Publications by authors named "Zhi-Tao Yang"

28 Publications

  • Page 1 of 1

Mucin 1 Inhibits Ferroptosis and Sensitizes Vitamin E to Alleviate Sepsis-Induced Acute Lung Injury through GSK3/Keap1-Nrf2-GPX4 Pathway.

Oxid Med Cell Longev 2022 21;2022:2405943. Epub 2022 Jul 21.

Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Ferroptosis is a nonapoptotic form of programmed cell death, which may be related to the occurrence and development of sepsis-induced acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). Mucin 1 (MUC1) is a kind of macromolecule transmembrane glycoprotein. Previous studies have shown that MUC1 could relieve ALI in sepsis and predict whether sepsis patients would develop into ARDS. However, the role of MUC1 in the ferroptosis of sepsis-induced ALI/ARDS remains unclear.

Materials And Methods: Sera samples from 50 patients with sepsis/septic shock were used to detect iron metabolism-related markers. Western blot and qRT-PCR were conducted to detect the expression levels of ferroptosis-related genes. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate inflammatory factors. Transmission electron microscopy (TEM) was used to assess morphological changes of cells.

Results: The results showed that the iron metabolism-related indicators in sepsis-induced ARDS patients changed significantly, suggesting the iron metabolism disorder. The expression levels of ferroptosis-related genes in lung tissues of sepsis had marked changes, and the lipid peroxidation levels increased, while Ferrostatin-1 (Fer-1) could reverse the above results, which confirmed the occurrence of ferroptosis. In terms of mechanism studies, inhibition of MUC1 dimerization could increase the expression level of Keap1, reduce the phosphorylation level of GSK3, inhibit the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4, enhance the lipid peroxidation level of lung tissues, trigger ferroptosis, and aggravate lung injury. Besides, inhibiting MUC1 reversed the alleviating effect of vitamin E on ALI caused by sepsis, increased the aggregation of inflammatory cells in lung tissues, and aggravated alveolar injury and edema.

Conclusions: Our study was the first to explore the changes of iron metabolism indicators in ALI/ARDS of sepsis, clarify the important role of ferroptosis in ALI/ARDS induced by sepsis, and reveal the effects and specific mechanisms of MUC1 in regulating ferroptosis, as well as the sensitization on vitamin E.
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http://dx.doi.org/10.1155/2022/2405943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334047PMC
August 2022

[Comparative study on arthroscopic double posterior medial approach versus open surgery for acute simple posterior cruciate ligament tibial avulsion fracture].

Zhongguo Gu Shang 2022 Jun;35(6):506-11

Department of Orthopaedics, the Second Hospital of Lanzhou University, Lanzhou 730030, Gansu, China.

Objective: To compare difference in clnical efficacy between arthroscopic double posterior internal approach and incisional surgery for acute simple posterior cruciate ligament tibial avulsion fractures.

Methods: Totally 52 patients with acute simple posterior cruciate ligament tibial avulsion fractures treated from June 2016 to June 2020 were retrospectively analyzed and divided into two groups according to different surgical protocols, 27 patients in arthroscopic group were treated with arthroscopic double posterior internal approach, including 16 males and 11 females, aged from 19 to 52 years old, with an average age of (34.9±9.2) years old;25 patients in open reduction group were treated with posterior medial knee incision, including 14 males and 11 females, aged from 18 to 54 years old , with an average age of(33.7±8.4) years old. Operation time, incision length, intraoperative bleeding, hospitalization days, hospitalization cost, fracture healing, complications, postoperative Lysholm score and IKDC score at 12 months were observed and compared between two groups.

Results: All patients in both groups were completed opertaion successfully without vascular or nerve injury, and 52 patients were followed up from 6 to 24 months with an average of (15.0±1.7) months. Operation time and hospitalization cost in arthroscopic group were significantly greater than those in open reduction group(<0.05);intraoperative bleeding, incision length, and hospitalization days in arthroscopic group were less than those in open reduction group(<0.05);preoperative Lysholm score in arthroscopic group and open reduction group were 49.1±2.3 and 48.9±1.1 respectively, and improved to 95.9±1.7 and 86.4±1.2 at 12 months after operation respectively(<0.05);preoperative IKDC scores in arthroscopic group and open reduction group were 47.6±4.1 and 48.1±3.9 respectively, and improved to 96.9±1.5 and 87.1±1.4 at 12 months after operation(<0.05).

Conclusion: Arthroscopic double posterior internal approach for acute simple posterior cruciate ligament tibial stop avulsion fracture has satisfactory early results and better efficacy than traditional open surgery, which has advantages of less trauma, faster recovery and easier operation.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2022.06.002DOI Listing
June 2022

[Early efficacy analysis on arthroscopic autologous osteochondral grafting in the treatment of recurrent anterior shoulder dislocation].

Zhongguo Gu Shang 2022 Mar;35(3):233-7

Department of Orthopaedics, the Second Hospital of Lanzhou University, Lanzhou 730030, Gansu, China.

Objective: To investigate the early efficacy of arthroscopic autologous osteochondral grafting in the treatment of recurrent anterior shoulder dislocation.

Methods: From January 2019 to January 2021, 17 patients with recurrent anterior dislocation of shoulder who underwent arthroscopic autologous osteochondral grafting were selected, including 12 males and 5 females, ranging in age from 17 to 55 years old, with a mean of (32.88±12.33) years old. Rowes rating system for Bankart repair(Rowe), Oxford Shoulder Instability Score (OSIS) and Simple Shoulder Test (SST) were compared before operation, 6 months after operation and at the latest follow-up. OSIS and SST used to evaluate shoulder function were recorded before surgery and at the latest follow-up. The shoulder mobility and intraoperative and postoperative complications were also recorded.

Results: All 17 patients were followed up, and the duration ranged from 7 to 25 months, with a mean of (18.4±5.4) months. During the follow-up period, there was no re-dislocation, no vascular or nerve injury. Rowe score increased from 26.2±6.0 before operation to 74.4±4.0 and 82.4±3.1 after 6 months and the latest follow-up. There was significant difference in Rowe score between different time points after operation and before operation (<0.05). The OSIS increased from 37.0±3.6 before operation to 47.4±2.6 and 52.7±2.6 after 6 months and the latest follow-up. There was significant difference in OSIS between different time points after operation and before operation (<0.05). The SST score increased from 6.8±0.7 before operation to 9.8±0.8, 11.6±2.6 after 6 months and the latest follow-up. There was significant difference in SST score between different time points after operation and before operation (<0.05). At the latest follow-up, the lateral external rotation and abduction external rotation activities of the patient were significantly improved compared with those before operation.

Conclusion: This study provides preliminary evidence that arthroscopic autologous osteochondral grafting can achieve satisfactory early clinical outcomes and stability in patients with recurrent anterior shoulder dislocation with glenoid fracture and defect less than <20%, which is a reliable and effective procedure.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2022.03.007DOI Listing
March 2022

Free fatty acids-induced neutrophil extracellular traps lead to dendritic cells activation and T cell differentiation in acute lung injury.

Aging (Albany NY) 2021 12 27;13(24):26148-26160. Epub 2021 Dec 27.

Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

This study aimed to investigate whether free fatty acids (FFAs) could induce the release of neutrophil extracellular traps (NETs), as well as the mechanism of FFAs-induced NETs in acute lung injury (ALI). FFAs were used to induce NETs production. The reactive oxygen species (ROS) production was detected after FFA and NADPH oxidase inhibitor treatments. The association between FFAs-induced NETs and the activation of p38, ERK, and JNK pathways was investigated. The effect of FFAs-induced NETs on the dendritic cells (DCs) activation and T cell differentiation was investigated. FFAs could induce neutrophils to produce NETs. FFAs significantly promoted ROS production and increased the expression of ERK, p38 and JNK, and treatment of the inhibitors of NAPDH oxidase (DPI), p38 (SB202190), ERK1/2 (U0126) and JNK (SP600125) inhibited FAAs-induced NETs production. FFAs induced NETs could promote DCs activation and consequently led to the differentiation of primary CD4+ T cells into Th1 and Th17 cells and the release of IL-1β, IL-12 and TNF-α. FFAs are capable of inducing NETs via NOX, ERK, p38 and JNK pathways. FFA-induced NETs further lead to DCs activation and T cell differentiation, which can well explain the mechanism of ALI caused by FFAs.
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http://dx.doi.org/10.18632/aging.203802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751615PMC
December 2021

Giant cell tumors of the mobile spine with invasion of adjacent vertebrae: an unusual imaging finding.

BMC Musculoskelet Disord 2021 Aug 24;22(1):726. Epub 2021 Aug 24.

Department of Radiology, The affiliated hospital of Qingdao University, Qingdao, 266003, China.

Background: Giant cell tumors of the mobile spine invasion of the adjacent vertebrae are an ignored imaging finding.

Methods: Nine patients with giant cell tumors of the mobile spine with invasion of the adjacent vertebrae confirmed by pathology were enrolled. Eight patients had pure giant cell tumors (GCTs), while one patient also had an aneurysmal bone cyst. All patients underwent conventional computed tomography, three-dimensional reconstruction, and conventional magnetic resonance imaging, while seven patients also underwent post-contrast magnetic resonance imaging.

Results: All patients showed GCTs of the mobile spine that arose from the vertebral body and extended to the vertebral arch. The tumors showed soft-tissue attenuation with no evidence of a mineralized matrix. Pathological fracture was seen in five patients. The margin of the original tumor showed partial sclerosis in four patients and involved an adjacent vertebral body with a sclerotic rim in two patients. The tumors showed a homogeneous and similar signal intensity to the normal spinal cord on T1WI (T1-weighted image) in five patients. The cystic area of the tumors was hyperintense on T2WI in the remaining four patients, while one patient showed hemorrhage that was hyperintense on T1WI. The solid components of the GCTs show marked enhancement in all cases, while the cystic area of the tumors was observed without enhancement on contrast-enhanced images in four patients. Bone destruction of the adjacent vertebral body showed a homogeneous signal on T1WI and T2WI and marked enhancement on contrast-enhanced images.

Conclusions: Giant cell tumors of the mobile spine with invasion into adjacent vertebrae are an unusual imaging finding. Radiologists should be familiar with this imaging characteristic.
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http://dx.doi.org/10.1186/s12891-021-04610-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385806PMC
August 2021

A CT-based radiomics nomogram for differentiation of squamous cell carcinoma and non-Hodgkin's lymphoma of the palatine tonsil.

Eur Radiol 2022 Jan 8;32(1):243-253. Epub 2021 Jul 8.

Department of Radiology, The Affiliated Hospital of Qingdao University, NO. 16, Jiangsu Road, Qingdao, 266000, China.

Objectives: Accurate preoperative differentiation between squamous cell carcinoma (SCC) and non-Hodgkin's lymphoma (NHL) in the palatine tonsil is crucial because of their different treatment. This study aimed to construct and validate a contrast-enhanced CT (CECT)-based radiomics nomogram for preoperative differentiation of SCC and NHL in the palatine tonsil.

Methods: This study enrolled 135 patients with a pathological diagnosis of SCC or NHL from two clinical centers, who were divided into training (n = 94; SCC = 50, NHL = 44) and external validation sets (n = 41; SCC = 22, NHL = 19). A radiomics signature was constructed from radiomics features extracted from routine CECT images and a radiomics score (Rad-score) was calculated. A clinical model was established using demographic features and CT findings. The independent clinical factors and Rad-score were combined to construct a radiomics nomogram. Performance of the clinical model, radiomics signature, and nomogram was assessed using receiver operating characteristics analysis and decision curve analysis.

Results: Eleven features were finally selected to construct the radiomics signature. The radiomics nomogram incorporating gender, mean CECT value, and radiomics signature showed better predictive value for differentiating SCC from NHL than the clinical model for training (AUC, 0.919 vs. 0.801, p = 0.004) and validation (AUC, 0.876 vs. 0.703, p = 0.029) sets. Decision curve analysis demonstrated that the radiomics nomogram was more clinically useful than the clinical model.

Conclusions: A CECT-based radiomics nomogram was constructed incorporating gender, mean CECT value, and radiomics signature. This nomogram showed favorable predictive efficacy for differentiating SCC from NHL in the palatine tonsil, and might be useful for clinical decision-making.

Key Points: • Differential diagnosis between SCC and NHL in the palatine tonsil is difficult by conventional imaging modalities. • A radiomics nomogram integrated with the radiomics signature, gender, and mean contrast-enhanced CT value facilitates differentiation of SCC from NHL with improved diagnostic efficacy.
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http://dx.doi.org/10.1007/s00330-021-08153-9DOI Listing
January 2022

Epidemiology, species distribution, and outcome of nosocomial Candida spp. bloodstream infection in Shanghai: an 11-year retrospective analysis in a tertiary care hospital.

Ann Clin Microbiol Antimicrob 2021 May 13;20(1):34. Epub 2021 May 13.

Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Background: The incidence of Candida bloodstream infections (BSIs), has increased over time. In this study, we aimed to describe the current epidemiology of Candida BSI in a large tertiary care hospital in Shanghai and to determine the risk factors of 28-day mortality and the impact of antifungal therapy on clinical outcomes.

Methods: All consecutive adult inpatients with Candida BSI at Ruijin Hospital between January 1, 2008, and December 31, 2018, were enrolled. Underlying diseases, clinical severity, species distribution, antifungal therapy, and their impact on the outcomes were analyzed.

Results: Among the 370 inpatients with 393 consecutive episodes of Candida BSI, the incidence of nosocomial Candida BSI was 0.39 episodes/1000 hospitalized patients. Of the 393 cases, 299 (76.1%) were treated with antifungal therapy (247 and 52 were treated with early appropriate and targeted antifungal therapy, respectively). The overall 28-day mortality rate was 28.5%, which was significantly lower in those who received early appropriate (25.5%) or targeted (23.1%) antifungal therapy than in those who did not (39.4%; P = 0.012 and P = 0.046, respectively). In multivariate Cox regression analysis, age, chronic renal failure, mechanical ventilation, and severe neutropenia were found to be independent risk factors of the 28-day mortality rate. Patients who received antifungal therapy had a lower mortality risk than did those who did not.

Conclusions: The incidence of Candida BSI has increased steadily in the past 11 years at our tertiary care hospital in Shanghai. Antifungal therapy influenced short-term survival, but no significant difference in mortality was observed between patients who received early appropriate and targeted antifungal therapy.
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http://dx.doi.org/10.1186/s12941-021-00441-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120712PMC
May 2021

Low fluid intake volume during the first 24 h and persistent negative fluid balance from the second day are associated with favorable prognosis for patients with sepsis.

Exp Ther Med 2021 Apr 23;21(4):387. Epub 2021 Feb 23.

Department of Emergency, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.

For patients with sepsis and septic shock, it remains controversial when to restrict fluid intake and achieve a negative fluid balance. The present study aimed to evaluate the effects of the fluid intake volume during the first 24 h as well as fluid balance for 7 days on the prognosis of sepsis or septic shock. A total of 337 patients diagnosed with sepsis or septic shock at Ruijin Hospital (Shanghai, China) were enrolled in the present retrospective study. Patients with a low fluid intake volume during the first 24 h (fluid intake, 28.1±10.6 ml/kg) had lower in-hospital mortality rates (18.0 vs. 27.3%, P=0.043) and a shorter duration of mechanical ventilation [0 (0-6) vs. 3 (0-11), P=0.025] than the high-fluid volume intake group (62.6±17.6 ml/kg). Furthermore, survivors exhibited a daily negative net fluid balance from the second day (48 h), whereas non-survivors had a daily positive net fluid balance for 7 days, where fluid balance volumes were significantly lower in survivors compared with those in non-survivors. Finally, binary logistic regression analysis was used to determine whether the mean daily fluid balance (P<0.001) and the Acute Physiologic and Chronic Health Evaluation II score (P=0.048) were independent prognostic factors for patients with sepsis or septic shock. It was indicated that a low fluid intake volume during the first 24 h and a persistent negative fluid balance from the second day were associated with favorable outcomes. The mean daily fluid balance was an independent prognostic factor or patients with sepsis or septic shock.
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http://dx.doi.org/10.3892/etm.2021.9818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918047PMC
April 2021

A higher dose of vancomycin is needed in critically ill patients with augmented renal clearance.

Transl Androl Urol 2020 Oct;9(5):2166-2171

Department of Pharmacy, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Using standard vancomycin dosage in critically ill patients might lead to therapy failure and worse patient outcomes, augmented renal clearance (ARC) may be the leading risk factor. In this study, we comprehensively investigated the pharmacokinetics-pharmacodynamics (PK-PD) of vancomycin in critically ill patients with ARC, hoping to explore the precise and accurate dose adjustment method for vancomycin.

Methods: All critically ill patients tested for steady-state trough vancomycin serum concentrations during the recent 6 years in a tertiary level hospital were collected retrospectively and divided into ARC and non-ARC groups, respectively, according to creatinine clearance (CLcr). Serum vancomycin concentrations were measured by the fluorescence polarization immunoassay method. PK-PD parameters of vancomycin were recorded or calculated. The desired daily dose successful in achieving the lower target trough levels (10 mg/L) of vancomycin were investigated correspondingly.

Results: A total of 280 vancomycin concentrations were eligible for analysis. The ARC group (n=139) contained more male patients (64.7%) with average age and CLcr of 40 years old (P<0.05) and 180.8 mL/min (P<0.001), respectively. Those patients exhibited higher clearance (CL) and lower trough serum concentrations than the non-ARC patients under comparable daily doses of vancomycin. All the ICU patients demonstrated lower AUC values than the target level of 400 µg·h/mL, and this value showed a lower trend in the ARC group than the non-ARC group (232.9 316.2 µg·h/mL). Subtherapeutic trough concentrations of vancomycin (<10.0 mg/L) were observed in 77.7% and 68.8% of the ARC and non-ARC patients (P<0.05). The proportion of patients with a trough concentration of 10-15 and 15-20 mg/L was 17.9% and 4.3%, respectively, in the ARC group and 24.8% and 2.8%, respectively, in the non-ARC group., a daily dose of 46.0 and 35.5 mg/kg of vancomycin is needed, respectively, in the ARC and non-ARC group to achieve a target trough concentration of 10 mg/L.

Conclusions: A higher dose of vancomycin is needed in critically ill patients, especially those with ARC, and appropriate TDM-guided dose adjustment should be considered to achieve the targeted therapeutic range and to provide dosing guidance for this: patient population.
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http://dx.doi.org/10.21037/tau-20-1048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658164PMC
October 2020

Identification of Potential Biomarkers and Immune Features of Sepsis Using Bioinformatics Analysis.

Mediators Inflamm 2020 9;2020:3432587. Epub 2020 Oct 9.

Department of Emergency in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Sepsis remains a major global concern and is associated with high mortality and morbidity despite improvements in its management. Markers currently in use have shortcomings such as a lack of specificity and failures in the early detection of sepsis. In this study, we aimed to identify key genes involved in the molecular mechanisms of sepsis and search for potential new biomarkers and treatment targets for sepsis using bioinformatics analyses. Three datasets (GSE95233, GSE57065, and GSE28750) associated with sepsis were downloaded from the public functional genomics data repository Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using R packages (Affy and limma). Functional enrichment of the DEGs was analyzed with the DAVID database. Protein-protein interaction networks were derived using the STRING database and visualized using Cytoscape software. Potential biomarker genes were analyzed using receiver operating characteristic (ROC) curves in the R package (pROC). The three datasets included 156 whole blood RNA samples from 89 sepsis patients and 67 healthy controls. Between the two groups, 568 DEGs were identified, among which 315 were upregulated and 253 were downregulated in the septic group. These genes were enriched for pathways mainly involved in the innate immune response, T-cell biology, antigen presentation, and natural killer cell function. ROC analyses identified nine genes-LRG1, ELANE, TP53, LCK, TBX21, ZAP70, CD247, ITK, and FYN-as potential new biomarkers for sepsis. Real-time PCR confirmed that the expression of seven of these genes was in accordance with the microarray results. This study revealed imbalanced immune responses at the transcriptomic level during early sepsis and identified nine genes as potential biomarkers for sepsis.
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http://dx.doi.org/10.1155/2020/3432587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568774PMC
October 2021

Effects of fluid balance on prognosis of acute respiratory distress syndrome patients secondary to sepsis.

World J Emerg Med 2020 ;11(4):216-222

Department of Emergency, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Fluid management is crucial to acute respiratory distress syndrome (ARDS) secondary to sepsis. However, choices of fluid resuscitation strategies and fluid input volumes remain a thorny problem. Our study aimed to elucidate the relationship between fluid balance and prognosis of ARDS patients secondary to sepsis.

Methods: Our study included 322 sepsis patients from Ruijin Hospital between 2014 and 2018, and 84 patients were diagnosed as ARDS within 72 hours after onset of sepsis according to Berlin ARDS Definition.

Results: Among the 322 sepsis patients, 84 (26.1%) were complicated with ARDS within 72 hours. ARDS patients had a lower oxygenation index (PaO/FiO 166.4±71.0 vs. 255.0±91.2, <0.05), longer duration of mechanical ventilation (11 [6-24] days vs. 0 [0-0] days, <0.05) than those without ARDS. Sepsis patients with ARDS showed daily positive net fluid balance during seven days compared with those without ARDS who showed daily negative net fluid balance since the second day with significant statistical differences. Among the 84 sepsis patients with ARDS, 58 (69.0%) died. Mean daily fluid input volumes were much lower in survivors than in non-survivors (43.2±16.7 mL/kg vs. 51.0±25.2 mL/kg, <0.05) while output volumes were much higher in survivors (45.2±19.8 mL/kg vs. 40.2±22.7 mL/kg, <0.05). Using binary logistic regression analysis, we found that the mean daily fluid balance was independently associated with mortality of sepsis patients complicating with ARDS (<0.05).

Conclusions: Early negative fluid balance is independently associated with a better prognosis of sepsis patients complicated with ARDS.
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http://dx.doi.org/10.5847/wjem.j.1920-8642.2020.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517398PMC
January 2020

High-dose vitamin C alleviates pancreatic injury via the NRF2/NQO1/HO-1 pathway in a rat model of severe acute pancreatitis.

Ann Transl Med 2020 Jul;8(14):852

Department of Emergency in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Oxidative stress plays a pivotal role in the progress of severe acute pancreatitis (SAP). Vitamin C (VC) is the most important antioxidant in plasma. However, the effects of an intravenous administration of high-dose VC and the mechanisms by which it exerts its antioxidant function in an experimental model of SAP have not been determined.

Methods: Sodium taurocholate was used to induce rat pancreatic injury and AR42J cells injury. After the establishment of SAP model, SAP rat and injured AR42J cells were treated with VC. For the injured AR42J cells, small interfering RNA-mediated knockdown of NRF2 was conducted after VC treatment. The histopathological characteristics, the apoptosis of pancreatic acinar cells, oxidative stress markers and levels of enzymes, biochemical indicators, and inflammatory cytokines were examined and . Furthermore, the mortality of rats was assessed.

Results: and results demonstrated that VC treatment ameliorated apoptosis of pancreatic acinar cells, as evidenced by the increase in Bcl-2, Bcl-XL, and MCL-1 expressions and decrease in Bax and cleaved caspase-3 expression along with decreased TUNEL-positive cells. Also, we found that the elevation of MDA and decrease of SOD, GPx, GSH/GSSG, and T-AOC induced by SAP were reversed by VC treatment and , and VC treatment increased expressions of Nrf2, NQO1, and HO-1 in SAP model at protein and gene level, indicating that VC attenuated oxidative stress via the NRF2/NQO1/HO-1 pathway. Meanwhile, it was found that sodium taurocholate significantly induced the release of amylase, lipase, IL-1β, and IL-6 in rat plasma and AR42J cells, which were declined by VC treatment. results also revealed that these alterations in sodium taurocholate-injured AR42J cells due to VC treatment was attenuated by NRF2 knockdown. In addition, VC at a dose of 500 mg/kg decreased the levels of lactic acid, Cre, NGAL, AST, and ALT in the plasma of SAP rats, suggesting the improvement of renal and pancreatic injury and liver function of SAP rats. Furthermore, the mortality of SAP rats was 50%, which declined to 30% after VC treatment.

Conclusions: The present study suggests that high-dose of VC ameliorate pancreatic injury of SAP via the NRF2/NQO1/HO-1 pathway to inhibit oxidative stress.
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http://dx.doi.org/10.21037/atm-19-4552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396777PMC
July 2020

Protective and predictive role of Mucin1 in sepsis-induced ALI/ARDS.

Int Immunopharmacol 2020 Jun 1;83:106438. Epub 2020 Apr 1.

Department of Emergency in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. Electronic address:

Objective: We aimed to investigate whether inhibition of MUC1 would aggravate sepsis-induced ALI, and explore the predictive value of plasma MUC1 for sepsis patients with or without ARDS.

Materials And Methods: MUC1 siRNA pre-treatment was used to knockdown MUC1 expression in vitro. GO203 was used to inhibit the homodimerization of MUC1-C in vivo. Expression levels of MUC1, TLR 4 and HIF-1α were detected by Western blot. In addition, plasma MUC1 levels of enrolled patients were detected by ELISA on the day of admission and on the 3rd day. ROC curve was used to determine the predictive value of MUC1 in sepsis patients with ARDS.

Results: Our results showed that inhibition of MUC1 could aggravate sepsis-induced acute lung injury and increase the expression of inflammatory cytokines in sera and BALF of sepsis mice. At the same time, we confirmed that inhibition of MUC1 could significantly decrease HIF-1α expression and thereby activate the expression level of TLR4. HIF-1α was a negative regulator of TLR-4. In addition, plasma MUC1 levels of sepsis patients with ARDS were significantly higher than those without ARDS and healthy adults. ROC curve showed that predictive value of plasma MUC1 on sepsis with ARDS on the 3rd day of enrollment was higher than the day of enrollment.

Conclusion: MUC1 could inhibit the expression of TLR-4 by stabilizing HIF-1α, thereby alleviate sepsis-induced lung injury and protect organ function. At the same time, elevated MUC1 levels in plasma had a good predictive valud on whether patients with sepsis would develop ARDS.
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http://dx.doi.org/10.1016/j.intimp.2020.106438DOI Listing
June 2020

Paclitaxel alleviated sepsis-induced acute lung injury by activating MUC1 and suppressing TLR-4/NF-κB pathway.

Drug Des Devel Ther 2019 24;13:3391-3404. Epub 2019 Sep 24.

Department of Emergency, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Purpose: It has been reported that approximately 40% of ALI (acute lung injury) incidence resulted from sepsis. Paclitaxel, as a classic anti-cancer drug, plays an important role in the regulation of inflammation. However, we do not know whether it has a protective effect against CLP (cecal ligation and puncture)-induced septic ALI. Our study aims to illuminate the mitigative effects of paclitaxel on sepsis-induced ALI and its relevant mechanisms.

Materials And Methods: The survival rates and organ injuries were used to evaluate the effects of paclitaxel on CLP mice. The levels of inflammatory cytokines were tested by ELISA. MUC1 siRNA pre-treatment was used to knockdown MUC1 expression in vitro. GO203 was used to inhibit the homodimerization of MUC1-C in vivo. The expression levels of MUC1, TLR 4 and p-NF-κB/p65 were detected by Western blot.

Results: Our results showed that paclitaxel improved the survival rates and ameliorated organ injuries especially lung injury in CLP-induced septic mice. These were accompanied by reduced inflammatory cytokines in sera and BALF (bronchoalveolar lavage fluid). We also found paclitaxel could attenuate TLR 4-NF-κB/p65 activation both in lung tissues of septic mice and LPS-stimulated lung type II epithelial cell line A549. At the upstream level, paclitaxel-upregulated expression levels of MUC1 in both in vivo and in vitro experiments. The inhibitory effects of paclitaxel on TLR 4-NF-κB/p65 activation were reversed in lung tissues of septic mice pre-treated with MUC1 inhibitor and in MUC1-knockdown A549 cells. Protection of paclitaxel on sepsis-induced ALI and decrease of inflammatory cytokines were also abolished by inhibition of MUC1.

Conclusion: Collectively, these results indicated paclitaxel could significantly alleviate acute lung injury in CLP-induced septic mice and LPS-stimulated lung type II epithelial cell line A549 by activating MUC1 and suppressing TLR-4/NF-κB pathway.
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http://dx.doi.org/10.2147/DDDT.S222296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766586PMC
April 2020

Intensive blood pressure control in patients with acute type B aortic dissection (RAID): study protocol for randomized controlled trial.

J Thorac Dis 2017 May;9(5):1369-1374

Department of Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.

Background: Blood pressure control is an essential therapy for patients with acute type B aortic dissection (ABAD) and should be maintained throughout the entire treatment. Thus, vast majority current guidelines recommend control the blood pressure to lower than 140/90 mmHg. Theoretically, a much lower target may further decrease the risk of propagation of dissection. However, some argued that too lower blood pressure would compromise the organ perfusion. Thus, there is no unanimous optimal target for blood pressure in patients with ABAD so far. The present study aimed to investigate the optimal blood pressure target for patients with ABAD, in the hope that the result would optimize the treatment of aortic dissection (AD).

Methods: The study is a multi-center randomized controlled clinical trial. Study population will include patients with new diagnosed ABAD and hypertension. Blocked randomization was performed where intensive blood pressure control (<120 mmHg) with conventional blood pressure control (<140 mmHg) were allocated at random in a ratio of 1:1 in blocks of sizes 4, 6, 8, and 10 to 360 subjects. Interim analysis will be performed. The primary outcome is a composite in-hospital adverse outcome, including death, permanent paraplegia or semi- paralysis during the hospitalization, and renal failure requiring hemodialysis at discharge. While the secondary outcomes include the aortic size, lower extremity or visceral ischemia, retrograde propagation into aortic arch or ascending aorta, mortality in 6 months and 1 year, intensive care unit (ICU) length of stay, total length of hospital stay, creatinine level, and surgical or endovascular intervention.

Ethics And Dissemination: The study was approved by the institutional review board of Sir Run Run Shaw Hospital (approval number: 20160920-9). Informed consent will be obtained from participants or their next-of-kin. The results will be published in a peer-reviewed journal and shared with the worldwide medical community.

Trial Registration: NCT03001739 (https://register.clinicaltrials.gov/).
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http://dx.doi.org/10.21037/jtd.2017.03.180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465133PMC
May 2017

Clinical features and viral quasispecies characteristics associated with infection by the hepatitis B virus G145R immune escape mutant.

Emerg Microbes Infect 2017 Mar 22;6(3):e15. Epub 2017 Mar 22.

Clinical Virology Research Laboratory, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

Coexistence of the hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) is an uncommon phenomenon, and the underlying mechanisms remain largely unknown. Amino-acid (aa) substitution from glycine to arginine at aa 145 (G145R), in the major hydrophilic region, has been reported in patients with HBsAg and anti-HBs coexistence. However, there is limited knowledge about the clinical features and viral quasispecies characteristics associated with G145R mutant hepatitis B virus (HBV) infection. We herein describe the dynamic changes in the serological and virological markers in a case of hepatitis B with coexisting HBsAg and anti-HBs, caused by a G145R immune escape mutant (genotype C). Entecavir was administered during the 4th week after admission. Alanine aminotransferase peaked in the 16th week, while both the HBsAg and HBeAg declined rapidly. HBsAg clearance and hepatitis B e antigen (HBeAg)/hepatitis B e antibody (anti-HBe) seroconversion were achieved in the 36th week, and then entecavir was withdrawn. A follow-up of 96 weeks showed that HBV DNA remained undetectable and that anti-HBs was maintained above 100 mIU/mL. The quasispecies characteristics of the G145R mutant HBV were investigated via ultra-deep sequencing. The complexity and genetic distance of the S and RT regions were much higher in the 8th week than at baseline or in the 4th week. Moreover, the frequencies of mutations (L173P, Q181R and A184V) in cytotoxic T lymphocyte epitopes increased before entecavir treatment. These findings extend understanding of the evolution of HBV under host immune pressure and of the clinical outcomes of affected patients.
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http://dx.doi.org/10.1038/emi.2017.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378923PMC
March 2017

Characteristics of CpG Islands and their quasispecies of full-length hepatitis B virus genomes from patients at different phases of infection.

Springerplus 2016 21;5(1):1630. Epub 2016 Sep 21.

Clinical Virology Research Laboratory, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025 China.

Background: CpG islands in hepatitis B virus (HBV) genome are potential targets for methylation mediated gene silencing, and may be involved in the pathogenesis of HBV infection. To date, their characteristics in HBV quasispecies (QS) remain largely unknown. The purpose of this study was to investigate the characteristics of CpG islands in HBV QS.

Methods: Forty patients diagnosed as acute hepatitis B (AHB, n = 10), immune-tolerant HBV carriers (IT, n = 9), chronic hepatitis B (CHB, n = 11), or acute on chronic liver failure (ACLF, n = 10), were enrolled in this case-control study. A total of 599 clones were isolated, and full-length HBV genomes were sequenced.

Results: CpG island II (CGII) in AHB group was shorter in length and its QS heterogeneity was lower than that in the chronic infection group. Among the chronic infection subgroups, CGII and CpG island III (CGIII) in IT group were longer and their heterogeneity was lower compared to CHB and ACLF groups. Length of CGII correlated with HBV DNA levels positively while the complexity and diversity of CGII correlated with HBV DNA levels negatively. Moreover, CGII and CGIII were shorter in genotype B than those in genotype C, while QS complexity and diversity of either CGII or CGIII had no significant difference between genotype B and C.

Conclusions: Overall, our results suggest that the distribution, length and QS heterogeneity of CpG islands in full-length HBV genome differ across clinical phases of infection, of which the mechanism warrants further study.
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http://dx.doi.org/10.1186/s40064-016-3192-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031574PMC
September 2016

Vitamin C Attenuates Hemorrhagic Shock-induced Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Nonintegrin Expression in Tubular Epithelial Cells and Renal Injury in Rats.

Chin Med J (Engl) 2016 Jul;129(14):1731-6

Department of Emergency Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Background: The expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases, but whether it takes place in renal tissues during hemorrhagic shock (HS) is unknown. The present study aimed to investigate this phenomenon and the inhibitory effect of Vitamin C (VitC).

Methods: A Sprague-Dawley rat HS model was established in vivo in this study. The expression level and location of DC-SIGN were observed in kidneys. Also, the degree of histological damage, the concentrations of tumor necrosis factor-μ and interleukin-6 in the renal tissues, and the serum concentration of blood urea nitrogen and creatinine at different times (2-24 h) after HS (six rats in each group), with or without VitC treatment before resuscitation, were evaluated.

Results: HS induced DC-SIGN expression in rat tubular epithelial cells. The proinflammatory cytokine concentration, histological damage scores, and functional injury of kidneys had increased. All these phenomena induced by HS were relieved when the rats were treated with VitC before resuscitation.

Conclusions: The results of the present study illustrated that HS could induce tubular epithelial cells expressing DC-SIGN, and the levels of proinflammatory cytokines in the kidney tissues improved correspondingly. The results also indicated that VitC could suppress the DC-SIGN expression in the tubular epithelial cells induced by HS and alleviate the inflammation and functional injury in the kidney.
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http://dx.doi.org/10.4103/0366-6999.185868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960965PMC
July 2016

Prospective observational study to compare oral topical metronidazole versus 0.2% chlorhexidine gluconate to prevent nosocomial pneumonia.

Am J Infect Control 2016 10 14;44(10):1116-1122. Epub 2016 Jun 14.

Emergency Department & Emergency Intensive Care Unit, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Background: Nosocomial pneumonia is one of the most common health care-associated infections in intensive care units (ICUs) worldwide, attributing to high morbidity and mortality. Our study aim is to investigate the effectiveness of oral hygiene with 0.2% chlorhexidine gluconate (CHX) and 0.08% metronidazole (MDE) influencing the microbiologic epidemiology and incidence of nonintubation pneumonia (NIP) and ventilator-associated pneumonia (VAP).

Methods: Patients who stayed >48 hours in the emergency ICU between 2008 and 2012 were enrolled and provided oral hygiene by swabbing with 0.08% MDE twice daily until discharge or death during the first year (period M), whereas CHX was applied during the following 3 years (period C). The incidence and microbiologic epidemiology of NIP and VAP were studied.

Results: There were 873 patients enrolled. There were 44 episodes of NIP and 25 episodes of VAP that occurred among 212 patients in period M, and 84 episodes of NIP and 49 episodes of VAP occurred among 661 patients in period C. Overall, the rate of NIP and VAP decreased year by year. Acinetobacter baumannii was the most frequently identified bacteria for NIP (22.9%) and VAP (25.3%), with an annual ascent. Few changes were observed on bacteria distribution for NIP and VAP.

Conclusions: Oral hygiene with CHX, having reduced the incidence of nosocomial pneumonia among critical ill patients, suggests a benefit of oral hygiene in decreasing the incidence of nosocomial pneumonia, including VAP in ICUs, but not bacterial epidemiology.
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http://dx.doi.org/10.1016/j.ajic.2016.03.054DOI Listing
October 2016

Effect of S100A12 and soluble receptor for advanced glycation end products on the occurrence of severe acute pancreatitis.

J Dig Dis 2016 Jul;17(7):475-82

Department of Emergency Intensive Care Unit, Shanghai, China.

Objective: To assess whether serum levels of S100A12 and soluble receptor for advanced glycation end products (sRAGE) could predict the severity of acute pancreatitis (AP).

Methods: We conducted a non-interventional pilot study, including 74 AP patients and 28 healthy volunteers serving as controls. AP patients were further divided into the mild (MAP, n = 22), moderately severe (MSAP, n = 30) and severe (SAP, n = 22) groups. Peripheral blood samples were collected within 72 h after the onset of AP for the determination of S100A12, sRAGE and C-reactive protein (CRP) levels. The acute physiology and chronic health evaluation II (APACHE II) score, Balthazar computed tomography severity index (CTSI) were calculated at admission.

Results: S100A12 and sRAGE levels in SAP patient were significantly higher than in controls, MAP and MSAP patients. The receiver operating characteristic (ROC) curve analysis demonstrated the predictive ability of S100A12 [sensitivity 91%, specificity 81%, the area under the ROC curve AUROC 0.9047] and sRAGE (sensitivity 57%, specificity 100%, AUROC 0.8304) for evaluating the severity of AP. S100A12 and sRAGE were correlated with APACHE II and CTSI but not with CRP. This combination of new and traditional indicators had higher accuracy than traditional indicators alone. Specifically, S100A12 and sRAGE were positively correlated with the type of organ failure (respiratory and renal failure) and might distinguish transient from persistent organ failure at admission.

Conclusion: S100A12 and sRAGE could be used as efficient biomarkers for the early identification of SAP.
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http://dx.doi.org/10.1111/1751-2980.12364DOI Listing
July 2016

Quantitative hepatitis B surface antigen combined with hepatitis B e antigen as sustained virological response predictors during extended therapy with Peginterferon alfa-2a for hepatitis B e antigen-positive chronic hepatitis B.

J Clin Virol 2015 Nov 9;72:88-94. Epub 2015 Oct 9.

Research Unit of Clinical Virology, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China; Translational Medicine Research Center, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People's Republic of China. Electronic address:

Background: The best strategy for chronic hepatitis B patients with poor response to 48 weeks of Peginterferon-based therapy has been controversial and the predictive value of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels for determining the sustained virological response (SVR) of these patients is uncertain.

Objectives: To optimize management of these patients and evaluate the use of these serobiomarkers to predict SVR.

Study Design: Eighty-one patients with an unsatisfactory response after 48 weeks of Peginterferon-based therapy were treated with extended Peginterferon therapy with or without nucleo(s) tide analogues (NAs), for a total of 96 weeks of Peginterferon treatment. HBsAg, HBeAg and HBV DNA levels were measured serially during the treatment and follow-up.

Results And Conclusions: Twenty-six of 81 patients (32.1%) attained SVR during the 72-week follow-up. The SVR rate was not statistically different between groups receiving 1-year prolongation of Peginterferon with or without NAs. The serum HBsAg cut-off of 1800IU/mL at week 48 had area under curve (AUC) of 0.727, and the serum HBsAg cut-off of 1500IU/mL, combined with HBeAg loss at week 72, had AUC of 0.753 to predict SVR during the follow-up. In conclusion, extended treatment with Peginterferon with or without NAs for patients with unsatisfactory response after 48 weeks of Peginterferon-based therapy is a promising strategy to achieve SVR, and quantitative serum HBsAg at week 48 and HBsAg level combined with HBeAg loss at week 72 of therapy can predict SVR to prolongation therapy with Peginterferon.
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http://dx.doi.org/10.1016/j.jcv.2015.09.012DOI Listing
November 2015

Characterization of Full-Length Genomes of Hepatitis B Virus Quasispecies in Sera of Patients at Different Phases of Infection.

J Clin Microbiol 2015 Jul 29;53(7):2203-14. Epub 2015 Apr 29.

Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Translational Medicine Research Centre, Ruijin Hospital North, Shanghai Jiaotong University, School of Medicine, Shanghai, China

Hepatitis B virus (HBV) infection results in different clinical presentation due to different levels of immune response. Our study aimed to characterize HBV full-length genome quasispecies (QS) in patients with different phases of infection to better understand its pathogenesis. Forty treatment-naive HBV-infected patients were enrolled, including 10 cases of acute hepatitis B (AHB), 9 cases of immunotolerant (IT) HBV carriers, 11 cases of chronic hepatitis B (CHB), and 10 cases of acute-on-chronic liver failure (ACLF). The present study was conducted by clone-based sequencing. QS heterogeneity within each open reading frame was calculated. The mutation frequency index (MFI) and amino acid variations within the large HBsAg, HBcAg, and HBxAg regions were analyzed based on the different infection phases. In total, 606 HBV full-length sequences were obtained. HBV QS had higher heterogeneity in ACLF and CHB than that in IT among chronically infected individuals. AHB patients had the lower QS heterogeneity at onset than those with chronic infection. ACLF patients had the highest frequency of mutations in the core promoter and precore region. A triple mutation (A1762T/G1764A/G1896A) was observed more frequently in genotype C than in genotype B. The MFI indicated that specific peptides of the studied regions had more frequent mutations in ACLF. Furthermore, several amino acid variations, known as T- and B-cell epitopes, were potentially associated with the immunoactive phase of infection. More HBV genome mutations and deletions were observed in patients with more severe diseases, particularly in specific regions of the core and preS regions, the clinical significance and mechanism of which need to be further investigated.
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http://dx.doi.org/10.1128/JCM.00068-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4473231PMC
July 2015

Epidemiology, species distribution and outcome of nosocomial Candida spp. bloodstream infection in Shanghai.

BMC Infect Dis 2014 May 6;14:241. Epub 2014 May 6.

Emergency Department & Emergency Intensive Care Unit, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No, 197 Ruijin Er Road, Shanghai 200025, China.

Background: Yeasts, mostly Candida, are important causes of bloodstream infections (BSI), responsible for significant mortality and morbidity among hospitalized patients. The epidemiology and species distribution vary from different regions. The goals of this study were to report the current epidemiology of Candida BSI in a Shanghai Teaching Hospital and estimate the impact of appropriate antifungal therapy on the outcome.

Methods: From January 2008 to December 2012, all consecutive patients who developed Candida BSI at Ruijin University Hospital were enrolled. Underlying diseases, clinical severity, species distribution, antifungal therapy and its impact on the outcome were analyzed.

Results: A total of 121 episodes of Candida BSI were identified, with an incidence of 0.32 episodes/1,000 admissions (0.21 in 2008 and 0.42 in 2012) The proportion of candidemia caused by non-albicans species (62.8%), including C. parapsilosis (19.8%), C. tropicalis (14.9%), C. glabrata (7.4%), C. guilliermondii (5.8%), C. sake (5.0%) was higher than that of candidemia caused by C. albicans (37.2%). The overall crude 28-day mortality was 28.1% and significantly reduced with appropriate empiric antifungal therapy administered within 5 days (P = 0.006). Advanced age (OR 1.04; P = 0.014), neutropenia < 500/mm3 (OR 17.44; P < 0.001) were independent risk factors for 28-day mortality, while appropriate empiric antifungal therapy (OR 0.369; P = 0.035) was protective against 28-day mortality.

Conclusion: The epidemiology of candidemia in Shanghai differed from that observed in Western countries. Appropriate empiric antifungal therapy influenced the short-term survival.
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http://dx.doi.org/10.1186/1471-2334-14-241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033490PMC
May 2014

Current ciprofloxacin usage in children hospitalized in a referral hospital in Paris.

BMC Infect Dis 2013 May 27;13:245. Epub 2013 May 27.

Service des Maladies Infectieuses et Tropicales & Centre d'Infectiologie Necker-Pasteur, Université Paris Descartes, Hôpital Necker-Enfants Malades, Paris, France.

Background: Fluoroquinolones are used with increasing frequency in children with a major risk of increasing the emergence of FQ resistance. FQ use has expanded off-label for primary antibacterial prophylaxis or treatment of infections in immune-compromised children and life-threatening multi-resistant bacteria infections. Here we assessed the prescriptions of ciprofloxacin in a pediatric cohort and their appropriateness.

Methods: A monocenter audit of ciprofloxacin prescription was conducted for six months in a University hospital in Paris. Infected site, bacteriological findings and indication, were evaluated in children receiving ciprofloxacin in hospital independently by 3 infectious diseases consultants and 1 hospital pharmacist.

Results: Ninety-eight ciprofloxacin prescriptions in children, among which 52 (53.1%) were oral and 46 (46.9%) parenteral, were collected. 45 children had an underlying condition, cystic fibrosis (CF) (21) or an innate or acquired immune deficiency (24). Among CF patients, the most frequent indication was a broncho-pulmonary Pseudomonas aeruginosa infection (20). In non-CF patient, the major indications were broncho-pulmonary (25), urinary (8), intra-abdominal (7), operative site infection (5) and bloodstream/catheter (2/4) infection. 62.2% were microbiologically documented. Twenty-three (23.4%) were considered "mandatory", 48 (49.0%) "alternative" and 27 (27.6%) "unjustified".

Conclusion: In our university hospital, only 23.4% of fluoroquinolones prescriptions were mandatory in children, especially in Pseudomonas aeruginosa healthcare associated infection. Looking to the ecological risk of fluoroquinolones and the increase consumption in children population we think that a control program should be developed to control FQ use in children. It could be done with the help of an antimicrobial stewardship team.
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http://dx.doi.org/10.1186/1471-2334-13-245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668209PMC
May 2013

Polymorphisms of microsomal triglyceride transfer protein in different hepatitis B virus-infected patients.

World J Gastroenterol 2008 Sep;14(35):5454-60

Department of Infectious Diseases, Ruijin Hospital, 197 Ruijin Er Road, Shanghai, China.

Aim: To identify the two polymorphisms of microsomal triglyceride transfer protein (MTP) gene in the Chinese population and to explore their correlation with both hepatitis B virus (HBV) self-limited infection and persistent infection.

Methods: A total of 316 subjects with self-limited HBV infection and 316 patients with persistent HBV infection (195 subjects without familial history), matched with age and sex, from the Chinese Han population were enrolled in this study. Polymorphisms of MTP at the promoter region -493 and at H297Q were determined by the allele specific polymerase chain reaction (PCR).

Results: The ratio of males to females was 2.13:1 for each group and the average age in the self-limited and chronic infection groups was 38.36 and 38.28 years, respectively. None of the allelic distributions deviated significantly from that predicted by the Hardy-Weinberg equilibrium. There was a linkage disequilibrium between H297Q and -493G/T (D' = 0.77). As the c2 test was used, the genotype distribution of MTP-493G/T demonstrated a significant difference between the self-limited infection group and the entire chronic group or the chronic patients with no family history (c2 = 8.543, P = 0.015 and c2 = 7.199, P = 0.019). The allele distribution at the MTP-493 position also demonstrated a significant difference between the study groups without family history (c2 = 6.212, P = 0.013). The T allele emerged as a possible protective factor which may influence the outcomes of HBV infection (OR: 0.59; 95% CI: 0.389-0.897).

Conclusion: The polymorphism of the MTP gene, T allele at -493, may be involved in determining the HBV infection outcomes, of which the mechanism needs to be further investigated.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744166PMC
http://dx.doi.org/10.3748/wjg.14.5454DOI Listing
September 2008

[A comparison between serum myoglobin and acute physiology and chronic health evaluation II score in the evaluation of disease severity and prognosis in critically ill patients].

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2008 Sep;20(9):538-41

Emergency Department of Ruijin Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.

Objective: To determine the clinical significance of serum myoglobin (Mb) in the evaluation of severity and prognosis of non-cardiogenic critically ill patients by comparing with acute physiology and chronic health evaluation II (APACHE II) score.

Methods: One hundred and thirty patients admitted consecutively to emergency intensive care unit (EICU) from April to December in 2005 were enrolled for the study. Determination of serum Mb content, routine serum biochemical tests and APACHE II scoring were performed simultaneously. The serum Mb was measured with the use of chemoluminescence and solid-chromatography. All the patients were followed up till recovery/discharge or death.

Results: APACHE II score, white blood cell count and mortality were significantly different between the two groups classified by the content of serum Mb [Mb < 140 microg/L (76 patients) and Mb > or = 140 microg/L (55 patients)]. When Mb rose, diseases aggravated, APACHE II score and mortality went up (both P < 0.01). APACHE II score, Mb and neutrophil were remarkably higher in the death group (45 patients) than the recovery group (86 patients, all P < 0.01). Stepwise Cox Regression showed that Mb and APACHE II score were the parameters that related to the survival rate, while Mb was the main option. When Mb > 500 microg/L, the mortality rate was 82% (23/28); when APACHE II score > 20, the mortality rate was 85% (23/27); the morality rate went up to 95% (19/20) in the patients with Mb > 500 microg/L and APACHE II score > 20, suggesting that a combination of Mb determination and APACHE II score would raise the accuracy of evaluation of the prognosis of critically ill patients.

Conclusion: Compares with APACHE II score for evaluation of critical illness, Mb can also be considered as a significant biomarker to evaluate the seriousness of the ailment in the critically ill and to judge the effect of the treatment.Therefore, it could be used as a prospective and meaningful biomarker for a quick evaluation of the disease severity in the ICU, so it is worth for further study.
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September 2008

[Association of polymorphism of 2'-5' oligoadenylate synthetase 1 gene with the susceptibility of hepatitis B virus infection and IFN-alpha treatment response].

Zhonghua Gan Zang Bing Za Zhi 2007 Oct;15(10):779-80

Department of Infectious Diseases, Affiliated Ruiji Hospital, Medical College, Shanghai Jiaotong University, Shanghai 200025, China.

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October 2007

Morganella morganii pericarditis 3 years after allogenic bone marrow transplantation for mantle cell lymphoma.

J Infect 2006 Nov 29;53(5):e223-5. Epub 2006 Mar 29.

Department of Infectious Diseases and Tropical Medicine, Necker-Enfants Malades Hospital, René Descartes Paris-5 University Medical School, Paris, France.

We report herein a case of Morganella morganii-associated acute purulent pericarditis that developed 3 years after allogenic bone marrow transplantation. The patient was successfully treated with surgical drainage and cefotaxime for 6 weeks. Splenectomy and immunosuppression for chronic GVH-D are likely to have favored the development of this rare infectious complication after BMT. M. morganii should be added to the list of bacteria causing purulent pericarditis, especially in immunocompromised hosts.
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http://dx.doi.org/10.1016/j.jinf.2006.02.001DOI Listing
November 2006
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