Relationship between atmospheric pollutants and risk of death caused by cardiovascular and respiratory diseases and malignant tumors in Shenyang, China, from 2013 to 2016: an ecological research Background: Air pollutants and their pathogenic effects differ among regions and seasons. We aimed to explore the relationship between fine particulate matter (PM2.5), sulfur dioxide (SO2), and ozone-8 hours (O3-8h) concentrations in heating and non-heating seasons and the associated death risk due to cardiovascular diseases (CDs), respiratory diseases (RDs), and malignant tumors. Methods: Data were collected in Shenyang, China, from April 2013 to March 2016. We analyzed the correlation or lagged effect of atmospheric pollutant concentration, meteorological conditions, and death risk due to disorders of the circulatory system, respiratory system, and malignant tumor in heating and non-heating seasons. We also used multivariate models to analyze the association of air pollutants during holidays with the death risk due to the evaluated diseases while considering the presence or absence of meteorological factors. Results: An increase in the daily average SO2 concentration by 10 μg/m3 increased the death risk by CDs, which reached a maximum of 2.0% (95% confidence interval [CI]: 1.3%–2.7%) on lagging day 4 during the non-heating season and 0.2% (95% CI: 0.1%–0.4%) on lagging day 3 during the heating season. The risk of death caused by RDs peaked on lagging day 1 by 0.8% (95% CI: 0.4%–1.2%) during the heating season. An increase in O3-8h concentration by 10 μg/m3 increased the risk of RD-related death on lagging day 2 by 1.0% (95% CI: 0.4%–1.7%) during the non-heating season, which was significantly higher than the 0.1% (95% CI: 0–0.9%) increase during the heating season. Further, an increase in the daily average PM2.5 concentration by 10 μg/m3 increased the risk of death caused by RDs by 0.3% and 0.8% during heating and non-heating seasons, respectively, which peaked on lagging day 0. However, air pollution was not significantly associated with the risk of death caused by malignant tumors. Conclusion: Short-term exposure to PM2.5, SO2, and O3 during the non-heating season resulted in higher risks of CD-related death, followed by RD-related death.

Growth differentiation factor-15 combined with N-terminal prohormone of brain natriuretic peptide increase 1-year prognosis prediction value for patients with acute heart failure: a prospective cohort study Background: Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers. The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15 (GDF-15) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in assessing hospitalized patients with acute heart failure (AHF). Methods: In total, 260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016. Medical history and blood samples were collected within 24 h after the admission. The primary endpoint was the all-cause mortality within 1 year. The patients were divided into survival group and death group based on the endpoint. With established mortality risk factors and serum GDF-15 level, receiver-operator characteristic (ROC) analyses were performed. Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15. Results: Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors (P < 0.001). In ROC analyses, area under curve (AUC) for GDF-15 to predict 1-year mortality was 0.707 (95% confidence interval [CI]: 0.648–0.762, P < 0.001), and for NT-proBNP was 0.682 (95% CI: 0.622–0.738, P < 0.001). No statistically significant difference was found between the two markers (P = 0.650). Based on the optimal cut-offs (GDF-15: 4526.0 ng/L; NT-proBNP: 1978.0 ng/L), the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction (AUC = 0.743, 95% CI: 0.685–0.795, P < 0.001). Conclusions: GDF-15, as a prognostic marker in patients with AHF, is not inferior to NT-proBNP. Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis. Clinical trial registration: ChiCTR-ONC-12001944, http://www.chictr.org.cn.

Angiographic characteristics and in-hospital mortality among patients with ST-segment elevation myocardial infarction presenting without typical chest pain: an analysis of China Acute Myocardial Infarction registry Background: Patients with ST-segment elevation myocardial infarction (STEMI) who present without typical chest pain are associated with a poor outcome. However, whether angiographic characteristics are related to a higher risk of mortality in this population is unclear. This study aimed to investigate whether the higher mortality risk in patients with STEMI without chest pain could be explained by their “high-risk” angiographic characteristics. Methods: We used data of 12,145 patients with STEMI who was registered in China Acute Myocardial Infarction registry from January 2013 to September 2014. We compared the infarct-related artery (IRA), thrombolysis in myocardial infarction (TIMI) flow grade in the IRA, and other angiographic characteristics between patients without and those with chest pain. Multivariable logistic regression model was used to identify independent risk factor of in-hospital mortality. Results: The 2922 (24.1%) patients with STEMI presented without typical chest pain. These patients had a higher TIMI flow grade (mean TIMI flow grade: 1.00 vs. 0.94, P = 0.02) and a lower rate of IRA disease of the left anterior descending artery (44.6% vs. 51.2%, χ2 = 35.63, P < 0.01) than did those with typical chest pain. Patients without chest pain were older, more likely to have diabetes, longer time to hospital and higher Killip classification, and less likely to receive optimal medication treatment and primary percutaneous coronary intervention and higher In-hospital mortality (3.3% vs. 2.2%, χ2 = 10.57, P  < 0.01). After adjusting for multi-variables, presentation without chest pain was still an independent predictor of in-hospital death among patients with STEMI (adjusted odds ratio: 1.36, 95% confidence interval: 1.02–1.83). Conclusions: Presentation without chest pain is common and associated with a higher in-hospital mortality risk in patients with acute myocardial infarction. Our results indicate that their poor prognosis is associated with baseline patient characteristics and delayed treatment, but not angiographic lesion characteristics. Clinical trial registration: NCT01874691, https://clinicaltrials.gov.

Optimal strategy of switching from clopidogrel to ticagrelor in Chinese acute coronary syndrome patients with complicated coronary artery disease: the switching from clopidogrel to ticagrelor (SHIFT-CACS) study Background: The dose and time point for switching from clopidogrel to ticagrelor remain controversial, especially for Chinese acute coronary syndrome (ACS) patients with complicated coronary artery disease (CAD). Hence, the purpose of this study was to further explore the optimal dose and time point for the switching strategy to balance the increase in platelet inhibition and the decrease in adverse events in Chinese ACS patients with complicated CAD managed by percutaneous coronary intervention (PCI). Methods: From July 2017 to December 2017, the prospective, randomized, open-label study (the SwitcHIng from clopidogrel to ticagrelor study) assigned the eligible Chinese ACS patients with complicated CAD managed by PCI (n = 102) for 90 mg of ticagrelor at 12 h (T-90 mg-12 h), 90 mg of ticagrelor at 24 h (T-90 mg-24h) or 180 mg ticagrelor at 24 h (T-180 mg-24 h) after the last dose of clopidogrel. The primary endpoint was the comparison of maximal platelet aggregation (MPA) values at 2 h after switching strategies among the three groups. In addition, the MPA values at baseline, 8 h and before discharge and the rates of high on-treatment platelet reactivity were evaluated, the incidences of bleeding episodes and dyspnea during hospitalization and at 30-day follow-up in our study were also recorded. The MPA was measured by light transmittance aggregometry in our study. A repeated-measures analysis of variance (ANOVA) model and one-way ANOVA were used to compare data for the primary endpoint. Results: The MPA values were significantly decreased in the T-180 mg-24 h group compared with the T-90 mg-12 h group (P = 0.017) and decreased numerically compared with the T-90 mg-24 h group (P = 0.072) at 2 h. In particular, the MPA values were markedly reduced in the T-90 mg-24 h group compared with the T-90 mg-12 h group at 8 h after switching treatment (P = 0.002). There was no significant difference among the three groups in all bleedings and dyspnea events. Conclusions: The optimal treatment strategy recommended in this study for Chinese ACS patients with complicated CAD managed by PCI is 180 or 90 mg of ticagrelor at 24 h after the last dose of clopidogrel. In addition, a negative interaction was detected in this study between the overlap for clopidogrel and ticagrelor at 12 h after the last dose of clopidogrel. Trial Registration: ClinicalTrials.gov, NCT03577652; http://clinicaltrials.gov/ct2/show/NCT03577652.

Neurophysiological predictors of aphasia recovery in patients with large left-hemispheric infarction: a mismatch negativity study Background: Although the rehabilitation of aphasia has been extensively studied, the prediction of language outcome still has not received sufficient attention. The aim of this study was to predict the language outcome using mismatch negativity (MMN) in patients with large left-hemispheric infarction. Methods: MMN was elicited by an oddball paradigm in which a standard tone (1000 Hz) and deviant tone (1500 Hz) were presented at 90% and 10% of the number of tones, respectively. The mean amplitudes and laterality indexes (LIs) of MMN were measured over the prefrontal, frontal, central, parietal, temporal, and perisylvian electrodes and both hemispheres during the first 7 days (session 1) and 10 to 20 days (session 2) post-onset. Mixed three-way analysis of variance (ANOVA) was used to investigate differences in these factors between two aphasia groups (the good recovery group and poor recovery group). The predictive value of the most significant LI was also compared with the score of National Institutes of Health Stroke Scale score and low-density volume on computed tomography. Results: A total of 18 patients were enrolled in this study. Mixed three-way ANOVA showed no interaction effect of session × region of interest (ROI) × group (F [3.59, 57.38] = 1.301, P = 0.282) and no interaction effect of ROI × group (F [1.81, 29.01] = 0.71, P = 0.487) and session × group (F [1.00, 16.00] = 0.084, P = 0.776) for MMN amplitude. No interaction effect of session × ROI × group (F [1.79, 28.58] = 0.62, P = 0.530), but an interaction effect of session × group (F [1.00, 16.00] = 5.21, P = 0.036) was found for LIs. In the poor recovery group, the LIs of MMN over all the ROIs, except the parietal area, became more negative at session 2 than those at session 1 (P < 0.05), but this effect was not observed in the good recovery group. Additionally, significant differences were observed in the LIs at session 2 between the two groups (P < 0.05). The LI over the perisylvian area at session 2 had the highest predictive value with an area under the curve of 0.963 (95% confidence interval: 0.884–1.000). An LI score >−0.36 over the perisylvian area suggested good recovery, but a score <−0.36 suggested poor recovery. The LI cut-off value of −0.36 had the highest sensitivity (90.0%) and specificity (87.5%) for predicting a good language outcome at 3 months post-stroke. Conclusion: LIs of MMN amplitudes at approximately 2 weeks post left-hemisphere stroke serve as more sensitive predictors of language outcome, among which the LI over the perisylvian area exhibits the best predictive value.

Selective impairment of musical emotion recognition in patients with amnesic mild cognitive impairment and mild to moderate Alzheimer disease Background Patients with Alzheimer disease (AD) and amnesic mild cognitive impairment (aMCI) have deficits in emotion recognition. However, it has not yet been determined whether patients with AD and aMCI also experience difficulty in recognizing the emotions conveyed by music. This study was conducted to investigate whether musical emotion recognition is impaired or retained in patients with AD and aMCI. Methods All patients were recruited from the First Affiliated Hospital of Anhui Medical University between March 1, 2015 and January 31, 2017. Using the musical emotion recognition test, patients with AD (n = 16), patients with aMCI (n = 19), and healthy controls (HCs, n = 16) were required to choose one of four emotional labels (happy, sad, peaceful, and fearful) that matched each musical excerpt. Emotion recognition scores in three groups were compared using one-way analysis of variance (ANOVA) test. We also investigated the relationship between the emotion recognition scores and Mini-Mental State Examination (MMSE) using Pearson's correlation analysis test in patients with AD and aMCI. Results Compared to the HC group, both of the patient groups showed deficits in the recognition of fearful musical emotions (HC: 7.88 ± 1.36; aMCI: 5.05 ± 2.34; AD: 3.69 ± 2.02), with results of a one-way ANOVA confirming a significant main effect of group (F(2,50) = 18.70, P < 0.001). No significant differences were present among the three groups for the happy (F(2,50)=2.57, P = 0.09), peaceful (F(2,50) = 0.38, P = 0.09), or sad (F(2,50) = 2.50, P = 0.09) musical emotions. The recognition of fearful musical emotion was positively associated with general cognition, which was evaluated by MMSE in patients with AD and aMCI (r = 0.578, P < 0.001). The correlations between the MMSE scores and recognition of the remaining emotions were not significant (happy, r = 0.228, P = 0.11; peaceful, r = 0.047, P = 0.74; sad, r = 0.207, P = 0.15). Conclusion This study showed that both patients with AD and aMCI had decreased ability to distinguish fearful emotions, which might be correlated with diminished cognitive function.

First line nucleos(t)ide analog monotherapy is more cost-effective than combination strategies in hepatitis B e antigen-positive chronic hepatitis B patients in China Background: Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed “functional cure,” based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective. Methods: A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively. Results: In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA − PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results. Conclusion: Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

Association between cardiopulmonary bypass time and 90-day post-operative mortality in patients undergoing arch replacement with the frozen elephant trunk: a retrospective cohort study Background The aortic arch replacement and cardiopulmonary bypass (CPB) are both associated with the early mortality after cardiothoracic surgery. This study aimed to investigate the relationship between CPB time and 90-day post-operative mortality in patients undergoing aortic arch surgery using the frozen elephant trunk (FET) technique with selective ante-grade cerebral perfusion (SACP). Methods We retrospectively reviewed data of 377 adult patients undergoing aortic arch surgery via FET with SACP from July 1, 2017 to December 31, 2018 at Beijing Anzhen Hospital. The baseline characteristics, intra-operative data, and post-operative data were collected. Univariate and multivariate Cox regression analyses were used to determine independent predictors of 90-day post-operative mortality. Results The 90-day post-operative mortality was 13.53%. The 78.51% of patients were men. There were 318 (84.35%) type A aortic dissections and 28 (7.43%) aortic aneurysms. Among those, 264 (70.03%) were emergency operations. Median CPB time was 202.0 (176.0, 227.0) min. Multivariate Cox regression analysis revealed that CPB time was independently associated with 90-day post-operative mortality after adjusting confounding factors (hazard ratio: 1.21/10 min increase in CPB time, 95% confidence interval: 1.15–1.27, P < 0.001). Kaplan-Meier analysis based on CPB time tertiles revealed that the top tertile (median 236.0 min) was associated with reduced survival rate compared with middle and bottom tertiles (P < 0.001). Each sub-group analysis based on the complexity of the underlying disease process showed similar associations between CPB time and 90-day post-operative mortality. Conclusions CPB time remains a significant factor in determining 90-day post-operative mortality in patients undergoing aortic arch surgery using FET with SACP. Surgeons should be aware of the relationship between CPB time and 90-day post-operative mortality during operative procedures and avoid extended CPB time as far as possible.

Optimal waiting period for fresh embryo transfer after hysteroscopic adhesiolysis: a retrospective cohort study Background: Very few studies have been conducted regarding the optimal time interval between hysteroscopic adhesiolysis and the embryo transfer (ET). Investigation of this optimal time may be helpful for assisted reproductive technology. Therefore, we investigated effects of the interval between hysteroscopic adhesiolysis and ET upon in vitro fertilization (IVF) cycle outcomes. Methods: Patients were recruited between January 2014 and September 2017 at the Reproductive Hospital Affiliated to Shandong University. Patients who were diagnosed with intra-uterine adhesion (IUA) and underwent hysteroscopic adhesiolysis before fresh IVF-ET or intra-cytoplasmic sperm injection cycles were classified into three groups according to the interval between hysteroscopic adhesiolysis and ET: less than 90 days (Group 1), 90 to 180 days (Group 2), and greater than 180 days (Group 3). Baseline characteristics, controlled ovarian stimulation (COS) response, and pregnancy outcomes after ET were compared. Analysis of variance or non-parametric tests were used to test numerical data. The Pearson's Chi-squared test was used to test categorical data. Results: A total of 312 patients were recruited as follows: 112 in Group 1, 137 in Group 2, and 63 in Group 3. There were no differences in baseline and COS characteristics among the three groups. The live-birth rate in Group 2 (40.1%) was significantly higher than that in Group 1 (17.9%; χ2 = 14.545, P < 0.001). There were no significant differences in the rates of biochemical, ongoing, and clinical pregnancy, and biochemical and clinical pregnancy abortion, as well as stillbirth among the groups. In the mild IUA patients, the live-birth rate was significantly higher in Group 2 (42.6%) compared with Group 1 (22%; χ2 = 8.413, P = 0.004). In the moderate IUA patients, Group 2 (35.7%) had a higher frequency of live births than Group 1 (6.7%; χ2 = 8.187, P = 0.004). Conclusions: The optimal waiting period for fresh ET after hysteroscopic adhesiolysis was 90 to 180 days in the current study.

Involvement of phosphatase and tensin homolog-induced putative kinase 1–Parkin-mediated mitophagy in septic acute kidney injury Background: Studies have reported mitophagy activation in renal tubular epithelial cells (RTECs) in acute kidney injury (AKI). Phosphatase and tensin homolog-induced putative kinase 1 (PINK1) and E3 ubiquitin-protein ligase Parkin are involved in mitophagy regulation; however, little is known about the role of PINK1-Parkin mitophagy in septic AKI. Here we investigated whether the PINK1-Parkin mitophagy pathway is involved in septic AKI and its effects on cell apoptosis in vitro and on renal functions in vivo. Methods: Mitophagy-related gene expression was determined using Western blot assay in human RTEC cell line HK-2 stimulated with bacterial lipopolysaccharide (LPS) and in RTECs from septic AKI rats induced by cecal ligation and perforation (CLP). Autophagy-related ultrastructural features in rat RTECs were observed using electron microscopy. Gain- and loss-of-function approaches were performed to investigate the role of the PINK1-Parkin pathway in HK-2 cell mitophagy. Autophagy activators and inhibitors were used to assess the effects of mitophagy modulation on cell apoptosis in vitro and on renal functions in vivo. Results: LPS stimulation could significantly induce LC3-II and BECN-1 protein expression (LC3-II: 1.72 ± 0.05 vs. 1.00 ± 0.05, P < 0.05; BECN-1: 5.33 ± 0.57 vs. 1.00 ± 0.14, P < 0.05) at 4 h in vitro. Similarly, LC3-II, and BECN-1 protein levels were significantly increased and peaked at 2 h after CLP (LC3-II: 3.33 ± 0.12 vs. 1.03 ± 0.15, P < 0.05; BECN-1: 1.57 ± 0.26 vs. 1.02 ± 0.11, P < 0.05) in vivo compared with those after sham operation. Mitochondrial deformation and mitolysosome-mediated mitochondria clearance were observed in RTECs from septic rats. PINK1 knockdown significantly attenuated LC3-II protein expression (1.35 ± 0.21 vs. 2.38 ± 0.22, P < 0.05), whereas PINK1 overexpression markedly enhanced LC3-II protein expression (2.07 ± 0.21 vs. 1.29 ± 0.19, P < 0.05) compared with LPS-stimulated HK-2 cells. LPS-induced proapoptotic protein expression remained unchanged in autophagy activator-treated HK-2 cells and was significantly attenuated in PINK1-overexpressing cells, but was remarkably upregulated in autophagy inhibitor-treated and in PINK1-depleted cells. Consistent results were observed in flow cytometric apoptosis assay and in renal function indicators in rats. Conclusion: PINK1-Parkin-mediated mitophagy might play a protective role in septic AKI, serving as a potential therapeutic target for septic AKI.