly.Seventy-two male wistar rats were randomly divided into three groups:saline control group(N,n=24),lipopolysaccharide (LPS)-treated group(L,n=24),LPS pretreated group(P,n=24).Each group was divid-ed into four subgroups:saline control and lipopolysaccharide (LPS)-treated 2 h,4 h,6 h,12 h groups and LPS-pretreated 2 h,4 h,6 h,12 h groups.Rats in group P were first administered with introperitoneal injection of 0.25 mg/kg LPS,and after 24 hours,the rats were injected with 0.5 mg/kg LPS.Rats in group N and group L received with an equivalent amount of saline.After 72 hours,rats in group L and group P were intravenonsly injected with 10 mg/kg LPS,and rats in group N received with an equivalent amount of saline.Six rats were killed at 2,4,6 and 12 hours after injection of LPS in group L and P.The hvers were removed for detecting Toll like receptor-4 (TLR-4),nuclear factor-кB(NF-кB),tumor Necrosis Factor-apha(TNF-α)and malondialdehyde(MDA).The blood was drawn for detecting Alamine aminotmnsferose (ALT) and Aspartate aminotransferose (AST).The patho-logical changes of liver were also examined.Software SPSS13.0 was utilized to do ANOVA for statistical analysis.Results The rats exposed to LPS alone demonstrated an increase in TLR-4.NF-кB and TNF-α activity of the liver tissue.Incontrast.the rats exporsed 10 LPS prelreatment exhibited a significant decrease in TLT-4,NF-кB and TNF-α activity.The contents of TLR-4,NF-кB and TNF-α of LPS-treated 4 h groupwere,(38.76±0.67),170.82 ±31.40),293.16±49.49)and(6.263±0.351),significantly higher than those of the saline control group.The administration of endotoxin pretreatment reduced the indexes to(22.35±1.35),(135.55±26.44)and(234.23±44.96),respectively(P＜0.05).Conclusions TLR-4,NF-кB and TNF-α take part in the progress of hepatic injury in rats with endotoxemia.Endotoxin pretreatment can eliminate hepatic injury and protect the hepatic tissue by downmgulating the levels of TLR-4.NF-кB and TNF-α.

Effects of Andrographitis Paniculata extracts on the expression of CD40 in endothelial cells / 华中科技大学学报（医学）（英德文版）

In order to investigate the expression of CD40 in endothelial cells (ECs) in a variety of injured conditions and the interventional role of Andrographitis Paniculata isolate (API(0134)), the thoracic aorta ECs of guinea pigs were cultured in vitro until the third passage, incubated in the presence of media containing xanthine oxidase (XO) and xanthine (Xan) which produced oxygen free radical (OFR group); oxidized-LDL (ox-LDL group); XO, Xan and API(0134) (OFR+API(0134) group); or ox-LDL and API(0134) (ox-LDL+API(0134) group). The expression of CD40 in ECs was detected by immunofluorescence assay and reverse transcription-PCR (RT-PCR). The results showed as compared with the control group, the expression of CD40 in ECs in OFR group and ox-LDL group was increased (P<0.01), but attenuated significantly in OFR+ API(0134) group and ox-LDL+API(0134) group (P<0.05). It was suggested that API(0134) could protect atherosclerosis by inhibiting the expression of CD40 molecule in injured ECs.

Effects of Andrographitis Paniculata Extracts on the Expression of CD40 in Endothelial Cells / 华中科技大学学报（医学）（英德文版）

In order to investigate the expression of CD40 in endothelial cells (ECs) in a variety of injured conditions and the interventional role of Andrographitis Paniculata isolate (API0134), the thoracic aorta ECs of guinea pigs were cultured in vitro until the third passage, incubated in the presence of media containing xanthine oxidase (XO) and xanthine (Xan) which produced oxygen free radical (OFR group); oxidized-LDL (ox-LDL group); XO, Xan and API0134 (OFR+API0134 group); or ox-LDL and API0134 (ox-LDL+API0134 group). The expression of CD40 in ECs was detected by immunofluorescence assay and reverse transcription-PCR (RT-PCR). The results showed as compared with the control group, the expression of CD40 in ECs in OFR group and ox-LDL group was increased (P＜0.01), but attenuated significantly in OFR+ API0134 group and ox-LDL+API0134 group (P＜0.05). It was suggested that API0134 could protect atherosclerosis by inhibiting the expression of CD40 molecule in injured ECs.

Sodium tanshinone IIA sulfonate depresses angiotensin II-induced cardiomyocyte hypertrophy through MEK/ERK pathway

Cardiomyocyte hypertrophy is a major cause of morbidity and mortality worldwide. The aim of this study is to determine the effects of sodium tanshinone IIA sulfonate (STS) on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) in vivo and in vitro. In long-term treatment, adult Wistar rats were infused with Ang II for three weeks via osmotic mini-pumps and some of them were given intragastrically of STS. Left ventricle was isolated; the ratio of left ventricular weight to body weight and systolic blood pressure (SBP) were determined and heart morphometry was assessed after hematoxylin and eosin staining. Results indicated STS inhibited Ang II-induced increases in myocyte diameter and decreased the LVW/BW ratio independent of decreasing systolic blood pressure. In vitro, treatment of cultured cardiomyocytes with STS inhibited Ang II-induced increase in cell size, protein synthesis, ANP expression, activation of extracellular signal-regulated kinase (ERK) and ERK kinase (MEK). Then we reexamined the mechanism of STS-induced anti-hypertrophic effects. Results revealed MEK inhibitor U0126 (20 microM) markedly enhanced STS-induced depressions in [3H]leucine incorporation and ANP expression. In conclusion, MEK/ERK pathway plays a significant role in the anti-hypertrophic effects of STS.

Experimental study on the preventive mechanism of salviae miltiorrhizae against atherosclerosis in rabbits models / 华中科技大学学报（医学）（英德文版）

The preventive mechanism of salviae miltiorrhizae (SM) against experimental atherosclerosis (AS) in rabbits models was investigated. The experimental AS rabbit models were reproduced by feeding the high cholesterol diet. The changes of atherosclerotic plaques in normal group, model group and SM treated group were observed. The levels of serum TG, TC, HDL-C and LDL-C were determined. The immunohistochemistry was used to detect the expression of Bcl-2, Bax and IL-6 proteins in atherosclerotic plaques. The results showed that the level of serum TG in SM treated group was significantly lower than in model group (P<0.01). Immunohistochemistry revealed that the expression of Bcl-2, Bax and TL-6 in model group was significantly higher than in normal group. In the SM group, the expression of Bcl-2 protein was up-regulated and that of Bax was down-regulated. It was suggested that SM could inhibit formation of AS in experimental rabbits. To decrease the expression of Bax and increase the expression of Bcl-2 protein may be one of the mechanisms of SM against atherosclerosis.

Experimental study on the preventive mechanism of salviae miltiorrhizae against atherosclerosis in rabbits models / 华中科技大学学报（医学）（英德文版）

The preventive mechanism of salviae miltiorrhizae (SM) against experimental atherosclerosis (AS) in rabbits models was investigated. The experimental AS rabbit models were reproduced by feeding the high cholesterol diet. The changes of atherosclerotic plaques in normal group, model group and SM treated group were observed. The levels of serum TG, TC, HDL-C and LDL-C were determined. The immunohistochemistry was used to detect the expression of Bcl-2, Bax and IL-6 proteins in atherosclerotic plaques. The results showed that the level of serum TG in SM treated group was significantly lower than in model group (P<0.01). Immunohistochemistry revealed that the expression of Bcl-2, Bax and TL-6 in model group was significantly higher than in normal group. In the SM group, the expression of Bcl-2 protein was up-regulated and that of Bax was down-regulated. It was suggested that SM could inhibit formation of AS in experimental rabbits. To decrease the expression of Bax and increase the expression of Bcl-2 protein may be one of the mechanisms of SM against atherosclerosis.