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Objective@#To investigate the role of endoplasmic reticulum stress (ERS) in rats with acute respiratory distress syndrome (ARDS) related right ventricular dysfunction and the protective effect of sodium 4-phenylbutyrate (4-PBA) on right ventricle.@*Methods@#Sixty male Spragne-Dawley (SD) rats were randomly divided into control group (CON group), lipopolysaccharide (LPS) model group, 4-PBA prevention group and 4-PBA treatment group, with 15 rats in each group. ARDS rat model was established by intratracheal instillation of LPS 10 mg/kg after tracheotomy; CON group was given the same amount of saline. 4-PBA prevention group and 4-PBA treatment group were given 4-PBA 500 mg/kg intragastric administration 2 hours before and after LPS respectively. Echocardiography was performed 12 hours after treatment to evaluate the right ventricular function. Then, the rats were sacrificed by bloodletting, and the serum and right ventricular tissue were harvested. The histopathological changes of myocardial were observed by hematoxylin-eosin (HE) staining, the levels of tumor necrosis factor-α(TNF-α), interleukins (IL-1β and IL-6) in serum and myocardial were detected by enzyme linked immunosorbent assay (ELISA), and Western Blot was used to detect the expression of the marker proteins of ERS in myocardial, including glucose regulatory protein 78 (GRP78), C/EBP cyclic adenosine phosphate reaction primitive binding transcription factor homologous protein (CHOP), caspase-12 and caspase-3.@*Results@#Compared with the CON group, the echocardiography showed pulmonary artery maximum pressure gradient (PAmaxPG), pulmonary artery acceleration time (PAAT), tricuspid annular plane systolic excursion (TAPSE) in LPS model group were significantly decreased, and right ventricular end-diastolic excursion (RVDd) was significantly increased, and the levels of TNF-α, IL-1β and IL-6 in serum and myocardial, as well as the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly increased. Compared with LPS model group, TAPSE of 4-PBA preventive and treatment groups were significantly increased (mm: 3.08±0.65, 2.96±0.61 vs. 2.48±0.45), RVDd were significantly decreased (mm: 3.67±0.58, 3.60±0.61 vs. 4.18±0.71), the levels of TNF-α, IL-1β and IL-6 in serum and myocardial were significantly decreased [TNF-α (ng/L): 187.98±18.98, 176.08±17.98 vs. 332.00±19.90 in serum, 135.06±19.00, 132.78±17.00 vs. 155.00±20.00 in myocardial; IL-1β(ng/L): 12.07±2.98, 11.05±2.41 vs. 24.06±4.01 in serum, 19.89±2.80, 21.06±2.80 vs. 26.00±2.60 in myocardial; IL-6 (ng/L): 42.98±7.90, 34.05±6.09 vs. 89.80±10.07 in serum, 129.45±25.00, 127.08±26.06 vs. 145.77±23.00 in myocardial]; the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly decreased (GRP78/GAPDH: 0.090±0.070, 0.103±0.060 vs. 0.167±0.090, CHOP/GAPDH: 0.109±0.090, 0.090±0.080 vs. 0.186±0.090, caspase-12/GAPDH: 0.769±0.230, 0.799±0.210 vs. 1.040±0.350, caspase-3/GAPDH: 0.391±0.060, 0.401±0.054 vs. 0.603±0.340), with statistically significant differences (all P < 0.05). There were no significant differences in each indexes between 4-PBA prevention group and 4-PBA treatment group (all P > 0.05).@*Conclusions@#ERS is involved in ARDS-related right ventricular dysfunction. 4-PBA can protect the right ventricular function of ARDS rats by inhibiting ERS and alleviating inflammation, and the preventive and therapeutic effects of 4-PBA are similar.
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Objective To investigate the role of endoplasmic reticulum stress (ERS) in rats with acute respiratory distress syndrome (ARDS) related right ventricular dysfunction and the protective effect of sodium 4-phenylbutyrate (4-PBA) on right ventricle. Methods Sixty male Spragne-Dawley (SD) rats were randomly divided into control group (CON group), lipopolysaccharide (LPS) model group, 4-PBA prevention group and 4-PBA treatment group, with 15 rats in each group. ARDS rat model was established by intratracheal instillation of LPS 10 mg/kg after tracheotomy; CON group was given the same amount of saline. 4-PBA prevention group and 4-PBA treatment group were given 4-PBA 500 mg/kg intragastric administration 2 hours before and after LPS respectively. Echocardiography was performed 12 hours after treatment to evaluate the right ventricular function. Then, the rats were sacrificed by bloodletting, and the serum and right ventricular tissue were harvested. The histopathological changes of myocardial were observed by hematoxylin-eosin (HE) staining, the levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1β and IL-6) in serum and myocardial were detected by enzyme linked immunosorbent assay (ELISA), and Western Blot was used to detect the expression of the marker proteins of ERS in myocardial, including glucose regulatory protein 78 (GRP78), C/EBP cyclic adenosine phosphate reaction primitive binding transcription factor homologous protein (CHOP), caspase-12 and caspase-3. Results Compared with the CON group, the echocardiography showed pulmonary artery maximum pressure gradient (PAmaxPG), pulmonary artery acceleration time (PAAT), tricuspid annular plane systolic excursion (TAPSE) in LPS model group were significantly decreased, and right ventricular end-diastolic excursion (RVDd) was significantly increased, and the levels of TNF-α, IL-1β and IL-6 in serum and myocardial, as well as the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly increased. Compared with LPS model group, TAPSE of 4-PBA preventive and treatment groups were significantly increased (mm: 3.08±0.65, 2.96±0.61 vs. 2.48±0.45), RVDd were significantly decreased (mm: 3.67±0.58, 3.60±0.61 vs. 4.18±0.71), the levels of TNF-α, IL-1β and IL-6 in serum and myocardial were significantly decreased [TNF-α (ng/L): 187.98±18.98, 176.08±17.98 vs. 332.00±19.90 in serum, 135.06±19.00, 132.78±17.00 vs. 155.00±20.00 in myocardial; IL-1β(ng/L): 12.07±2.98, 11.05±2.41 vs. 24.06±4.01 in serum, 19.89±2.80, 21.06±2.80 vs. 26.00±2.60 in myocardial; IL-6 (ng/L): 42.98±7.90, 34.05±6.09 vs. 89.80±10.07 in serum, 129.45±25.00, 127.08±26.06 vs. 145.77±23.00 in myocardial]; the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly decreased (GRP78/GAPDH: 0.090±0.070, 0.103±0.060 vs. 0.167±0.090, CHOP/GAPDH: 0.109±0.090, 0.090±0.080 vs. 0.186±0.090, caspase-12/GAPDH: 0.769±0.230, 0.799±0.210 vs. 1.040±0.350, caspase-3/GAPDH: 0.391±0.060, 0.401±0.054 vs. 0.603±0.340), with statistically significant differences (all P < 0.05). There were no significant differences in each indexes between 4-PBA prevention group and 4-PBA treatment group (all P > 0.05). Conclusions ERS is involved in ARDS-related right ventricular dysfunction. 4-PBA can protect the right ventricular function of ARDS rats by inhibiting ERS and alleviating inflammation, and the preventive and therapeutic effects of 4-PBA are similar.
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Objective To investigate the role of endoplasmic reticulum stress (ERS) in rats with acute respiratory distress syndrome (ARDS) related right ventricular dysfunction and the protective effect of sodium 4-phenylbutyrate (4-PBA) on right ventricle. Methods Sixty male Spragne-Dawley (SD) rats were randomly divided into control group (CON group), lipopolysaccharide (LPS) model group, 4-PBA prevention group and 4-PBA treatment group, with 15 rats in each group. ARDS rat model was established by intratracheal instillation of LPS 10 mg/kg after tracheotomy; CON group was given the same amount of saline. 4-PBA prevention group and 4-PBA treatment group were given 4-PBA 500 mg/kg intragastric administration 2 hours before and after LPS respectively. Echocardiography was performed 12 hours after treatment to evaluate the right ventricular function. Then, the rats were sacrificed by bloodletting, and the serum and right ventricular tissue were harvested. The histopathological changes of myocardial were observed by hematoxylin-eosin (HE) staining, the levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1β and IL-6) in serum and myocardial were detected by enzyme linked immunosorbent assay (ELISA), and Western Blot was used to detect the expression of the marker proteins of ERS in myocardial, including glucose regulatory protein 78 (GRP78), C/EBP cyclic adenosine phosphate reaction primitive binding transcription factor homologous protein (CHOP), caspase-12 and caspase-3. Results Compared with the CON group, the echocardiography showed pulmonary artery maximum pressure gradient (PAmaxPG), pulmonary artery acceleration time (PAAT), tricuspid annular plane systolic excursion (TAPSE) in LPS model group were significantly decreased, and right ventricular end-diastolic excursion (RVDd) was significantly increased, and the levels of TNF-α, IL-1β and IL-6 in serum and myocardial, as well as the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly increased. Compared with LPS model group, TAPSE of 4-PBA preventive and treatment groups were significantly increased (mm: 3.08±0.65, 2.96±0.61 vs. 2.48±0.45), RVDd were significantly decreased (mm: 3.67±0.58, 3.60±0.61 vs. 4.18±0.71), the levels of TNF-α, IL-1β and IL-6 in serum and myocardial were significantly decreased [TNF-α (ng/L): 187.98±18.98, 176.08±17.98 vs. 332.00±19.90 in serum, 135.06±19.00, 132.78±17.00 vs. 155.00±20.00 in myocardial; IL-1β(ng/L): 12.07±2.98, 11.05±2.41 vs. 24.06±4.01 in serum, 19.89±2.80, 21.06±2.80 vs. 26.00±2.60 in myocardial; IL-6 (ng/L): 42.98±7.90, 34.05±6.09 vs. 89.80±10.07 in serum, 129.45±25.00, 127.08±26.06 vs. 145.77±23.00 in myocardial]; the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly decreased (GRP78/GAPDH: 0.090±0.070, 0.103±0.060 vs. 0.167±0.090, CHOP/GAPDH: 0.109±0.090, 0.090±0.080 vs. 0.186±0.090, caspase-12/GAPDH: 0.769±0.230, 0.799±0.210 vs. 1.040±0.350, caspase-3/GAPDH: 0.391±0.060, 0.401±0.054 vs. 0.603±0.340), with statistically significant differences (all P < 0.05). There were no significant differences in each indexes between 4-PBA prevention group and 4-PBA treatment group (all P > 0.05). Conclusions ERS is involved in ARDS-related right ventricular dysfunction. 4-PBA can protect the right ventricular function of ARDS rats by inhibiting ERS and alleviating inflammation, and the preventive and therapeutic effects of 4-PBA are similar.
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Objective To discuss the diagnostic value of a diagnostic strategy combining D-dimer and aortic dissection detection risk score (ADDRS) for patients with acute aortic dissection (AAD). Methods The clinical data of 750 patients with suspected AAD in emergency department of Zhongda Hospital Affiliated to Southeast University from January 2016 to January 2018 were retrospectively analyzed, including medical history, gender, age, chief complaint, physical examination, diagnostic imaging data and D-dimer levels on admission. ADDRS = 0 was defined as low risk group, ADDRS = 1 as medium risk group, ADDRS≤1 as non-high risk group,whereas ADDRS > 1 as high risk group. The clinical characteristics of AAD and non-AAD patients, ADDRS, D-dimer, and the diagnostic ability of D-dimer (the cutoff value of 500 μg/L) for AAD in different risk groups were observed. Results AAD was diagnosed in 79 of 750 (10.53%) patients. Of the 256 (34.13%) patients in low risk group, 5 patients were diagnosed with AAD. The medium risk group had 337 (44.93%) patients, including 44 cases with AAD. The high risk group had 157 (20.93%) patients, including 30 cases with AAD. In AAD patients, the proportion of male and hypertension, the incidence of ADDRS risk markers (including abrupt onset of pain, severe pain intensity, ripping or tearing pain, pulse deficit or systolic blood pressure differential of upper limb, focal neurological deficit, recent aortic manipulation, known thoracic aortic aneurysm) and the D-dimer levels in AAD group were significantly higher than those of non-AAD patients [male: 82.28% (65/79) vs. 59.76% (401/671), hypertension: 81.01% (64/79) vs. 41.43% (278/671), abrupt onset of pain: 78.48% (62/79) vs. 39.94% (268/671), severe pain intensity: 78.48% (62/79) vs. 50.52% (339/671), ripping or tearing pain: 32.91% (26/79) vs. 0.75% (5/671), pulse deficit or systolic blood pressure differential of upper limb: 15.19% (12/79) vs. 0.15% (1/671), focal neurological deficit: 7.59% (6/79) vs. 1.64% (11/671), recent aortic manipulation: 6.33% (5/79) vs. 0.30% (2/671), known thoracic aortic aneurysm: 15.19% (12/79) vs. 0.30% (2/671), D-dimer (μg/L): 1 160 (588, 3 340) vs 135 (56, 478), all P < 0.05], the proportion of diabetics was significantly lower than that of non-AAD patients [7.59% (6/79) vs. 18.78% (126/671), P < 0.05]. The positive predictive values of D-dimer for AAD diagnosis in the low risk group and the non-high-risk groups (including low and medium risk groups) were lower than that in the high risk group (8.62%, 26.32% vs. 40.91%), the negative predictive values of D-dimer were higher in the low risk group and non-high-risk groups than that in the high risk group (100.00%, 99.05% vs. 96.70%), missed diagnosis rates were higher than that in high risk group (0, 0.95%, vs. 3.30%). Conclusion In the high risk group, D-dimer≥500 μg/L is helpful for diagnosis of AAD; and in low risk group or non-high-risk group, D-dimer < 500 μg/L can efficiently and accurately exclude AAD.
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Our previous works disclosed the contributing role of macrophage migration inhibitory factor (MIF) and dopaminergic inhibition by lysine dimethyltransferase G9a/Glp complex in peripheral nerve injury-induced hypersensitivity. We herein propose that the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity by interacting with and suppressing the descending dopaminergic system. The lumbar spinal cord (L-SC) and ventral tegmental area (VTA) are two major locations with significant upregulation of MIF after chronic constriction injury (CCI) of the sciatic nerve, and they display time-dependent changes, along with a behavioral trajectory. Correspondingly, dopamine (DA) content shows the reverse characteristic change to MIF with a time-dependent curve in post-surgical behavior. The levels of both MIF and DA are reversed by the MIF tautomerase inhibitor ISO-1, and a negative relationship exists between MIF and DA. The reversed role of ISO-1 also affects tyrosine hydroxylase expression. Furthermore, CCI induces Th promoter CpG site methylation in the L-SC and VTA areas, and this effect could be abated by ISO-1 administration. G9a/SUV39H1 and H3K9me2/H3K9me3 enrichment within the Th promoter region following CCI in the L-SC and VTA was also decreased by ISO-1. In cultured dopaminergic neurons, rMIF enhanced the recruitment of G9a and SUV39H1, followed by an increase in H3K9me2/H3K9me3. These molecular changes correspondingly exhibited alterations in Th promoter CpG site methylation and pain behaviors. In summary, MIF functions as a braking factor in curbing dopaminergic descending inhibition in peripheral nerve injury-induced hypersensitivity by mediating Th gene methylation through G9a/SUV39H1-associated H3K9 methylation.
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Objective To explore the effect of acute respiratory distress syndrome (ARDS) induced by endotoxin on the right ventricular function in rats. Methods Sixty male Sprague-Dawley (SD) rats were randomly divided into normal saline (NS) control group and lipopolysaccharide (LPS) model group with 30 rats in each group. The rat model of ARDS was reproduced by intratracheal instillation of LPS 10 mg/kg after tracheotomy, and the rats in NS control group was intratracheally given the same volume of NS instead of LPS. The survival of rats in each group was observed. Right ventricular function was evaluated by echocardiography at 6 hours and 12 hours after instillation of LPS or NS respectively. Then the rats were sacrificed by bloodletting, and the right heart and lung tissue were harvested. The lung wet/dry weight (W/D) ratio was assessed. The pathological changes in cardiopulmonary tissue in rats were observed with hematoxylin and eosin (HE) strain, and the pathological score of lung injury was calculated. Results There was no animal death in NS control group. In LPS model group, there were 3 rats dead at 6 hours, and 4 dead at 12 hours. The pathological manifestations of lung injury were found at 6 hours after instillation of LPS, and the marked pathological changes of ARDS, such as atelectasis and hyaline membranes were observed at 12 hours. There was no obvious abnormality in the lung tissue of the NS control group. Compared with the NS control group, the 12-hour lung W/D ratio and the lung injury pathological score in the LPS model group were significantly increased (lung W/D ratio:7.69±1.02 vs. 4.14±0.48, lung injury pathological score: 8.26±2.12 vs. 1.32±0.94, both P < 0.01). Echocardiography showed that the right heart function of rats was significantly abnormal with the prolongation of LPS induction time, which showed that pulmonary arterial diameter (PAD) and right ventricular diastolic diameter (RVDd) were increased, maximum blood flow velocity of pulmonary artery (PAVmax), maximum pulmonary artery pressure gradient (PAmaxPG),pulmonary artery acceleration time (PAAT) and tricuspid annular plane systolic excursion (TAPSE) were decreased, with significant differences at 12 hours as compared with those of NS normal group [PAD (mm): 2.84±0.31 vs. 2.11±0.37, RVDd (mm): 4.18±0.71 vs. 3.17±0.40, PAVmax (mm/s): 704.00±145.13 vs. 809.59±120.48, PAmaxPG (mmHg, 1 mmHg = 0.133 kPa): 2.07±0.88 vs. 2.73±0.76, PAAT (ms): 23.80±4.87 vs. 30.01±3.02, TAPSE (mm): 2.48±0.45 vs. 3.56±0.40, all P < 0.01]. Pathological examination showed that the cardiac tissue in the LPS model group showed disorder of myocardial cells and scattered inflammatory cells at 6 hours, and cardiomyocyte degeneration, structural destruction and inflammatory cells were found at 12 hours. Conclusion ARDS induced by instillation of LPS at 12 hours causes right ventricular dysfunction in rats.
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A total of 109 in patients with crayfish-related rhabdomyolysis were enrolled in our hospital from July to August 2016,including 31.2％(34/109)males and 68.8％ (75/109)females.The number of home-cooked crayfish accounted for 60.6％ (66/109).Main symptom was back pain 96.3％ (105/109).The misdiagnosis rate was 15.6％ (17/109).On day 1,2,3 after admission and the day before discharge,serum creatine kinase were 1 175(446,2 258)IU/L,3 710(2 137,8 875)IU/L,1 899(1 063,4595)IU/L and 317 (152,532)IU/L,respectively(P＜0.001).Serum myoglobin were (603±484)μg/L,(313±284)μg/L,(104±74)μg/L and (55 ± 20)μg/L,respectively(F=39.1,P＜0.001).Females were more susceptible to cra.crayfish-related rhabdomyolysis.Home-cooked crayfish is prone to induce rhabdomyolysis and easily to be misdiagnosed.Creatine kinase and myoglobin showed characteristic dynamic changes.
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Objective To investigate the epidemiology characteristics of crawfish related rhabdomyolysis (RM) in Nanjing, 2016.Methods Outpatient and inpatient electronic medical system of 21 hospitals in Nanjing during 2016 were retrospectively searched, and all the patients diagnosed with RM were selected. The patients with none crayfish-related RM was excluded. The epidemiology characteristics were depicted. The geographic information system (GIS) was used to collect, manage and analyze the spatial data, to visualize it, to analyze the spatial distribution features of the disease, and to explore the cause of disease prediction. GeoDa 1.8 software was used to analyze the global and local spatial auto-correlation.Results A total of 1183 patients with crawfish related RM were initially screened, excluding 59 patients with RM caused by trauma, severe exercise, heat stroke, myositis, poisoning, drugs, and genetic diseases, and 1124 patients were enrolled. The proportion of men was 36.48% (410/1124) with an incidence of 12.54/100 thousands; while of women was 63.52% (714/1124) with an incidence of 21.86/100 thousands. The median age at onset was 34 (28, 43) years. From July to August, the incidence of crawfish related RM was the highest, accounting for 96.53% of the total number of cases. The top four incidence areas were Pukou (41.54/100 thousands), Jianye (25.94/100 thousands), Qixia (25.73/100 thousands), Gulou (25.04/100 thousands), all of which were adjacent to the Yangtze River. Global spatial autocorrelation analysis showed: MoranI = 0.427,Z = 2.646,P = 0.003, suggesting that the crawfish related RM had positive spatial autocorrelation. The results showed that the spatial structure of crawfish related RM existed in Nanjing in 2016. Local spatial autocorrelation analysis showed that the high-high concentration areas were Pukou, Jianye and Liuhe. The incidences of above three areas which were the Nanjing section of the lower reaches of the Yangtze River flowed through the region and surrounding areas were higher than the overall incidence of Nanjing.Conclusion The prevalence of crawfish related RM in Nanjing during 2016 had an obvious region-concentrated character and global spatial autocorrelation with the high prevalent regions mainly concentrated in the urban areas adjacent to the Yangtze River.
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Objective To evaluate the diagnostic accuracy of Streptocuccus pneumoniae urinary antigen test (SpUAT) in patients with community acquired Streptocuccus pneumoniae pneumoniae (SPP). Methods The clinical studies relating SpUAT diagnostic accuracy for community acquired Streptocuccus pneumoniae infection were searched via computer and manual screening of Chinese databases including China National Knowledge Internet (CNKI), China Biology Medicine disc, China Technical Journal Full-text Database, and Wanfang Database as well as English databases such as PubMed, EBSCO, Elsevier Science, Ovid Technologies, and Springer. Data were extracted according to appropriate inclusion and exclusion criteria and analyzed with Meta-disc 1.4 and Stata 12.0 software. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio as well as diagnostic odds ratio (DOR) were calculated, and summary receiver operating characteristic curve (SROC) was plotted and area under SROC (AUC) was calculated to analyze the diagnostic accuracy of SpUAT for adult community acquired SPP. Results A total of 15 studies enrolling 6 866 patients were included, all of which with a quality assessment of diagnostic accuracy studies (QUADAS) score not lower than 10, indicating a high study quality. Random effect model was applied owing to non-threshold effect associated heterogeneity. It was shown by Meta analysis that compared with routine pathogen diagnosis (hemoculture, sputum smears, sputum culture and trachea and bronchus attractive culture), the pooled sensitivity, pooled specificity, pooled positive likelihood ratio, and pooled negative likelihood ratio was 73% [95% confidence interval (95%CI) = 71%-76%,] 91% (95%CI = 90%-92%), 6.97 (95%CI = 4.13-11.77), and 0.30 (95%CI = 0.26-0.34), respectively, pooled DOR was 24.34 (95%CI = 13.14-45.11), and AUC of SROC was 0.8051±0.0362. It was indicated by heterogeneity test that experiment design (prospective or retrospective), sample sizes (lower than 200 or higher than or equal to 200), reference test (fewer than 3 or more than or equal to 3 test methods), or literature language (Hispanic or non-Hispanic) had no effect on study heterogeneity, indicating certain other unknown factors may be involved. Funnel plot suggested that 15 involved studies uniformly distributed along the two sides of regression line, indicating no publication bias. Conclusions The use of SpUAT for the diagnosis of adult community acquired SPP has a moderate sensitivity and high specificity. Although the overall accuracy of SpUAT diagnosis is relatively high, there is significant heterogeneity among the studies, so more high-quality studies are needed.
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Objective To determine the effect of enhanced hand hygiene on the morbidity of ventilator-associated pneumonia (VAP).Methods Clinical studies which were related to enhanced hand cleansing to the risk of VAP,which were published between July 1992 and June 2013 in English or Chinese were retrieved via computer and manual screening.Data were extracted according to appropriate inclusion and exclusion criteria and analyzed with RevMan 5.0 software.Results A total of 6 studies,all of which were performed with well controlled protocol,involving 28 461 mechanical ventilator days and 32 428 mechanical ventilator days were analyzed.The morbidity of VAP was 39.5 days per 1 000 mechanical ventilator days and 19.5 days per 1 000 mechanical ventilator days before and after enhanced hand cleaning,respectively.The methods of enhancing hand hygiene included feasible hand hygiene apparatus,long-term education,supervision and feedback,as well as increased hand cleaning compliance.All 6 eligible studies reported that enhanced hand washing lowered the risk of VAP,with risk reduction ranging from 29.8％ to 65.5％ with a mean reduction value of 50.6％.Meta analysis showed that enhanced hand cleaning could protect patients from VAP with odds ratio (OR) varying from 1.43 to 5.82 [pooled OR=2.23,95％ confidence interval (95％CI) 1.62-3.07,P＜0.000 01].It was showed in funnel chart that bias in the published articles was not significant.Conclusions Enhanced hand hygiene has an effect of prevention of VAP morbidity and is associated with lowered morbidity of VAP.However,the reliability of this conclusion is questionable because of poor quality of these studies.