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BackgroundParavertebral block (PVB) is the most recognized regional anesthesia technique after thoracic epidural anesthesia for postoperative analgesia in thoracic and breast surgery. Erector spinae plane block (ESPB) is a recently discovered blocking technique, and it has evidenced excellent postoperative analgesia for breast and thoracic surgery with fewer adverse reactions. However, there are controversies about the postoperative analgesic effects of the two analgesic techniques.ObjectiveTo assess the analgesic effects of PVB versus ESPB in postoperative thoracic and breast surgery.MethodsWe systematically searched PubMed, Cochrane Library, EMBASE, Web of Science, and ScienceDirect databases up to April 5, 2021. The primary outcome was postoperative pain scores. Secondary outcomes included: opioid consumption, additional analgesia, postoperative nausea and vomiting (PONV) 24 hours post-operation, and the time required for completing block procedure. This study was registered in PROSPERO, number CRD42021246160.ResultsAfter screening relevant, full-text articles, ten randomized controlled trials (RCTs) that met the inclusion criteria were retrieved for this meta-analysis. Six studies involved thoracic surgery patients, and four included breast surgery patients. Thoracic surgery studies included all of the outcomes involved in this meta-analysis while breast surgery did not report pain scores at movement and additional analgesia in 24 hours post-operation. For thoracic surgery, PVB resulted in significant reduction in the following pain scores: 0-1 hours (MD = -0.79, 95% CI: -1.54 to -0.03, P = 0.04), 4-6 hours (MD = -0.31, 95% CI: -0.57 to -0.05, P = 0.02), and 24 hours (MD = -0.42, 95% CI: -0.81 to -0.02, P = 0.04) at rest; significant reduction in pain scores at 4-6 hours (MD = -0.47, 95% CI: -0.93 to -0.01, P = 0.04), 8-12 hours (MD = -1.09, 95% CI: -2.13 to -0.04, P = 0.04), and 24 hours (MD = -0.31, 95% CI: -0.57 to -0.06, P = 0.01) at movement. Moreover, the opioid consumption at 24 hours post-operation (MD = -2.74, 95% CI: -5.41 to -0.07, P = 0.04) and the incidence of additional analgesia in 24 hours of the postoperative course (RR: 0.53, 95% CI: 0.29 to 0.97, P = 0.04) were significantly lower in the PVB group than in the ESPB group for thoracic surgery. However, no significant differences were found in pain scores at rest at various time points postoperatively, and opioid consumption at 24 hours post-operation for breast surgery. The time required for completing block procedure was longer in the PVB group than in the ESPB group for thoracic and breast surgery, and the incidence of PONV between the two groups showed no significant difference.ConclusionThe postoperative analgesic effects of PVB versus ESPB are distinguished by the surgical site. For thoracic surgery, the postoperative analgesic effect of PVB is better than that of ESPB. For breast surgery, the postoperative analgesic effects of PVB and ESPB are similar.

[This corrects the article DOI: 10.1371/journal.pone.0191172.].

AIMS:Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS:From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS:We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

Myocardial Infarction (MI) has become a major cause of morbidity and mortality in China, but little is known about the prevalence of guideline-recommended cardiovascular medications after MI events over the last two decades. This systematic review and meta-analysis aims to summarize cardiovascular medication use between 1995-2015 and to assess factors in associated with the trends in cardiovascular medications.A systematic search was conducted in four databases (Pubmed, Embase, CENTRAL, and CNKI) to obtain observational studies published between 1995 and 2015, reporting on the use of cardiovascular medications in China. Risk of bias of individual studies was appraised and selected studies were pooled for estimated prevalence of cardiovascular medication. Prevalence of cardiovascular medication use for 1995 and 2015 was estimated by random effects meta-regression model.From 13,940 identified publications, 35 studies, comprising 28,000 patients, were included. The pooled prevalence for aspirin, beta-blockers, statins, ACE-Inhibitors, ACE-Inhibitor/ARBs and nitrates was 92% [95% confidence interval (CI): 0.89-0.95], 63% (95% CI: 0.57-0.69), 72% (95% CI: 0.60-0.82), 49% (95% CI: 0.41-0.57), 59% (95% CI: 0.48-0.69) and 79% (95% CI: 0.74-0.91), respectively. A significant increase in beta-blocker and statin use and a decrease of nitrate use was observed over time. The estimated prevalence of beta-blockers, statins, and nitrates was 78%, 91.1%, and 59.3% in 2015, compared to 32%, 17% and 96% in 1995, respectively.Cardiovascular medication use after MI is far from optimal in Chinese patients, even though the prevalence of use increased over the period 1995-2015. With a rapidly increasing number of MI patients in China, a comprehensive strategy on secondary prevention is warranted.PROSPERO (CRD42015025246).

Large outbreaks of hand, foot, and mouth disease (HFMD) have repeatedly occurred in mainland of China since 2007. In this study, we investigated the epidemiological and aetiological characteristics of HFMD in Shijiazhuang City, one of the biggest northern cities of China. A total of 57,173 clinical HFMD cases, including 911 severe and 32 fatal cases, were reported in Shijiazhuang City during 2009-2012. The disease incidence peaked during March-July, with a small increase in the number of cases observed in November of each year. Seventeen potential HFMD-causing enterovirus serotypes were detected, with the most frequent serotypes being EV-A71 and CV-A16. CV-A10 was also a frequently detected causative serotype, and was associated with the second largest number of severe HFMD cases, following EV-A71. Phylogenetic analysis revealed that all EV-A71, CV-A16 and CV-A10 strains from Shijiazhuang City had co-evolved and co-circulated with those from other Chinese provinces. Our findings underscore the need for enhanced surveillance and molecular detection for HFMD, and suggest that EV-A71 vaccination may be an effective intervention strategy for HFMD prevention and vaccines against CV-A10 and CV-A16 are also urgently needed.

We demonstrated in experimental studies that hypercholesterolaemia enhances the proliferation of haematopoietic stem cells and the subsequent differentiation to neutrophils, whereas HDL-cholesterol inhibits these processes. To translate our experimental findings to clinical practice, we investigated in Chinese type-2 diabetic patients and in Flemish non-diabetic people the independent and joint associations of insulin resistance with markers of dyslipidaemia and inflammation, while looking for consistency between ethnicities and across the spectrum of insulin resistance.We studied 798 Chinese patients with type-2 diabetes (53.6% women; mean age, 60.6 years) admitted to a tertiary referral centre and 1060 white Flemish (50.5%; 51.1 years) randomly recruited in Northern Belgium. Fasting insulin resistance (HOMA-IR) was derived from C-peptide in Chinese and from insulin in Flemish using the Homeostasis Model of Assessment algorithm. In multivariable-adjusted analyses, HOMA-IR was regressed on triglycerides, HDL-cholesterol and neutrophil count.In Chinese patients, the percentage changes in HOMA-IR associated with triglycerides, HDL-cholesterol and neutrophils (per 1-SD increment) amounted to 8.1 (95% confidence interval, 3.0 to 13.4; p = 0.0015), -8.7 (-13.0 to -4.2; p = 0.0002) and 5.6 (1.0 to 10.4; p = 0.017). In non-diabetic Flemish, the corresponding estimates were 11.7 (8.3 to 15.1; p

This multicenter, randomized, placebo-controlled study evaluated the efficacy and side effects of parecoxib during patient-controlled epidural analgesia (PCEA) after abdominal hysterectomy.A total of 240 patients who were scheduled for elective abdominal hysterectomy under combined spinal-epidural anesthesia received PCEA plus postoperative intravenous parecoxib 40 mg or saline every 12 h for 48 h after an initial preoperative dose of parecoxib 40 mg or saline. An epidural loading dose of a mixture of 6 mL of 0.25% ropivacaine and 2 mg morphine was administered 30 min before the end of surgery, and PCEA was initiated using 1.25 mg/mL ropivacaine and 0.05 mg/mL morphine with a 2-mL/h background infusion and 2-mL bolus with a 15-min lockout. The primary end point of this study was the quantification of the PCEA-sparing effect of parecoxib.Demographic data were similar between the two groups. Patients in the parecoxib group received significantly fewer self-administrated boluses (0 (0, 3) vs. 7 (2, 15), P < 0.001) and less epidural morphine (5.01 ± 0.44 vs. 5.95 ± 1.29 mg, P < 0.001) but experienced greater pain relief compared with the control group (P < 0.001). Patient global satisfaction was higher in the parecoxib group than the control group (P < 0.001). Length of hospitalization (9.50 ± 2.1, 95% CI 9.12~9.88 vs. 10.41 ± 2.6, 95% CI 9.95~10.87, P = 0.003) and postoperative vomiting (17% vs. 29%, P < 0.05) were also reduced in the parecoxib group. There were no serious adverse effects in either group.Our data suggest that adjunctive parecoxib during PCEA following abdominal hysterectomy is safe and efficacious in reducing pain, requirements of epidural analgesics, and side effects.ClinicalTrials.gov (NCT01566669).

OBJECTIVES:To estimate the effects of achieving China's national goals for dietary salt (NaCl) reduction or implementing culturally-tailored dietary salt restriction strategies on cardiovascular disease (CVD) prevention. METHODS:The CVD Policy Model was used to project blood pressure lowering and subsequent downstream prevented CVD that could be achieved by population-wide salt restriction in China. Outcomes were annual CVD events prevented, relative reductions in rates of CVD incidence and mortality, quality-adjusted life-years (QALYs) gained, and CVD treatment costs saved. RESULTS:Reducing mean dietary salt intake to 9.0 g/day gradually over 10 years could prevent approximately 197 000 incident annual CVD events [95% uncertainty interval (UI): 173 000-219 000], reduce annual CVD mortality by approximately 2.5% (2.2-2.8%), gain 303 000 annual QALYs (278 000-329 000), and save approximately 1.4 billion international dollars (Int$) in annual CVD costs (Int$; 1.2-1.6 billion). Reducing mean salt intake to 6.0 g/day could approximately double these benefits. Implementing cooking salt-restriction spoons could prevent 183 000 fewer incident CVD cases (153 000-215 000) and avoid Int$1.4 billion in CVD treatment costs annually (1.2-1.7 billion). Implementing a cooking salt substitute strategy could lead to approximately three times the health benefits of the salt-restriction spoon program. More than three-quarters of benefits from any dietary salt reduction strategy would be realized in hypertensive adults. CONCLUSION:China could derive substantial health gains from implementation of population-wide dietary salt reduction policies. Most health benefits from any dietary salt reduction program would be realized in adults with hypertension.

The recycling of livestock manure in cropping systems is considered to enhance soil fertility and crop productivity. However, there have been no systematic long-term studies of the effects of manure application on soil and crop macro- and micro-nutrients, heavy metals, and crop yields in China, despite their great importance for sustainable crop production and food safety. Thus, we conducted field experiments in a typical cereal crop production area of the North China Plain to investigate the effects of compost manure application rates on wheat yield, as well as on the macro-/micro-nutrients and heavy metals contents of soil and wheat. We found that compost application increased the soil total N and the available K, Fe, Zn, and Mn concentrations, whereas the available P in soil was not affected, and the available Cu decreased. In general, compost application had no significant effects on the grain yield, biomass, and harvest index of winter wheat. However, during 2012 and 2013, the N concentration decreased by 9% and 18% in straw, and by 16% and 12% in grain, respectively. With compost application, the straw P concentration only increased in 2012 but the grain P generally increased, while the straw K concentration tended to decrease and the grain K concentration increased in 2013. Compost application generally increased the Fe and Zn concentrations in straw and grain, whereas the Cu and Mn concentrations decreased significantly compared with the control. The heavy metal concentrations increased at some compost application rates, but they were still within the safe range. The balances of the macro-and micro-nutrients indicated that the removal of nutrients by wheat was compensated for by the addition of compost, whereas the level of N decreased without the application of compost. The daily intake levels of micronutrients via the consumption of wheat grain were still lower than the recommended levels when sheep manure compost was applied, except for that of Mn.

Amyloid-β (Aβ), the major component of neuritic plaques in Alzheimer's disease (AD), is derived from sequential proteolytic cleavage of amyloid protein precursor (APP) by secretases. In this study, we found that cystatin C (CysC), a natural cysteine protease inhibitor, is able to reduce Aβ40 secretion in human brain microvascular endothelial cells (HBMEC). The CysC-induced Aβ40 reduction was caused by degradation of β-secretase BACE1 through the ubiquitin/proteasome pathway. In contrast, we found that CysC promoted secretion of soluble APPα indicating the activated non-amyloidogenic processing of APP in HBMEC. Further results revealed that α-secretase ADAM10, which was transcriptionally upregulated in response to CysC, was required for the CysC-induced sAPPα secretion. Knockdown of SIRT1 abolished CysC-triggered ADAM10 upregulation and sAPPα production. Taken together, our results demonstrated that exogenously applied CysC can direct amyloidogenic APP processing to non-amyloidgenic pathway in brain endothelial cells, mediated by proteasomal degradation of BACE1 and SIRT1-mediated ADAM10 upregulation. Our study unveils previously unrecognized protective role of CysC in APP processing.

Many studies aimed at investigating bone repair have been conducted through animal models in recent years. However, limitations do exist in these models due to varying regeneration potential among different animal species. Even using the same animal, big differences exist in the size of critical size defects (CSD) involving the same region. This study aimed to investigate the standardization of radial bone defect models in rabbits and further establish more reliable CSD data. A total of 40 6-month-old New Zealand white rabbits of clean grade totaling 80 radial bones were prepared for bone defect models, according to the principle of randomization. Five different sizes (1.0, 1.2, 1.4, 1.7 and 2.0 cm) of complete periosteal defects were introduced under anesthesia. At 12 weeks postoperatively, with the gradual increase in defect size, the grades of bone growth were significantly decreased in all 5 groups. X-ray, CT scans and H&E staining of the 1.4, 1.7, and 2.0-cm groups showed lower grades of bone growth than that of the 1.0 and 1.2-cm groups respectively (P < 0.05). Using rabbit radial defect model involving 6-month-old healthy New Zealand white rabbits, this study indicates that in order to be critical sized, defects must be greater than 1.4 cm.

Hyperimmunoglobulinemia is frequently observed in patients with chronic liver diseases. However, the exact mechanism underlying the high level of antibody formation is not fully understood. In our study, we provide evidence for the functional role of the liver and the stimulation of plasma cell proliferation in hyperimmunoglobulinemia. We collected sera from patients with chronic liver diseases, and the level of serum immunoglobulins in patients was examined; this was also investigated in animal models of liver cirrhosis and hepatocellular carcinoma. An end-to-side microsurgical portacaval shunt was used to mimic liver dysfunction in rats. We used portal vein serum and inferior vena cava serum to immunize healthy rats and mice in order to confirm the function of the healthy liver in disposing of antigens and endotoxins from the gut. For the analysis of the state of plasma cell activation, plasma cells from mice were stained with PE-conjugated anti-CD138 and FITC-conjugated anti-BrdU for flow cytometry analysis. Hyperimmunoglobulinemia was observed both in patients with chronic liver diseases and in related animal models, and high plasma LPS levels were also observed. There was a significant increase in the activation and proliferation of plasma cell in mice immunized with antigens or LPS-positive serum compared with controls that were immunized with antigens and LPS-negative serum. We confirmed that the healthy liver plays an important role in disposing of antigens and endotoxins derived from the gut. Hyperimmunoglobulinemia in chronic liver diseases mainly arises due to the collateral circulation secondary to portal hypertension, gut antigens and endotoxins that bypass the liver and reach the antibody-producing cells.

The emergency departments (EDs) of Chinese hospitals are gradually being equipped with blood gas machines. These machines, along with the measurement of biochemical markers by the hospital laboratory, facilitate the care of patients with severe conditions who present to the ED. However, discrepancies have been noted between the Arterial Blood Gas (ABG) analyzers in the ED and the hospital laboratory autoanalyzer in relation to electrolyte and hemoglobin measurements. The present study was performed to determine whether the ABG and laboratory measurements of potassium, sodium, and hemoglobin levels are equivalent, and whether ABG analyzer results can be used to guide clinical care before the laboratory results become available.Study power analyses revealed that 200 consecutive patients who presented to our ED would allow this prospective single-center cohort study to detect significant differences between ABG- and laboratory-measured potassium, sodium, and hemoglobin levels. Paired arterial and venous blood samples were collected within 30 minutes. Arterial blood samples were measured in the ED by an ABL 90 FLEX blood gas analyzer. The biochemistry and blood cell counts of the venous samples were measured in the hospital laboratory. The potassium, sodium, and hemoglobin concentrations obtained by both methods were compared by using paired Student's t-test, Spearman's correlation, Bland-Altman plots, and Deming regression.The mean ABG and laboratory potassium values were 3.77±0.44 and 4.2±0.55, respectively (P

Treatment with short hairpin RNA (shRNA) interference therapy targeting phosphodiesterase 5a after myocardial infarction (MI) has been shown to mitigate post-MI heart failure. We investigated the mechanisms that underpin the beneficial effects of PDE5a inhibition through shRNA on post-MI heart failure.An adenoviral vector with an shRNA sequence inserted was adopted for the inhibition of phosphodiesterase 5a (Ad-shPDE5a) in vivo and in vitro. Myocardial infarction (MI) was induced in male C57BL/6J mice by left coronary artery ligation, and immediately after that, the Ad-shPDE5a was injected intramyocardially around the MI region and border areas.Four weeks post-MI, the Ad-shPDE5a-treated mice showed significant mitigation of the left ventricular (LV) dilatation and dysfunction compared to control mice. Infarction size and fibrosis were also significantly reduced in Ad-shPDE5a-treated mice. Additionally, Ad-shPDE5a treatment decreased the MI-induced inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and transforming growth factor-β1, which was confirmed in vitro in Ad-shPDE5a transfected myofibroblasts cultured under oxygen glucose deprivation. Finally, Ad-shPDE5a treatment was found to activate the myocardial Akt signaling pathway in both in vivo and in vitro experiments.These findings indicate that PDE5a inhibition by Ad-shPDE5a via the Akt signal pathway could be of significant value in the design of future therapeutics for post-MI heart failure.

This study was to evaluate the usefulness of serum thymoglobulin (Tg) in adults to assess iodine status through a 5-year cohort study which was conducted in three regions with different levels of iodine intake: mild deficiency, more than adequate, and excess, from 1999 to 2004 in China. A total of 3099 subjects over 14 years old with normal serum levels of Tg in 1999 were eligible, of whom 2448 were followed in 2004. Serum levels of thyroid hormones and thyroid autoantibodies as well as urine iodine were measured, and B-mode ultrasonography of the thyroid was performed. A general linear model was performed to determine the determinant factors of serum Tg. Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the baseline levels of serum Tg were substantially different (7.5μg/L, 5.9μg/L, and 6.8μg/L respectively, P

Little is known about the relationship between lower extremity peripheral arterial disease (PAD) and proliferative diabetic retinopathy (PDR) in type 2 diabetes (T2D). Here, we explored the relationship between sight-threatening PDR and PAD. We screened for diabetic retinopathy (DR) and PAD in hospitalized patients with T2D. Patients with a diabetic duration of more than 10 years, HbA1c ≥7.5%, eGFR ≥60 mL/min/1.73 m2 and with PDR or with no diabetic retinopathy (NDR) were eligible for this cross-sectional study. Severities of DR were graded by digital retinal photographs according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. We assessed PAD by measuring Ankle Brachial Index (ABI), Toe Brachial Index (TBI) and Doppler ultrasound. Statistical analyses were performed using SPSS 17.0 software. Of the 1544 patients, 169 patients with extreme eye (57 PDR and 112 NDR) phenotypes met the inclusion criteria. Patients with PDR had a significantly higher proportion of low ABI (≤0.99) and high ABI (≥1.3) than patients with NDR (28.1% and 15.8% vs. 14.3% and 6.2% respectively, P

TECTA-related deafness can be inherited as autosomal-dominant nonsyndromic deafness (designated DFNA) or as the autosomal-recessive version. The α-tectorin protein, which is encoded by the TECTA gene, is one of the major components of the tectorial membrane in the inner ear. Using targeted DNA capture and massively parallel sequencing (MPS), we screened 42 genes known to be responsible for human deafness in a Chinese family (Family 3187) in which common deafness mutations had been ruled out as the cause, and identified a novel mutation, c.257-262CCTTTC>GCT (p. Ser86Cys; p. Pro88del) in exon 3 of the TECTA gene in the proband and his extended family. All affected individuals in this family had moderate down-sloping hearing loss across all frequencies. To our knowledge, this is the second TECTA mutation identified in Chinese population. This study demonstrates that targeted genomic capture, MPS, and barcode technology might broaden the availability of genetic testing for individuals with undiagnosed DFNA.

OBJECTIVES: To determine whether within-visit blood pressure (BP) variability based on three measurements over minutes is associated with increased carotid intima-media thickness (IMT) and plaque in a general population. METHODS: A cross-sectional survey was performed in 2007, and a total of 1222 Beijing community residents aged 50-79 years belonging to part of the Chinese Multi-Provincial Cohort Study (CMCS) were recruited in this study. BP was measured three times at 5-minute intervals during a single visit, and the maximum absolute difference (MAD) between any two readings of three measurements was used to indicate within-visit BP variability. Carotid IMT and plaque scanned by B-mode ultrasound were identified as the surrogate end points in the intermediate stage of atherosclerosis. RESULTS: After adjustment for established cardiovascular risk factors, the odds ratio (OR) (95% confidence interval (CI)) for increased carotid IMT and internal carotid plaque associated with the highest within-visit diastolic BP (DBP) variability (MAD > mean + standard deviation (SD)) compared with participants in the lowest within-visit DBP variability (MAD ≤ mean -SD) was 4.92 (1.48-16.42) and 6.07 (1.31-28.10), respectively, in the normotensives (P = 0.01; P = 0.02). The OR (95% CI) for internal carotid plaque associated with the highest within-visit systolic BP (SBP) variability (MAD >mean +SD) compared with participants in the lowest within-visit SBP variability (MAD ≤ mean -SD) was 3.54 (1.26-10.00) in the hypertensives on antihypertensive therapy (P = 0.02). CONCLUSIONS: Within-visit DBP variability was associated with increased carotid IMT and internal carotid plaque in the normotensive population, and within-visit SBP variability was associated with internal carotid plaque in hypertensive patients undergoing antihypertensive therapy.

BackgroundThere have been few published studies on spirometric reference values for healthy children in China. We hypothesize that there would have been changes in lung function that would not have been precisely predicted by the existing spirometric reference equations. The objective of the study was to develop more accurate predictive equations for spirometric reference values for children aged 9 to 15 years in Northeast China.Methodology/principal findingsSpirometric measurements were obtained from 3,922 children, including 1,974 boys and 1,948 girls, who were randomly selected from five cities of Liaoning province, Northeast China, using the ATS (American Thoracic Society) and ERS (European Respiratory Society) standards. The data was then randomly split into a training subset containing 2078 cases and a validation subset containing 1844 cases. Predictive equations used multiple linear regression techniques with three predictor variables: height, age and weight. Model goodness of fit was examined using the coefficient of determination or the R(2) and adjusted R(2). The predicted values were compared with those obtained from the existing spirometric reference equations. The results showed the prediction equations using linear regression analysis performed well for most spirometric parameters. Paired t-tests were used to compare the predicted values obtained from the developed and existing spirometric reference equations based on the validation subset. The t-test for males was not statistically significant (p>0.01). The predictive accuracy of the developed equations was higher than the existing equations and the predictive ability of the model was also validated.Conclusion/significanceWe developed prediction equations using linear regression analysis of spirometric parameters for children aged 9-15 years in Northeast China. These equations represent the first attempt at predicting lung function for Chinese children following the ATS/ERS Task Force 2005 guidelines on spirometry standardization.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are common causes of respiratory infections in children. Diseases caused by hMPV are generally considered to be less severe than those caused by RSV; the underlying mechanisms, however, remain unknown. In the present study, the expressions of TLRs in airway epithelial cells and lungs of BALB/c mice infected by hMPV or RSV were measured in an attempt to explore the differences in the airway inflammation caused by the two viruses. Our results demonstrate that both hMPV and RSV infection upregulated the expressions of TLRs and inflammatory cytokines. Specifically, the TLR3 expression was revealed to be elevated in vitro and in mouse lungs. IFN-α produced by A549 cells after RSV or hMPV infection remained undistinguishable, whereas production of TNF-α was significantly higher after RSV infection than hMPV infection either in the presence or absence of Poly I:C. This study provides a clue that more severe clinical syndrome of RSV infection may be due to the greater magnitude of induction of airway inflammation by RSV involving TLR3 activation and production of TNF-α.

BACKGROUND: Inflammatory cytokines are involved in intervertebral disc (IVD) degeneration. Endothelin-1 (ET-1), a 21-amino-acid cytokine implicated with cartilage degradation, is secreted by vascular endothelial cells and also by many other cell types. The expression of ET-1 in human IVD cartilage endplate (CEP) and its role in disc degeneration have not been explored. METHODS AND FINDINGS: The expression of ET-1 in degenerated CEP was analyzed by immunohistochemical staining and Western blotting; ET-1 was demonstrated in cartilaginous endplate cells (CECs) by immunofluorescent staining. The ET-1 mRNA expression and protein production by CECs stimulated by tumor necrosis factor alpha (TNF-α), a pro-inflammatory cytokine, were determined by real-time PCR analysis and Western blotting, respectively. The matrix metalloprotease-1 (MMP-1), MMP-13 and tissue inhibitor of metalloproteases-1 (TIMP-1) levels in the supernatant of cultured CECs treated with ET-1 were determined using enzyme-linked immunosorbent assays. Nitric oxide (NO) release and nitric oxide synthase (NOS) activity were measured using a spectrophotometric assay. The apoptosis of CECs by ET-1 was measured by an Annexin V-FITC detection assay. The production of ET-1 in degenerated cartilage endplate was significantly higher than normal CEP. The results showed that ET-1 was expressed by CECs and modulated by TNF-α in a dose-dependent manner. ET-1 increased production of MMP-1 and MMP-13, decreased TIMP-1 production, and induced NO and NOS release by cultured CECs. The direct stimulation of CECs by ET-1 did not promote cell apoptosis. CONCLUSION: The study results suggest that ET-1 played a pivotal role in human CEP degeneration, and may be a new target for development of therapies for this condition.

MicroRNA155 plays an important role in many solid malignancies. Expression and function of miR-155 in laryngeal carcinoma have not been fully understood. This study aims to investigate the expression and function of miR-155 in laryngeal squamous cell carcinoma (LSCC), the relationship between miR-155 and its downstream target suppressor of cytokine signaling 1 (SOCS1)-STAT3 pathway, and the related clinicopathological factors. Sixty-three samples of laryngeal squamous cell carcinoma and twenty-one samples of control mucosa obtained from total laryngectomy cases were analyzed using Western blot analysis and real-time PCR. Hep-2 cells were cultured and transfected with miR-155 mimic and ASO. Cell proliferation, migration and invasion assays were used to determine the role of miR-155 in regulation of LSCC growth, migration, and invasion, respectively. The expression levels of miR-155 in LSCC were significantly higher than those in the control mucosa tissues. Downregulation of SOCS1 expression and elevated expression of STAT3 were also observed in LSCC. The relevance of the three factors were statistically significant. Moreover, knockdown of miR-155 elevated SOCS1expression level, suppressed STAT3 expression, and inhibited hep-2 cells growth, migration and invasion. Whereas overexpression of miR-155 inhibited SOCS1expression, elevated STAT3 expression, and promoted hep-2 cells growth, migration and invasion. Furthermore, the miR-155 levels in T(3) T(4) stages, and poor/moderate cell differentiation were significantly higher than those in T(2) stage and higher degree of cell differentiation. The STAT3 protein in poor/moderate cell differentiation was significantly higher than those in higher degree of cell differentiation. We firstly demonstrated the aberrant expression and function of miR-155 and itsdownstream targets in LSCC. The current findings suggest that miR-155 play promotingrole during the development of LSCC, and miR-155 may be a useful marker for the prognosis and assessment of therapeutic effects.

Glycosylation is one of the most abundant protein posttranslational modifications. Protein glycosylation plays important roles not only in eukaryotes but also in prokaryotes. To further understand the roles of protein glycosylation in prokaryotes, we developed a lectin binding assay to screen glycoproteins on an Escherichia coli proteome microarray containing 4,256 affinity-purified E.coli proteins. Twenty-three E.coli proteins that bound Wheat-Germ Agglutinin (WGA) were identified. PANTHER protein classification analysis showed that these glycoprotein candidates were highly enriched in metabolic process and catalytic activity classes. One sub-network centered on deoxyribonuclease I (sbcB) was identified. Bioinformatics analysis suggests that prokaryotic protein glycosylation may play roles in nucleotide and nucleic acid metabolism. Fifteen of the 23 glycoprotein candidates were validated by lectin (WGA) staining, thereby increasing the number of validated E. coli glycoproteins from 3 to 18. By cataloguing glycoproteins in E.coli, our study greatly extends our understanding of protein glycosylation in prokaryotes.

BackgroundMales and females exhibit different health responses to air pollution, but little is known about how exposure to air pollution affects juvenile respiratory health after analysis stratified by allergic predisposition. The aim of the present study was to assess the relationship between air pollutants and asthmatic symptoms in Chinese children selected from multiple sites in a heavily industrialized province of China, and investigate whether allergic predisposition modifies this relationship.Methodology/principal findings30139 Chinese children aged 3-to-12 years were selected from 25 districts of seven cities in northeast China in 2009. Information on respiratory health was obtained using a standard questionnaire from the American Thoracic Society. Routine air-pollution monitoring data was used for particles with an aerodynamic diameter ≤10 µm (PM(10)), sulfur dioxide (SO(2)), nitrogen dioxides (NO(2)), ozone (O(3)) and carbon monoxide (CO). A two-stage regression approach was applied in data analyses. The effect estimates were presented as odds ratios (ORs) per interquartile changes for PM(10), SO(2), NO(2), O(3), and CO. The results showed that children with allergic predisposition were more susceptible to air pollutants than children without allergic predisposition. Amongst children without an allergic predisposition, air pollution effects on asthma were stronger in males compared to females; Current asthma prevalence was related to PM(10) (ORs = 1.36 per 31 µg/m(3); 95% CI, 1.08-1.72), SO(2) (ORs = 1.38 per 21 µg/m(3); 95%CI, 1.12-1.69) only among males. However, among children with allergic predisposition, more positively associations between air pollutants and respiratory symptoms and diseases were detected in females; An increased prevalence of doctor-diagnosed asthma was significantly associated with SO(2) (ORs = 1.48 per 21 µg/m(3); 95%CI, 1.21-1.80), NO(2) (ORs = 1.26 per 10 µg/m(3); 95%CI, 1.01-1.56), and current asthma with O(3) (ORs = 1.55 per 23 µg/m(3); 95%CI, 1.18-2.04) only among females.Conclusion/significanceAmbient air pollutions were more evident in males without an allergic predisposition and more associations were detected in females with allergic predisposition.

BACKGROUND: In mammals, hair cells do not undergo spontaneous regeneration when they are damaged and result in permanent hearing loss. Previous studies in cultured Organ of Corti dissected from neonatal animals have shown that both DAPT (r-secretase inhibitor in the Notch signal pathway) treatment and Atoh1 overexpression can induce supernumerary hair cells. The effects of simultaneous DAPT treatment and Atoh1 over expression in the cells of cultured Organ of Corti from neonatal rats are still obscure. PRINCIPAL FINDINGS: In this study, we set out to investigate the interaction of DAPT treatment and Atoh1 overexpression as well as culture time and the location of basilar fragment isolated form neonatal rat inner ear. Our results showed that DAPT treatment induced more hair cells in the apical turn, while Atoh1 overexpression induced more extra hair cells in the middle turn of the cultured Organ of Corti. When used together, their effects are additive but not synergistic. In addition, the induction of supernumerary hair cells by both DAPT and Atoh1 overexpression is dependent on the treatment time and the location of the cochlear tissue. Moreover, DAPT treatment causes dramatic changes in the orientation of the stereociliary bundles of hair cells, whereas Atoh1 overexpression didn't induce drastic change of the polarity of stereociliary bundles. CONCLUSIONS/SIGNIFICANCE: Taken together, these results suggest that DAPT treatment are much more potent in inducing supernumerary hair cells than Atoh1 overexpression and that the new hair cells mainly come from the trans-differentiation of supporting cells around hair cells. The orientation change of stereociliary bundle of hair cells may be attributed to the insertion of the newly formed hair cells. The immature hair bundles on the newly formed hair cells may also contribute to the overall chaos of the stereociliary bundle of the sensory epithelia.

To estimate individual and household economic impact of cardiovascular disease (CVD) in selected low- and middle-income countries (LMIC).Empirical evidence on the microeconomic consequences of CVD in LMIC is scarce.We surveyed 1,657 recently hospitalized CVD patients (66% male; mean age 55.8 years) from Argentina, China, India, and Tanzania to evaluate the microeconomic and functional/productivity impact of CVD hospitalization. Respondents were stratified into three income groups. Median out-of-pocket expenditures for CVD treatment over 15 month follow-up ranged from 354 international dollars (2007 INT$, Tanzania, low-income) to INT$2,917 (India, high-income). Catastrophic health spending (CHS) was present in >50% of respondents in China, India, and Tanzania. Distress financing (DF) and lost income were more common in low-income respondents. After adjustment, lack of health insurance was associated with CHS in Argentina (OR 4.73 [2.56, 8.76], India (OR 3.93 [2.23, 6.90], and Tanzania (OR 3.68 [1.86, 7.26] with a marginal association in China (OR 2.05 [0.82, 5.11]). These economic effects were accompanied by substantial decreases in individual functional health and productivity.Individuals in selected LMIC bear significant financial burdens following CVD hospitalization, yet with substantial variation across and within countries. Lack of insurance may drive much of the financial stress of CVD in LMIC patients and their families.