The association between the scarlet fever and meteorological factors, air pollutants and their interactions in children in northwest China.

Scarlet fever (SF) is an acute respiratory transmitted disease that primarily affects children. The influence of meteorological factors and air pollutants on SF in children has been proved, but the relevant evidence in Northwest China is still lacking. Based on the weekly reported cases of SF in children in Lanzhou, northwest China, from 2014 to 2018, we used geographical detectors, distributed lag nonlinear models (DLNM), and bivariate response models to explore the influence of meteorological factors and air pollutants with SF. It was found that ozone (O3), carbon monoxide (CO), sulfur dioxide (SO2), temperature, pressure, water vapor pressure and wind speed were significantly correlated with SF based on geographical detectors. With the median as reference, the influence of high temperature, low pressure and high pressure on SF has a risk effect (relative risk (RR) > 1), and under extreme conditions, the dangerous effect was still significant. High O3 had the strongest effect at a 6-week delay, with an RR of 5.43 (95%CI: 1.74,16.96). The risk effect of high SO2 was strongest in the week of exposure, and the maximum risk effect was 1.37 (95%CI: 1.08,1.73). The interactions showed synergistic effects between high temperatures and O3, high pressure and high SO2, high nitrogen dioxide (NO2) and high particulate matter with diameter of less than 10 µm (PM10), respectively. In conclusion, high temperature, pressure, high O3 and SO2 were the most important factors affecting the occurrence of SF in children, which will provide theoretical support for follow-up research and disease prevention policy formulation.

Macrophage ALDH2 (Aldehyde Dehydrogenase 2) Stabilizing Rac2 Is Required for Efferocytosis Internalization and Reduction of Atherosclerosis Development.

BACKGROUND: Clinical studies show that the most common single-point mutation in humans, ALDH2 (aldehyde dehydrogenase 2) rs671 mutation, is a risk factor for the development and poor prognosis of atherosclerotic cardiovascular diseases, but the underlying mechanism remains unclear. Apoptotic cells are phagocytosed and eliminated by macrophage efferocytosis during atherosclerosis, and enhancement of arterial macrophage efferocytosis reduces atherosclerosis development. METHODS: Plaque areas, necrotic core size, apoptosis, and efferocytosis in aortic lesions were investigated in APOE-/- mice with bone marrow transplanted from APOE-/-ALDH2-/- and APOE-/- mice. RNA-seq, proteomics, and immunoprecipitation experiments were used to screen and validate signaling pathways affected by ALDH2. Efferocytosis and protein levels were verified in human macrophages from wild-type and rs671 mutation populations. RESULTS: We found that transplanting bone marrow from APOE-/-ALDH2-/- to APOE-/- mice significantly increased atherosclerosis plaques compared with transplanting bone marrow from APOE-/- to APOE-/- mice. In addition to defective efferocytosis in plaques of APOE-/- mice bone marrow transplanted from APOE-/-ALDH2-/- mice in vivo, macrophages from ALDH2-/- mice also showed significantly impaired efferocytotic activity in vitro. Subsequent RNA-seq, proteomics, and immunoprecipitation experiments showed that wild-type ALDH2 directly interacted with Rac2 and attenuated its degradation due to decreasing the K48-linked polyubiquitination of lysine 123 in Rac2, whereas the rs671 mutant markedly destabilized Rac2. Furthermore, Rac2 played a more crucial role than other Rho GTPases in the internalization process in which Rac2 was up-regulated, activated, and clustered into dots. Overexpression of wild-type ALDH2 in ALDH2-/- macrophages, rather than the rs671 mutant, rescued Rac2 degradation and defective efferocytosis. More importantly, ALDH2 rs671 in human macrophages dampened the apoptotic cells induced upregulation of Rac2 and subsequent efferocytosis. CONCLUSIONS: Our study has uncovered a pivotal role of the ALDH2-Rac2 axis in mediating efferocytosis during atherosclerosis, highlighting a potential therapeutic strategy in cardiovascular diseases, especially for ALDH2 rs671 mutation carriers.

Long-distance laser Doppler water flow velocimetry method based on adaptive Gaussian weighted integration.

Velocity measurement has a high application value in hydrological monitoring and flood disaster warning. The long-distance laser Doppler water flow velocimetry technology has the advantage of strong anti-interference ability and high spatial resolution, and it can realize the high-precision measurement of water flow velocity. Because water flow has low reflectance characteristics, how to extract Doppler frequency from weak non-stationary coherent signals is a crucial problem to be solved to realize long-distance water flow velocity measurement. However, the classical method requires the time domain signal to have high stationarity and is not suitable for processing the coherent signal in the water flow velocity measurement. Aiming at this problem, we proposed a water flow velocimetry method based on adaptive Gaussian weighted integral (AGWI). First, the spectral characteristics of the coherent signal are analyzed in detail, and a statistical model of weak non-stationary signals is established. A second-order Kaiser self-multiplication window (KSMW) is designed to suppress spectral leakage for the asynchronously sampled data. Then, an adaptive homogenization power spectral subtraction (AHPSS) is designed to reduce system noise. Finally, the Doppler spectrum reconstruction and Doppler frequency estimation are performed using the AGWI method to obtain the Doppler frequency, which is further processed to get the water flow velocity. The experimental results show that the method proposed in this paper can achieve accurate and stable measurement of river surface velocity under long-distance conditions.

Long-distance laser Doppler water flow velocimetry method based on adaptive Gaussian weighted integration: publisher's note.

This publisher's note serves to correct an error in Appl. Opt.62, A1 (2023)APOPAI0003-693510.1364/AO.473632.

Influence and prediction of meteorological factors on brucellosis in a northwest region of China.

This paper aims to study the cumulative lag effect of meteorological factors on brucellosis incidence and the prediction performance based on Random Forest model. The monthly number of brucellosis cases and meteorological data from 2015 to 2019 in Yongchang of Gansu Province, northwest China, were used to build distributed lag nonlinear model (DLNM). The number of brucellosis cases of lag 1 month and meteorological data from 2015 to 2018 were used to build RF model to predict the brucellosis incidence in 2019. Meanwhile, SARIMA model was established to compare the prediction performance with RF model according to R2 and RMSE. The results indicated that the population had a high incidence risk at temperature between 5 and 13 °C and lag between 0 and 18 days, sunshine duration between 225 and 260 h and lag between 0 and 1 month, and atmosphere pressure between 789 and 793.5 hPa and lag between 0 and 18 days. The R2 and RMSE of train set and test set in RF model were 0.903, 1.609, 0.824, and 2.657, respectively, and the R2 and RMSE in SARIMA model were 0.530 and 7.008. This study found significant nonlinear and lag associations between meteorological factors and brucellosis incidence. The prediction performance of RF model was more accurate and practical compared with SARIMA model.

The role of aldehyde dehydrogenase 2 in cardiovascular disease.

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme involved in the detoxification of alcohol-derived acetaldehyde and endogenous aldehydes. The inactivating ALDH2 rs671 polymorphism, present in up to 8% of the global population and in up to 50% of the East Asian population, is associated with increased risk of cardiovascular conditions such as coronary artery disease, alcohol-induced cardiac dysfunction, pulmonary arterial hypertension, heart failure and drug-induced cardiotoxicity. Although numerous studies have attributed an accumulation of aldehydes (secondary to alcohol consumption, ischaemia or elevated oxidative stress) to an increased risk of cardiovascular disease (CVD), this accumulation alone does not explain the emerging protective role of ALDH2 rs671 against ageing-related cardiac dysfunction and the development of aortic aneurysm or dissection. ALDH2 can also modulate risk factors associated with atherosclerosis, such as cholesterol biosynthesis and HDL biogenesis in hepatocytes and foam cell formation and efferocytosis in macrophages, via non-enzymatic pathways. In this Review, we summarize the basic biology and the clinical relevance of the enzymatic and non-enzymatic, tissue-specific roles of ALDH2 in CVD, and discuss the future directions in the research and development of therapeutic strategies targeting ALDH2. A thorough understanding of the complex roles of ALDH2 in CVD will improve the diagnosis, management and prognosis of patients with CVD who harbour the ALDH2 rs671 polymorphism.

Chain-mediating effect of interaction between telomeres and mitochondria under oxidative stress in coke oven workers.

Coke oven emissions (COEs) exposure leads to oxidative stress, an imbalance between oxidant production and antioxidant defence in the body, which then leads to shortened relative telomere length (RTL) and reduced mitochondrial DNA copy number (mtDNAcn), ultimately leading to ageing and disease. By analysing the relationship among COEs, oxidative stress, RTL and mtDNAcn, we investigated the chain-mediating effects of oxidative stress and telomeres on mitochondrial damage and mitochondria on telomere damage in coke oven workers. A total of 779 subjects were included in the study. Cumulative COEs exposure concentrations were estimated, and the RTL and mtDNAcn of peripheral blood leukocytes were measured using real-time fluorescence quantitative PCR. Total antioxidant capacity (T-AOC) was measured to reflect the level of oxidative stress. The data were statistically analysed using SPSS 21.0 software and discussed using mediation effect analysis. After adjusting for age, sex, smoking, drinking and BMI, generalised linear model revealed dose-response associations between COEs and T-AOC, RTL and mtDNAcn, respectively. (Ptrend < 0.05). The results of chain-mediating effect showed that the proportion of the chain-mediating effect of "CED-COEs→T-AOC→ RTL→mtDNAcn" was 0.82% (ß = -0.0005, 95% CI = [-0.0012, -0.0001]), and the proportion of the chain-mediating effect of "CED-COEs→T-AOC→ mtDNAcn → RTL ″ was 2.64% (ß = -0.0013, 95% CI = [-0.0025, -0.0004]). After oxidative stress is induced by COEs, mitochondria and telomeres may interact with each other while leading further to potential bodily damage. This study provides clues to explore the association between mitochondria and telomeres.

Fine and coarse particulate air pollution and out-of-hospital cardiac arrest onset: a nationwide case-crossover study in China.

Out-of-hospital cardiac arrest (OHCA) is a global public health concern. Nationwide studies on the effects of short-term exposure to particulate matter (PM) on OHCA risk are rare in regions with high PM levels, and evidence for coarse PM (PM2.5-10) is limited and inconsistent. To evaluate the associations between fine PM (PM2.5) and PM2.5-10 and OHCA onset, a time-stratified case-crossover study was conducted on 77,261 patients with cardiac OHCA in 26 cities across China in 2020. Daily PM2.5 and PM2.5-10 concentrations were assessed with high-resolution and full-coverage PM estimations. Conditional logistic regression models were applied in analyses. Each interquartile range of PM increase in 3-day moving average was associated with an increased risk of cardiac OHCA onset of 2.37% (95% CI, 1.20-3.56%) for PM2.5 and 2.12% (95% CI, 0.70-3.56%) for PM2.5-10. Stratified analyses showed higher susceptibility in patients over 75 years for PM2.5 exposure and with diabetes for PM2.5-10. This first nationwide study in region with high PM levels and great PM variability found not only PM2.5 but also PM2.5-10 were associated with a higher risk of OHCA onset, which could add powerful epidemiological evidence to this field and provide new evidence for the formulation of air quality guidelines.

Association Between Air Pollutants and Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Time Stratified Case-Crossover Design With a Distributed Lag Nonlinear Model.

Acute exacerbation of chronic obstruction pulmonary disease (AECOPD) as a respiratory disease, is considered to be related to air pollution by more and more studies. However, the evidence on how air pollution affect the incidence of AECOPD and whether there are population differences is still insufficient. Therefore, we select PM10, PM2.5, SO2, NO2, CO, and O3 as representatives combined with daily AECOPD admission data from 1 January 2015 to 26 June 2016 in the rural areas of Qingyang, northwestern China to explore the associations of air pollution with AECOPD. Based on a time-stratified case-crossover design, we constructed a distributed lag nonlinear model to qualify the single and cumulative lagged effects of air pollution on AECOPD. Stratified related risks by sex and age were also reported. The cumulative exposure-response curves were approximately linear for PM2.5, "V"-shaped for PM10, "U"-shaped for NO2 and inverted-"V" for SO2, CO and O3. Exposure to high-PM2.5 (42 µg/m3), high-PM10 (91 µg/m3), high-SO2 (58 µg/m3), low-NO2 (12 µg/m3), and high-CO (1.55 mg/m3) increased the risk of AECOPD. Females aged 15-64 were more susceptible under extreme concentrations of PM2.5, SO2, CO, and low-PM10 than other subgroups. In addition, adults aged 15-64 were more sensitive to extreme concentrations of NO2 compared with the elderly ≥65 years old, while the latter were more sensitive to high-PM10. High-SO2, high-NO2, and extreme concentrations of PM2.5 had the greatest effects on the day of exposure, while low-SO2 and low-CO had lagged effects on AECOPD. Precautionary measures should be taken with a focus on vulnerable subgroups, to control hospitalization for AECOPD associated with air pollutants.

Hydrogen therapy after resuscitation improves myocardial injury involving inhibition of autophagy in an asphyxial rat model of cardiac arrest.

Hydrogen (H2) therapy is a therapeutic strategy using molecular H2. Due to its ability to regulate cell homeostasis, H2 therapy has exhibited marked therapeutic effects on a number of oxidative stress-associated diseases. The present study investigated the effectiveness of H2 therapy in protecting against myocardial injury in a rat model of asphyxial cardiac arrest and cardiopulmonary resuscitation. Rats underwent 10-min asphyxia-induced cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), and were randomly divided into control and H2 therapy groups. After resuscitation, the H2 therapy group was administered room air mixed with 2% H2 gas for respiration. During CA/CPR, the arterial pressure and heart rate were measured every minute. Survival rate, cardiac function, myocardial injury biomarkers creatine kinase-MB and cardiac troponin-T, and histopathological changes were evaluated to determine the protective effects of H2 therapy in CA/CPR. Immunohistochemistry and western blot analysis were used to determine the expression levels of autophagy-associated proteins. In vitro, H9C2 cells were subjected to hypoxia/reoxygenation and H2-rich medium was used in H2 treatment groups. Western blotting and immunofluorescence were used to observe the expression levels of autophagy-associated proteins. Moreover, an adenovirus-monomeric red fluorescent protein-green fluorescent protein-LC3 construct was used to explore the dynamics of autophagy in the H9C2 cells. The results showed that H2 therapy significantly improved post-resuscitation survival and cardiac function. H2 therapy also improved mitochondrial mass and decreased autophagosome numbers in cardiomyocytes after resuscitation. The treatment inhibited autophagy activation, with lower expression levels of autophagy-associated proteins and decreased autophagosome formation in vivo and vitro. In conclusion, H2 gas inhalation after return of spontaneous circulation improved cardiac function via the inhibition of autophagy.

Impact of the expanded program on immunization on the incidence of Japanese encephalitis in different regions of Mainland China: An interrupt time series analysis.

In 2008, Mainland China included the Japanese encephalitis (JE) vaccine in the Expanded Program on Immunization (EPI) to control the JE epidemic. However, Northwest China experienced the largest JE outbreak since 1994 in 2018, and the effects of the EPI in different regions are unclear. Therefore, we used an interrupted time series design to evaluate the effects of the EPI in different regions. In this study, ß1 and ß1+ß3 represented the slope or trend of the JE incidence before and after the EPI, respectively; ß2 was the level change of the JE incidence immediately after the EPI; ß3 represented the slope change of the JE incidence before and after the EPI. We found that the JE incidence in all regions showed a decreasing trend before the EPI (ß1<0.000, P<0.05). The JE incidence in Mainland China (ß2=-7.669, P<0.05), East China (ß2=-9.791, P<0.05), Central China (ß2=-10.695, P<0.05), South China (ß2=-6.551, P<0.05) and Southwest China (ß2=-2.216, P<0.05) decreased by 7.669/100,000, 9.791/100,000, 10.695/100,000, 6.551/100,000 and 2.216/100,000 immediately after the EPI, and the EPI had short-term effects on the JE incidence in these regions. The slope of the JE incidence in Mainland China (ß3=0.272, P<0.05), East China (ß3=0.337, P<0.05), Central China (ß3=0.381, P<0.05), South China (ß3=0.254, P<0.05) and Southwest China (ß3=0.081, P<0.05) increased by 0.272, 0.337, 0.381, 0.254 and 0.081 after the EPI, and the EPI had long-term effects on the JE incidence in these regions. The JE incidence in many regions (excluding North China) showed a decreasing trend after the EPI (ß1+ß3 <0.000). Northwest China (GDP from 2008 to 2020 ranked last in Mainland China) and Southwest China (GDP from 2008 to 2020 ranked fifth in Mainland China), with underdeveloped economy, used to be low-epidemic regions of JE, but they have become high-epidemic regions in recent years. Economic development may contribute to the geographic variations in the effects of the EPI. Therefore, it is significant for JE control in Mainland China to increase support for underdeveloped regions and adjust the vaccine strategy according to the new epidemic situation of JE.

A comparison of clinical manifestations of Japanese encephalitis between children and adults in Gansu Province, Northwest China (2005-2020).

Japanese encephalitis (JE), a mosquito-borne zoonotic disease, has emerged as a major public health concern around the world. Previous research has shown that JE has serious sequelae, and the recent shift in the population from children to adults presents a significant challenge for JE treatment and prevention. Therefore, we examined the differences in clinical manifestations (clinical symptoms, clinical signs, complications, and clinical typing) of JE between children and adults over the 15 years in Gansu Province to provide a theoretical basis for better response to JE treatment. Clinical typing was found to be statistically significant in the child versus adult groups and the groups with or without vaccination. Only the dysfunction of consciousness differed statistically between children with and without vaccination, whereas neurological symptoms such as vomiting (jet vomiting), irritability, drowsiness, convulsions, and hyperspasmia differed statistically between children and adults, and the rest of the symptoms did not differ statistically. Only pupil size changes were statistically different in clinical signs between the children with and without vaccination, while blood pressure changes, change in pupil size, positive meningeal stimulation signs, and positive pathological reflexes (increased muscle tone and Babinski's sign) were statistically different between adults and children. Bronchopneumonia was the most common complication, especially in adults. Therefore, the authors believe that children and adults differ in some clinical manifestations and propose that efforts should be directed toward developing individualized treatment plans for different age groups and employing more effective supportive treatment for various populations. In addition, we suggest expanding the coverage of the JE vaccine and increasing overall vaccination rates and adopting multiple measures in conjunction with JE prevention and control.

Effect of different vaccine strategies for the control of Japanese encephalitis in mainland China from 1961 to 2020: A quantitative analysis.

BACKGROUND: We aimed to quantify the impact of each vaccine strategy (including the P3-inactivated vaccine strategy [1968-1987], the SA 14-14-2 live-attenuated vaccine strategy [1988-2007], and the Expanded Program on Immunization [EPI, 2008-2020]) on the incidence of Japanese encephalitis (JE) in regions with different economic development levels. METHODS: The JE incidence in mainland China from 1961 to 2020 was summarized by year, then modeled and analyzed using an interrupted time series analysis. RESULTS: After the P3-inactivated vaccine was used, the JE incidence in Eastern China, Central China, Western China and Northeast China in 1968 decreased by 39.80 % (IRR = 0.602, P < 0.001), 7.80 % (IRR = 0.922, P < 0.001), 10.80 % (IRR = 0.892, P < 0.001) and 31.90 % (IRR = 0.681, P < 0.001); the slope/trend of the JE incidence from 1968 to 1987 decreased by 30.80 % (IRR = 0.692, P < 0.001), 29.30 % (IRR = 0.707, P < 0.001), 33.00 % (IRR = 0.670, P < 0.001) and 41.20 % (IRR = 0.588, P < 0.001). After the SA 14-14-2 live-attenuated vaccine was used, the JE incidence in Eastern China and Northeast China in 1988 decreased by 2.60 % (IRR = 0.974, P = 0.009) and 14.70 % (IRR = 0.853, P < 0.001); the slope/trend of the JE incidence in Eastern China and Central China from 1988 to 2007 decreased by 4.60 % (IRR = 0.954, P < 0.001) and 4.70 % (IRR = 0.953, P < 0.001). After the EPI was implemented, the JE incidence in Eastern China, Central China and Western China in 2008 decreased by 10.50 % (IRR = 0.895, P = 0.013), 18.00 % (IRR = 0.820, P < 0.001) and 24.20 % (IRR = 0.758, P < 0.001), the slope/trend of the JE incidence in Eastern China from 2008 to 2020 decreased by 17.80 % (IRR = 0.822, P < 0.001). CONCLUSIONS: Each vaccine strategy has different effects on the JE incidence in regions with different economic development. Additionally, some economically underdeveloped regions have gradually become the main areas of the JE outbreak. Therefore, mainland China should provide economic assistance to areas with low economic development and improve JE vaccination plans in the future to control the epidemic of JE.

Comparison of Safety and Efficacy Between Clopidogrel and Ticagrelor in Elderly Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Background: Dual antiplatelet therapy combining aspirin with a P2Y12 adenosine diphosphate receptor inhibitor is a therapeutic mainstay for acute coronary syndrome (ACS). However, the optimal choice of P2Y12 adenosine diphosphate receptor inhibitor in elderly (aged ≥65 years) patients remains controversial. We conducted a meta-analysis to compare the efficacy and safety of ticagrelor and clopidogrel in elderly patients with ACS. Methods: We comprehensively searched in Web of Science, EMBASE, PubMed, and Cochrane databases through 29th March, 2021 for eligible randomized controlled trials (RCTs) comparing the efficacy and safety of ticagrelor or clopidogrel plus aspirin in elderly patients with ACS. Four studies were included in the final analysis. A fixed effects model or random effects model was applied to analyze risk ratios (RRs) and hazard ratios (HRs) across studies, and I2 to assess heterogeneity. Results: A total number of 4429 elderly patients with ACS were included in this analysis, of whom 2170 (49.0%) patients received aspirin plus ticagrelor and 2259 (51.0%) received aspirin plus clopidogrel. The ticagrelor group showed a significant advantage over the clopidogrel group concerning all-cause mortality (HR 0.78, 95% CI 0.63-0.96, I2 = 0%; RR 0.79, 95% CI 0.66-0.95, I2 = 0%) and cardiovascular death (HR 0.71, 95% CI 0.56-0.91, I2 = 0%; RR 0.76, 95% CI 0.62-0.94, I2 = 5%) but owned a higher risk of PLATO major or minor bleeding (HR 1.46, 95% CI 1.13-1.89, I2 = 0%; RR 1.40, 95% CI 1.11-1.76, I2 = 0%). Both the groups showed no significant difference regarding major adverse cardiovascular events (MACEs) (HR 1.06, 95% CI 0.68-1.65, I2 = 77%; RR 1.04, 95% CI 0.69-1.58, I2 = 77%). Conclusion: For elderly ACS patients, aspirin plus ticagrelor reduces cardiovascular death and all-cause mortality but increases the risk of bleeding. Herein, aspirin plus ticagrelor may extend lifetime for elderly ACS patients compared with aspirin plus clopidogrel. The optimal DAPT for elderly ACS patients may be a valuable direction for future research studies.