Major advances in respiratory medicine in China

Respiratory disease is the term for diseases of the respiratory system. These diseases range from mild and self-limiting such as the common cold to life-threatening such as bacterial pneumonia or pulmonary embolism. They are common and important causes of illness and death. In the US, people suffer 1 billion colds per year. One out of 7 people in the UK are affected by some kinds of chronic lung diseases, most commonly chronic obstructive pulmonary disease （COPD） and asthma. Respiratory disease accounts for over 10% of hospitalizations and over 16% of deaths in Canada.     

Positive end expiratory pressure titrated by transpulmonary pressure improved oxygenation and respiratory mechanics in acute respiratory distress syndrome patients with intra-abdominal hypertension

Background Intra-abdominal hypertension （IAH） is common in acute respiratory distress syndrome （ARDS） patients and when resulting in decrease of chest wall compliance will weaken the effect of positive end expiratory pressure （PEEP）. We investigated the effect of PEEP titrated by transpulmonary pressure （Ptp） on oxygenation and respiratory mechanics in ARDS patients with IAH compared with PEEP titrated by ARDSnet protocol. Methods ARDS patients admitted to the intensive care unit （ICU） of the Zhongda Hospital were enrolled. Patients were ventilated with volume control mode with tidal volume of 6 ml/kg under two different PEEP levels titrated by Ptp method and ARDSnet protocol. Respiratory mechanics, gas exchange and haemodynamics were measured after 30 minutes of ventilation in each round. IAH was defined as intra-abdominal pressure of 12 mmHg or more, Results Seven ARDS patients with IAH and 8 ARDS patients without IAH were enrolled. PEEP titrated by Ptp were significant higher than PEEP titrated by ARDSnet protocol in both ARDS patients with IAH （（17.3±2.6）cmH20 vs. （6.3±1.6） cmH2O and without IAH （（9.5±2.1） cmH2O vs. （7.8±1.9） cmH2O）. Arterial pressure of O2/fraction of inspired oxygen （PaO2/ FiO2） was much higher under PEEP titrated by Ptp when compared with PEEP titrated by ARDSnet protocol in ARDS patients with IAH （（27.2±4.0） cmHg vs. （20.9± 5.0） cmHg. But no significant difference of PaO2/FiO2 between the two methods was found in ARDS patients without IAH. In ARDS patients with IAH, static compliance of lung and respiratory system were higher under PEEP titrated by Ptp than by ARDSnet protocol. In ARDS patients with IAH, central venous pressure （CVP） was higher during PEEP titrated by Ptp than by ARDSnet protocol. Conclusion Positive end expiratory pressure titrated by transpulmonary pressure was higher than PEEP titrated by ARDSnet protocol and improved oxygenation and respiratory mechanics in ARDS patients with IAH.     

A （H1N1） Influenza Pneumonia with Acute Disseminated Encephalomyelitis： A Case Report

INTRODUCTION
A 56-year-old Chinese female patient with A （H1N1） influenza pneumonia accompanied by acute disseminated encephalomyelitis （ADEM） of the Central Nervous System （CNS） is described in this article. The patient had typical clinical manifestation, and the diagnosis was reached after MRI and other examinations. From this case, we can conclude that the virus of A （H1N1） influenza can infect CNS, and we should pay more attention to patients of A （H1N1） influenza pneumonia with neurological complications.     

Detection of cytokine expression patterns in the peripheral blood of patients with acute leukemia by antibody microarray analysis

The cytokines of acute leukemia （AL） patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission （CR） for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia （AML） and acute lymphoblastic leukemia （ALL）. In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.     

Expressions of miR-22 and miR-135a in acute pancreatitis

This study examined the expressions of miR-22 and miR-135a in rats with acute edematous pancreatitis （AEP） and their target genes in order to shed light on the involvement of miR-22 and miR-135a in the pathogenesis of acute pancreatitis （AP）. The in vivo model of AEP was established by introperitoneal injection of L-arginine （150 mg/kg） in rats. The miRNA microarray analysis was used to detect the differential expression of miRNAs in pancreatic tissue in AEP and normal rats. The in vitro AEP model was established by inducing the rat pancreatic acinar cell line （AR42J） with 50 ng/mL re- combinant rat TNF-ct. Real-time quantitative RT-PCR was employed to detect the expression of miR-22 and miR-135a in AR42J cells. Lentiviruses carrying the miRNA mimic and anti-miRNA oligonucleotide （AMO） of miR-22 and miR-135a were transfected into the AR42J cells. The AR42J cells transfected with vehicle served as control. Western blotting was used to measure the expression of activated cas- pase3 and flow cytometry analysis to detect the apoptosis of AR42J cells. Targets of miR-22 and miR-135a were predicted by using TargetScan, miRanda, and TarBase. Luciferase reporter assay and quantitative real-time RT-PCR were performed to confirm whether ErbB3 and Ptk2 were the target gene of miR-22 and miR-135a, respectively. The results showed that the expression levels of miR-22 and miR-135a were obviously increased in AEP group compared with the control group in in-vivo and in-vitro models. The expression levels of miR-22 and miR-135a were elevated conspicuously and the expression levels of their target genes were reduced significantly in AR42J cells transfected with Ienti- viruses carrying the miRNA mimic. The apoptosis rate was much higher in the TNF-ct-induced cells than in non-treated cells. The AR42J cells transfected with miRNA AMOs expressed lower level of miR-22 and miR-135a and had lower apoptosis rate, but the expression levels of ErbB3 and Ptk2 were increased obviously. It was concluded that the expression levels of miR-22 and miR-135a were elevated in AEP. Up-regulating the expression of miR-22 and miR-135a may promote the apoptosis of pancreatic acinar cells by repressing ErbB3 and Ptk2 expression in AEP.     

Predicting value of serum soluble ST2 and interleukin-33 for risk stratification and prognosis in patients with acute myocardial infarction

Background Acute myocardial infarction （AMI） is a common cardiac emergency with high mortality.Serum soluble ST2 （sST2） is a new emerging biomarker of cardiac diseases.The present study is to investigate the predictive value of sST2 and interleukin-33 （IL-33） for risk stratification and prognosis in patients with AMI.Methods Fifty-nine patients with AMI,whose chief complaint was chest pain or dyspnea,were selected for our study.Physical examination,chest radiograph,electrocardiograph （ECG）,biomarkers of myocardial infarction,NT-proBNP,echocardiography and other relevant examinations were performed to confirm the diagnosis of AMI.Thirty-six healthy people were chosen as the control group.Serum samples from these subjects （patients within 24 hours after acute attack） were collected and the levels of sST2 and IL-33 were assayed by enzyme-linked immuno-sorbent assay （ELISA） kit.The follow-up was performed on the 7th day,28th day,3rd month and 6th month after acute attack.According to the follow-up results we defined the end of observation as recurrence of AMI or any causes of death.Results Median sST2 level of the control group was 9.38ng/ml and that of AMI patients was 29.06ng/ml.Compared with the control group,sST2 expression in the AMI group was significantly different （P〈0.001）.In contrast,the IL-33 level showed no significant difference between the two groups.Serum sST2 was a predictive factor independent of other variables and may provide complementary information to NT-proBNP or GRACE risk score.IL-33 had no relationship to recurrence of AMI.Both sST2 and the IL-33/sST2 ratio were correlated with the 6-month prognosis; areas under the ROC curve were 0.938 and 0.920 respectively.Conclusions Early in the course （〈24 hours） of AMI,sST2 usually increases markedly.The increase of sST2 has an independent predictive value for the prognosis in AMI patients and provides complementary information to NT-proBNP or GRACE risk score.The IL-33/sST2 ratio correlates with the 6-month prognosis of AMI patients.However,there is no significant relationship between IL-33 and the prognosis of AMI patients.     

The percentage of peripheral blood blasts on day 7 of induction chemotherapy predicts response to therapy and survival in patients with acute myeloid leukemia

Background Rapid clearance of peripheral blood blasts （PBBs） predicts complete remission （CR） and survival in patients with acute myeloid leukemia （AML）.We aimed to explore the correlation between induction therapy response,outcome,and the PBB percentage.Methods Forty-six consecutive patients with de novo AML （excluding acute promyelocytic leukemia） were enrolled in this study.Flow cytometry was performed to identify cells with a leukemia-associated aberrant immunophenotype in the initial bone marrow aspirate and in peripheral blood on day 7 of induction therapy.Results The PBB percentage on day 7 （D7PBBP） was significantly lower in patients who achieved CR （0.03% （0.0%,0.45%）） than in those who did not （10.85% （1.13%,19.38%）; u =-3.92,P 〈0.001）.The CR rate was significantly higher among patients with a D7PBBP of 〈0.945% （84.62%,22/26） than among those with a D7PBBP of 〉0.945% （25.0%,5/20;Х^2 =16.571,P 〈0.001）.D7PBBP was significantly correlated with overall survival （OS; r=-0.437,P=0.003） and relapsefree survival （RFS; r=-0.388,P=0.007）.OS and RFS were significantly higher in patients with a D7PBBP of 〈0.43% than in those with a D7PBBP of 〉0.43% （P 〈0.001 and P=0.039,respectively）.D7PBBP was also found to be an independent prognostic indicator in multivariate analysis for both OS （P=-0.036） and RFS （P=0.035）.Conclusion D7PBBP may be an important risk factor for the achievement of complete remission,for overall survival,and for relapse-free survival.     

Severe crush syndrome complicated with acute pancreatitis: a case report and review of the literatures

Earthquake is one of the most catastrophic natural disasters. As we know, crush syndrome is the secondmost frequent cause of mortality after the direct impact of trauma.1-3 It is a serious clinical case that develops among casualties of earthquakes or other catastrophic events that may also result in a variety of ensuing uncommon complications. Cases of crush syndrome complicated with acute pancreatitis （AP） following the earthquakes are seldom reported.     

Isolated non-compaction of ventricular myocardium in a victim of the Wenchuan earthquake with crush syndrome and acute renal failure

Non-compaction of the ventricular myocardium （NVM） is a rare congenital genetic heart defect that was initially reported 17 years ago by means of autopsy; few cases have been published since then. It has been classified as the primary inherited cardiomyopathy by the American Heart Association Scientific Statement in 2006 under contemporary definitions and classification of cardiomyopathies. It is caused by an arrested development of muscle fiber compaction, a process that normally takes place dunng early embryogenesls, which is characterized by numerous sinusoids or trabeculae that are excessive in number and abnormal in prominence and by deep intratrabecular recesses covered by endothelium that exhibits continuity with ventricular endocardium. It usually involves one and/or more segments of the left ventricle, while the clinical manifestations are highly variable,     

Relapse of acute lymphoblastic leukemia in the pancreas after allogeneic bone marrow transplantation

The occurrence of metastatic lesions in the pancreas of patients with cancer, including hematological cancers,is uncommon （1.6%-37.5%） and of these, the majority of patients will have widespread disease.1-7 Isolated potentially resectable pancreatic metastases are rarely seen. Resection of metastatic tumors of the pancreas has been reported, but its role in improving survival rates or quality of life is not clear.7,8 However,     

Chinese children′s respiratory diseases in 60 years

This year marks the 60th anniversary of the founding of the People＇s Republic of China. On this occasion,it is worthy to recall the past and look towards the future in order to do a better job in research and control of children＇s respiratory diseases.     

Pre-hospital care-seeking in patients with acute myocardial infarction and subsequent quality of care in Beijing

Background Cumulative evidence demonstrates that primary percutaneous coronary intervention（PCI）is a mperfusion strategy for ST-elevation myocardial Infarction（STEMI）.This study was undertaken to evaluate the pre-hospital care-seeking pathway and subsequent care quality in patients with STEMI in the Beijing health care system,which offers patients a choice between seeking care in a small community hospital（SH group）or a large hospital（LH group）.Methods Between January 1 and December 31,2006, a cross-sectional and multicenter survey was conducted in 11 hospitals qualified as tertiary centers in Beijing and included consecutive patients with STEMI admitted within 24 hours after onset of symptoms.Results Among the 566 patients interviewed,28.3%first arnved at a small community hospitaI and were transferred to large hospitals with the ability to perform primary PCI.The median total pre-hospital delay in the SH group（n=160）was significantly longer than in the LH group（n=406）（225 vs.120 minutes,P〈0.001）.Multivariate analysis showed that interpreting symptoms to non-cardiac origin（OR,1.996;95%CI： 1.264-3.155）,absence of history of myocardial infarction（OR,1.595;95%CI：1.086-3.347）,non-health insuranca coverage（OR,1.931;95%Cl：1.079-3.012）and absence of sense of impending doom （OR,4.367;95%CI：1.279-1 4.925） were independent predictors for choosing small hospitals.After adjusting for demographics and medical history,patients in the SH group were 1.698 times（95% CI： 1.1 82-3.661） less likely to receive primary PCI compared with those in the LH group. Conclusions Above one fourth of the STEMI patients in Beijing experienced inter-hospital transfer.Factors including symptoms interpretation,symptoms,history of myocardial infarcUon,and insurance coverage were associated with the patients＇pre-hospital care-seeking pathway.The patients who were transferred had longer pre-hospital delays and were less Iikely to receive primary PCI.     

Antithrombin-III without concomitant heparin improves endotoxin-induced acute lung injury rats by inhibiting the activation of mitogen-activated protein kinase

Background Antithrombin-Ⅲ （AT-Ⅲ）, the major inhibitor of thrombin in plasma, also has anti-inflammation property and might have positive effect on sepsis. The present study aimed to investigate the effects of AT-Ⅲ on inflammatory reaction and pulmonary protection in endotoxin-induced acute lung injury （ALI） rat. Methods Sixty male Sprague-Dawley rats were randomly assigned equally to normal control group, ALl group, AT-Ⅲ treatment group, AT-Ⅲ＋heparin treatment group, and heparin treatment group. The pulmonary vascular permeability index （PVPI） was measured by single nuclide tracer technique. The activity of AT-Ⅲ in plasma was determined by the method of synthetic chromogenic substrata. Tumor necrosis factor-a （TNF-a） and interleukin-6 （IL-6） levels in serum were determined by enzyme-linked immunosorbent assay. The expressions of lung tissue mitogen-activated protein kinases （ERK1/2, P38 and JNK MAPK） were determined by Western blotting. Results Rats had significantly improved lung histopathology in the AT-Ⅲ treatment group and heparin treatment group compared with the ALl group, The PVPI of the ALl group was 0.38±0.04, significantly higher than that of the normal control group （0.20±0.02, P 〈0.01）, AT-Ⅲ treatment group （0.30±0.04, P 〈0.01） and heparin treatment group （0.28±0.04, P 〈0.01） respectively. There were no significant differences of PVPI in the ALl group and AT-Ⅲ＋heparin treatment group. The activity of AT-Ⅲ in plasma in the ALl group was （76±8）%, significantly lower than that of the normal control group （（96±11）%, P 〈0.05） and AT-Ⅲ treatment group （（105±17）%, P 〈0.05） respectively. The serum levels of TNF-α and I L-6 of the ALl group were （2.770±0.373） μg/L and （1.615±0.128） ng/ml respectively, significantly higher than those of the normal control group （0.506±0.093） μg/L and （0.233±0.047） ng/ml respectively, all P 〈0.01）, AT-Ⅲ treatment group （（1.774±0.218） pg/L and （1.140±0145） ng/ml respectively, all P 〈0.01） and heparin treatment group （（1.924±0.349） μg/L and （1.223±0.127） ng/ml respectively, all P 〈0.01）. The lung tissue levels of phospho-ERK1/2 and phospho-P38 MAPK expressions were markedly higher in the ALl group than in the normal control group, AT-Ⅲ treatment group and heparin treatment group respectively. Conclusions AT-Ⅲ without concomitant heparin inhibited the activation of ERK1/2 and P38 MAPK, down-regulated the levels of downstream cytokines TNF-a and IL-6, relieved endothelial permeability, and improved the ALl in endotoxin-induced rats. It might be helpful to administrate AT-Ⅲ alone, not with concomitant heparin, to those patients with ALl and sepsis.     

Combined treatment with erythropoietin and granulocyte colony-stimulating factor enhances neovascularization and improves cardiac function after myocardial infarction

Background Erythropoietin （EPO） and granulocyte colony-stimulating factor （G-CSF） are both potential novel therapeutics for use after myocardial infarction （MI）.However,their underlying mechanisms remain unclear and the efficacy of monotherapy with EPO or G-CSF is also controversial.Therefore,we investigated the effects of combined treatment with EPO and G-CSF on neovascularization and cardiac function in post-infarction rats and explored the potential mechanisms.Methods Four groups of rats were used：control （saline injection after MI,i.h.）,EPO （a single dose of 5 000 IU/kg after MI,i.h.）,G-CSF （a dose of 50 μg· kg-1· d-1 for 5 days after MI,i.h.）,and both EPO and G-CSF （EPO＋G-CSF,using the same regiment as above）.Cardiac function was assessed by echocardiography before and 1 day,7 days,14 days and 21 days after MI.CD34＋/Flk-1＋ cells in the peripheral blood were evaluated by flow cytometry before and 3 days,5 days and 7 days after MI.The infarct area and angiogenesis in the peri-infarct area were analyzed.The mRNA and protein expression of vascular endothelial growth factor （VEGF） and stromal-derived factor-1α （SDF-1α） in the peri-infarct area were detected by real-time quantitative RT-PCR and Western blotting.Results Compared with the control and monotherapy groups,the EPO＋G-CSF group had significantly increased CD34＋/ Flk-1＋ endothelial progenitor calls （EPCs）in the peripheral blood （P ＜0.05）,up-regulated VEGF and SDF-1α levels in the peri-infarct region （P ＜0.05）,enhanced capillary density （P ＜0.05）,reduced infarct size （P ＜0.05） and improved cardiac structure and function （P ＜0.05）.G-CSF alone did not dramatically increase EPCs in the peripheral blood,enhance capillary density in the peri-infarct area or reduce infarct size compared with the control group.Conclusions Combined treatment with EPO and G-CSF increased EPCs mobilization,up-regulated VEGF and SDF-1α levels in the post-infarction microenvironment,subsequently enhanced neovascularization in the peri-infarct region and reduced infarct size.All factors contributed to its beneficial effects on cardiac function in post-infarction rats.     

Effects of resolvin D1 on inflammatory responses and oxidative stress of lipopolysaccharide-induced acute lung injury in mice

Background A variety of inflammatory mediators and effector cells participate together in acute lung injury,and lead to secondary injury that is due to an inflammatory cascade and secondary diffuse lung parenchyma injury.Inflammation is associated with an oxidative stress reaction,which is produced in the development of airway inflammation,and which has positive feedback on inflammation itself.Resolvin D1 can reduce the infiltration of neutrophils,regulate cytokine levels and reduce the inflammation reaction,and thereby promote the resolution of inflammation.The purpose of this study is to investigate the effects of resolvin D1 on an inflammatory response and oxidative stress during lipopolysaccharide （LPS）-induced acute lung injury.Methods LPS （3 mg/kg） was used to induce the acute lung injury model.Pretreatment resolvin D1 （100 ng/mouse） was given to mice 30 minutes before inducing acute lung injury.Mice were observed at 6 hours,12 hours,1 day,2 days,3 days,4 days and 7 days after LPS was administrated,then they were humanely sacrificed.We collected bronchoalveolar lavage fluid （BALF） and the lung tissues for further analysis.Paraffin section and HE staining of the lung tissues were made for histopathology observations.Parts of the lung tissues were evaluated for wet-to-dry （W/D） weight ratio.tumor necrosis factor （TNF）-α,inter leukin （IL）-1β,IL-10 and myeloperoxidase （MPO） were detected by enzyme-linked immunosorbent assay （ELISA）.A lipid peroxidation malondialdehyde （MDA） assay kit was used to detect MDA.A total superoxide dismutase assay kit with WST-1 was used to analyze superoxide dismutase （SOD）.We determined the apoptosis of neutrophils by Flow Cytometry.A real-time quantitative PCR Detecting System detected the expression of mRNA for heme oxygenase （HO）-1.Results Pretreatment with resolvin D1 reduced the pathological damage in the lung,decreased the recruitment of neutrophils and stimulated their apoptosis.It markedly decreased the expressions of TNF-α,IL-1β and increased the expressions of IL-10,and decreased the production of MDA and increased the expressions of SOD.The mRNA expression of HO-1 was also significantly increased.Conclusions Resolvin D1 displays potent anti-inflammatory actions by regulating cytokines,inhibiting aberrant neutrophil recruitment and stimulating apoptosis of neutrophils.Resolvin D1 can also relieve the injury due to oxidative stress.The mechanisms might be related to increase HO-1 expression.     

Primary hyperparathyroidism presenting as acute gallstone pancreatitis

Primary hyperparathyroidism （PHPT） is a generalized disorder of calcium metabolism resulting from an abnormally high level of serum calcium and an increased level of parathormone （PTH）. 1,2 Traditionally, symptomatic PHPT patients present with a variety of disorders including fatigue, amyotrophy, memory impairment, emotional instability, hallucination, irritation, loss of consciousness, abdominal distention, nausea,     

Mechanical ventilation in acute respiratory distress syndrome: past, present and future

Acute respiratory distress syndrome （ARDS） is a life threatening respiratory failure due to lung injury from a variety of precipitants.Mechanical ventilation （MV） is the foundation in the supportive management of patients with ARDS.1 However,it is associated with several complications,such as increased risk of pneumonia and development of lung injury.The improved understanding of ARDS and complications from MV has been considered important in designing lung-protective ventilatory strategies aimed at attenuating or preventing organ dysfunction and improving outcomes.     

Effect of surfactant protein A on lipopolysaccharide-induced tumor necrosis factor-α expression in human proximal tubular epithelial cells

Background Surfactant protein A （SP-A） contributes to the regulation of sepsis-induced acute lung injury.In a previous study,we demonstrated the expression and localization of SP-A in the kidneys.The present study evaluated the effect of SP-A on lipopolysaccharide （LPS）-induced tumor necrosis factor-α （TNF-α） expression and its underlying mechanisms in the human renal tubular epithelial （HK-2） cells.Methods Indirect immunofiuorescence assay was used to detect SP-A distribution and expression in HK-2 cells.HK-2 cells were treated with various concentrations of LPS （0,0.1,1,2,5,and 10 mg/L） for 8 hours and with 5 mg/L LPS for different times （0,2,4,8,16,and 24 hours） to determine the effects of LPS on SP-A and TNF-α expression.Then,HK-2 cells were transfected with SP-A siRNA to analyze nuclear factor κB （NF-κB） P65 and TNF-α expression of HK-2 cells after LPS-treatment.Results Indirect immunofluorescence assay revealed that SP-A is localized to the membrane and cytoplasm of HK-2 cells.Interestingly,SP-A1/SP-A2 and TNF-α expression were found to be significantly increased in HK-2 cells upon LPS treatment.Transfection of LPS-treated HK-2 cells with SP-A siRNA resulted in significant increases in the levels of NF-κB P65 protein and TNF-α mRNA and protein compared to those in non-transfected LPS-treated HK-2 cells.Conclusion SP-A plays an important role in protecting cells against sepsis-induced acute kidney injury by inhibiting NF-κB activity to modulate LPS-induced increase in TNF-α expression.     

Feasibility of using 6F angiographic catheters for primary percutaneous coronary intervention in patients with acute myocardial infarction

The transradial access has been used for percutaneous coronary intervention （PCI） for more than 10 years. Many studies have confirmed several advantages of a radial route over the traditional transfemoral approach, some of which include a decreased incidence of access site complications, an earlier ambulation after the procedure which helps make patients more comfortable after the procedure.4-SHowever, the radial artery is easier to spasm as it is smaller than the femoral artery. This kind of phenomenon often happens when shifting from angiographic catheters to guiding catheters.     

Neurological deterioration in the acute phase of minor ischemic stroke is an independent predictor of poor outcomes at 1 year： results from the China National Stroke Registry （CNSR）

Background The risk of clinical deterioration still exists in the acute phase despite the fact that patients with minor stroke may display less severe symptoms.The impact of this clinical deterioration...