Development of an immunoassay based on a specific antibody for the detection of diphenyl ether herbicide fomesafen.

Fomesafen belongs to the diphenyl ether herbicide, and is widely used in the control of broadleaf weeds in crop fields due to its high efficiency and good selectivity. The residual of fomesafen in soil has a toxic effect on subsequent sensitive crops and the microbial community structure because of its long residual period. Therefore, an efficient method for detecting fomesafen is critical to guide the correct and reasonable use of this herbicide. Rapid and sensitive immunoassay methods for fomesafen is unavailable due to the lack of specific antibody. In this study, a specific antibody for fomesafen was generated based on rational design of haptens and a sensitive immunoassay method was established. The half maximal inhibitory concentration (IC50) of the immunoassay was 39 ng/mL with a linear range (IC10-90) of 1.92-779.8 ng/mL. In addition, the developed assay had a good correlation with the standard UPLC-MS/MS both in the spike-recovery studies and in the detection of real soil samples. Overall, the developed indirect competitive enzyme immunoassay reported here is important for detecting and quantifying fomesafen contamination in soil and other environmental samples with good sensitivity and high reproducibility.

Establishment of an indirect competitive immunoassay for the detection of dicamba based on a highly specific nanobody.

Dicamba, a traditional highly effective and low toxicity herbicide, has gained new life with the development of dicamba-tolerant transgenic crops in recent years. However, dicamba is highly volatile and therefore easy to cause drift damage to sensitive crops. The development of efficient and sensitive detection methods is essential for monitoring of trace dicamba in the environment. Nanobody-based immunoassay plays an important role in on-site detection of pesticides. However, now rapid and sensitive immunoassay methods based on nanobody for dicamba detection were lacking. In this study, the nanobodies specifically recognizing dicamba were successfully obtained by immunising camels and phage display library construction, and then an indirect competitive immunoassay based on Nb-242 was constructed with IC50 of 0.93 µg/mL and a linear range of 0.11-8.01 µg/mL. Nb-242 had good specificity with no cross-reactivities against the dicamba analogs other than 2,3,6-trichlorobenzoic acid and the developed immnoassay had a good correlation with the standard HPLC in the spike-recovery studies. Finally, the key amino acid Ala 123, Tyr 55, Tyr 59 and Arg 72 of Nb-242 that specifically recognizing and binding with dicamba were identified by homologous modeling and molecular docking, laying an important foundation for further structural modification of Nb-242. This study has important guiding significance for constructing immunoassay method of dicamba based on nanobody and provides a sensitive, specific, and reliable detection method that is suitable for the detection of dicamba in the environment.

Estimating the impact of the outbreak of wars on financial assets: Evidence from Russia-Ukraine conflict.

This study analyzes the performance of the Shanghai Composite Index, S&P 500 index, WTI oil price, and LBMA gold price when wars took place, especially the Russia-Ukraine conflict. We employ empirical methods to explore the stability, instantaneous shock, and short-term shock regarding the abovementioned financial assets. We first adopt the event study method to ascertain whether the cumulative abnormal returns of the selected assets are significant when wars break out. Then, we use the permutation test to examine the significance of price level changes. Results show that only the Shanghai Composite Index is relatively stable. Second, the difference-in-differences model indicates that the 3 unstable assets all suffered positive shocks in their price levels within several days after the Russia-Ukraine conflict broke out. The parallel trend test confirms the validity of establishing the difference-in-differences model. Third, regression discontinuity is designed to measure the impact in a longer event window, suggesting the robustness of conclusions of the difference-in-differences model and revealing an upward trend before the conflict and a downward trend after the conflict of the financial assets. The study suggests that investors consider adjustments to investment strategies and governments take precautions to diminish the risk of the outbreak of wars.

Evaluation of phase-adjusted interventions for COVID-19 using an improved SEIR model.

A local COVID-19 outbreak with two community clusters occurred in a large industrial city, Shaoxing, China, in December 2021 after serial interventions were imposed. We aimed to understand the reason by analysing the characteristics of the outbreak and evaluating the effects of phase-adjusted interventions. Publicly available data from 7 December 2021 to 25 January 2022 were collected to analyse the epidemiological characteristics of this outbreak. The incubation period was estimated using Hamiltonian Monte Carlo method. A well-fitted extended susceptible-exposed-infectious-recovered model was used to simulate the impact of different interventions under various combination of scenarios. There were 387 SARS-CoV-2-infected cases identified, and 8.3% of them were initially diagnosed as asymptomatic cases. The estimated incubation period was 5.4 (95% CI 5.2-5.7) days for all patients. Strengthened measures of comprehensive quarantine based on tracing led to less infections and a shorter duration of epidemic. With a same period of incubation, comprehensive quarantine was more effective in containing the transmission than other interventions. Our findings reveal an important role of tracing and comprehensive quarantine in blocking community spread when a cluster occurred. Regions with tense resources can adopt home quarantine as a relatively affordable and low-impact intervention measure compared with centralized quarantine.

Global Distribution of Culex tritaeniorhynchus and Impact Factors.

Culex tritaeniorhynchus is the primary vector of Japanese encephalitis (JE) and has a wide global distribution. However, the current and future geographic distribution maps of Cx. tritaeniorhynchus in global are still incomplete. Our study aims to predict the potential distribution of Cx. tritaeniorhynchus in current and future conditions to provide a guideline for the formation and implementation of vector control strategies all over the world. We collected and screened the information on the occurrence of Cx. tritaeniorhynchus by searching the literature and online databases and used ten algorithms to investigate its global distribution and impact factors. Cx. tritaeniorhynchus had been detected in 41 countries from 5 continents. The final ensemble model (TSS = 0.864 and AUC = 0.982) indicated that human footprint was the most important factor for the occurrence of Cx. tritaeniorhynchus. The tropics and subtropics, including southeastern Asia, Central Africa, southeastern North America and eastern South America, showed high habitat suitability for Cx. tritaeniorhynchus. Cx. tritaeniorhynchus is predicted to have a wider distribution in all the continents, especially in Western Europe and South America in the future under two extreme emission scenarios (SSP5-8.5 and SSP1-2.6). Targeted strategies for the control and prevention of Cx. tritaeniorhynchus should be further strengthened.

High dose isoleucine stabilizes nuclear PTEN to suppress the proliferation of lung cancer.

PURPOSE: Cancer cells require a supply of amino acids, particularly essential amino acids such as branched-chain amino acids (BCAAs, i.e., valine, leucine, and isoleucine), to meet the increased nutrient demands of malignant tumors. The cell-autonomous and non-autonomous roles of altered BCAA supply have been implicated in cancer progression. The critical proteins involved in BCAA uptake, transport, metabolism, etc. serve as potential therapeutic biomarkers in human cancers. Here, we summarize the potential anti-tumor mechanism of BCAA by exploring the chain reaction triggered by increased BCAA supply in the tumor. METHOD: A system-wide strategy was employed to provide a generic solution to establish the links between BCAA and cancer based on comprehensive omics, molecular experimentation, and data analysis. RESULTS: BCAA over-supplementation (900 mg/kg) significantly inhibited tumor growth and reduced tumor burden, with isoleucine having the most pronounced effect. Surprisingly, isoleucine inhibited tumor growth independently of mTORC1 activation, a classical amino acid sensor. Exploratory transcriptome analysis revealed that Phosphatase and tensin homolog (PTEN) is the critical factor in the anti-tumor effect of isoleucine. By inhibiting PTEN ubiquitination, isoleucine can promote PTEN nuclear import and maintain PTEN nuclear stability. Interestingly, this process was regulated by isoleucine-tRNA ligase, cytoplasmic (IARS), a direct target of isoleucine. We demonstrated the enhanced interaction between IARS and PTEN in the presence of excess isoleucine. At the same time, IARS knockout leads to loss of isoleucine tumor suppressor ability. CONCLUSION: Overall, our results provide insights into the regulation of the IARS-PTEN anti-tumor axis by isoleucine and reveal a unique therapeutic approach based on enhancing cellular isoleucine supply.

Life expectancy and healthy life expectancy of patients with advanced schistosomiasis in Hunan Province, China.

BACKGROUND: Few studies have investigated the change in life expectancy (LE) and the healthy lifespan among patients with advanced schistosomiasis. This study was to evaluate the LE and healthy life expectancy (HLE) for patients and assess the mechanism responsible for the LE inequality. METHODS: We utilized data from a dynamic advanced schistosomiasis cohort (10,362 patients) for the period from January 2008 to December 2019 in Hunan Province, China, to calculate the LEs of patients, and made a comparison with that of general population (19,642 schistosomiasis-free individuals) in the schistosomiasis endemic areas. LEs were estimated from 15 years of age by constructing period life tables. Arriaga's decomposition method was applied to quantify the influence of the age structure on the difference in LE. HLE for advanced schistosomiasis patients was calculated by using Sullivan method with age-specific disability weight. The LE and HLE were calculated for both males and females to perform further analyses on gender gap. RESULTS: The estimated LE for advanced schistosomiasis patients aged 15-19 was 49.51 years (48.86 years for males and 51.07 years for females), which was 20.14 years lower compared with general population (69.65 years), and the LE gap between patients and general population decreased with age. The largest age-specific mortality contribution to the gap (32.06%) occurred at age 80-84 years. Women had a lower LE and HLE than men at age ≥ 60 years (both gender gaps in LE and HLE < 0). For advanced schistosomiasis patients, the gender gap in LE was largely attributed to the difference in mortality among those under the age of 55; the age-specific mortality in women exerted positive influence on the gap at age 25-64 and 75-79 years, with the contribution rate ranging from 0.59% to 57.02%, and made the negative contribution at other age groups. CONCLUSIONS: The LE of advanced schistosomiasis patients was still much lower compared with general population. Strengthened prevention strategies and targeted treatments are needed to reduce morbidity and mortality due to advanced schistosomiasis, especially for younger population and elderly female patients.

Prediction of the Risk Distributions for Anopheles sinensis, a Vector for Malaria in Shanghai, China.

Malaria is a parasitic disease caused by Plasmodium, and Anopheles sinensis is a vector of malaria. Although malaria is no longer indigenous to China, a high risk remains for local transmission of imported malaria. This study aimed to identify the risk distribution of vector An. sinensis and malaria transmission. Using data collected from routine monitoring in Shanghai from 2010 to 2020, online databases for An. sinensis and malaria, and environmental variables including climate, geography, vegetation, and hosts, we constructed 10 algorithms and developed ensemble models. The ensemble models combining multiple algorithms (An. sinensis: area under the curve [AUC] = 0.981, kappa = 0.920; malaria: AUC = 0.959, kappa = 0.800), with the best out-of-sample performance, were used to identify important environmental predictors for the risk distributions of An. sinensis and malaria transmission. For An. sinensis, the most important predictor in the ensemble model was moisture index, which reflected degree of wetness; the risk of An. sinensis decreased with higher degrees of wetness. For malaria transmission, the most important predictor in the ensemble model was the normalized differential vegetation index, which reflected vegetation cover; the risk of malaria transmission decreased with more vegetation cover. Risk levels for An. sinensis and malaria transmission for each district of Shanghai were presented; however, there was a mismatch between the risk classification maps of An. sinensis and malaria transmission. Facing the challenge of malaria transmission in Shanghai, in addition to precise An. sinensis monitoring in risk areas of malaria transmission, malaria surveillance should occur even in low-risk areas for An. sinensis.

Analysis of macro and micro freezing characteristics of gravelly soil.

To investigate the mechanism of effect of different gravel contents on freezing characteristics of gravelly soil, macroscopic and microscopic experiments were combined. Unidirectional freezing experiment and NMR experiment were conducted on gravelly soil, with gravel contents of 0%, 10%, 20%, 30%, 40% and 50%. In unidirectional freezing experiment, final temperature, stratified moisture content and frost swelling of the samples showed a parabolic pattern with an upward opening about the gravel admixture. Among that, it was at the lowest point of 30% content with the closest space between gravel and soil grains, the least consumption of heat conduction, the largest compression of water migration, making the slowest development of frost-heaving and water supply. NMR experiment results showed that freezing characteristic curve was divided into four stages of subcooling-fast-slow-stable freezing, and gravel content was proportional to the subcooling temperature and value of sudden drop of unfrozen water. Combined with the T2 spectrum, it could be seen that larger pore structure of 30% content was relatively stable with well-distributed water migration during freezing process, and order of water freezing was free water went ahead of bound water, leading to a reduction rate of water migration was from fast to slow, with a consistent pattern of the evolution rate of macro parameters. In summary, the addition of a reasonable gravel proportion in engineering applications of cold zone could ensure relatively well-distributed and stable soil properties and pore structure, and relative low difference in temperature, moisture pooling, and frost swelling. Ultimately improving the safety and reliability of the overall operation of the project.

Changing trend of sickness absenteeism among students during 2010-2017 academic years and its correlation with the incidence of acute infectious diseases in Jiading District，Shanghai / 中国学校卫生

Objective@#To describe the sickness absenteeism among primary and secondary school students in Jiading District and to analyze its correlation with the incidence of infectious diseases and associated lead or lag times, so as,to provide a scientific basis for the health and education departments to take measures.@*Methods@#The regularity and symptom composition of school sickness absenteeism among primary and secondary school students in Jiading District from the 2010-2017 were described. The Joinpoint model was applied to analyze the changing trend of absenteeism. And the rate of school sickness absenteeism and incidences of 7 acute infectious diseases were compared through visual analysis. The time lagged correlation coefficients and Granger causality tests were applied to quantitatively analyze the correlation and lead/lag patterns.@*Results@#The average rate of school sickness absenteeism among primary and secondary school students in Jiading District, Shanghai was 0.27%. Since the 2012 academic year, the overall rate of sickness absenteeism has been on the rise. Fever was the most common symptom of absenteeism (47.49%). The trend of sickness absenteeism rate was mainly consistent with the incidence of influenza, and showed a one way Granger causality. The maximum time lagged correlation coefficient was obtained in the second semester of the 2017 academic year with a value of 0.43 (95% CI =0.25-0.58). The maximum time lagged correlation coefficient between the rate of sickness absenteeism with fever and other respiratory symptoms and the incidence of influenza was also obtained in the second semester of the 2017 academic year and the maximum correlation coefficient was 0.50(95% CI =0.33-0.65).@*Conclusion@#The sickness absenteeism rate in primary and secondary school students is correlated to influenza incidence, and it has potential application value in supplementing early warning of influenza activities in the community.

Environmental Determinants for Snail Density in Dongting Lake Region: An Ecological Study Incorporating Spatial Regression.

This study explored the environmental determinants of different months on snail density measured in April at different types of snail habitats (marshlands, inner embankments, and hills) by considering spatial effects. Data were gathered from surveys on snails that were conducted in Hunan Province in April 2016, and information was collected on environmental variables. To investigate the environmental factors influencing snail density in various types of snail habitats, the ordinary least square model, spatial lag model, and spatial error model were all used. The environmental determinants for snail density showed different effects in the three types of snail habitats. In marshlands, snail density measured in April was associated positively with the normalized difference vegetation index (NDVI) and was associated negatively with flooding duration and annual hours of sunshine. Extreme temperatures correlated strongly to snail density measured in April (P < 0.05). In areas inside embankments, snail density measured in April increased with a decreased distance between snail habitat and the nearest river (P < 0.05). In hills, extreme heat, annual hours of sunshine, NDVI in September, and annual average land surface temperature (LST) were associated negatively with snail density measured in April, whereas index of moisture (IM) was associated positively with snail density measured in April (P < 0.05). The effects of LST and hours of sunshine on snail density measured in April varied with months of the year in the three different types of snail habitats (P < 0.05). Our study might provide a theoretical foundation for preventing snail transmission and subsequent spread of schistosomiasis.

Association of Daily Exposure to Air Pollutants with the Risk of Tuberculosis in Xuhui District of Shanghai, China.

Previous studies have suggested that air pollutant exposure is related to tuberculosis (TB) risk, but results have not been consistent. This study evaluated the relation between daily air pollutant exposure and TB incidence in Shanghai from 2014 to 2019. Overall, there were four pollutants that were positively related to the risk of new TB cases. After a 5 µg/m3 increase, the maximum lag-specific and cumulative relative risk (RR) of SO2 were 1.081, (95% CI: 1.035-1.129, lag: 3 days) and 1.616 (95% CI: 1.119-2.333, lag: 0-13 days), while for NO2, they were 1.061 (95% CI: 1.015-1.11, lag: 4 days) and 1.8 (95% CI: 1.113-2.91, lag: 0-15 days). As for PM2.5, with a 50 µg/m3 increase, the lag-specific and cumulative RR were 1.064 (95% CI: 1-1.132, lag: 6 days) and 3.101 (95% CI: 1.096-8.777, lag: 0-21 days), while for CO, the lag-specific RR was 1.03 (95% CI: 1.005-1.057, lag: 8 days) and the cumulative RR was 1.436 (95% CI: 1.004-2.053, lag: 0-16 days) with a 100 µg/m3 increase. The associations tended to be stronger in male and elderly patients and differed with seasons. Air pollutant exposure may be a risk factor for TB incidence.

Effects of different doses of canagliflozin on blood pressure and lipids in patients with type 2 diabetes: a meta-analysis.

BACKGROUND: Canagliflozin is a sodium glucose-cotransporter-2 receptor inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM). However, it is less prescribed due to increased LDL cholesterol (LDL-C), high incidence of urinary tract infection (UTI), high cost. Data on the effect of canagliflozin on blood pressure (BP) are also limited. We conducted a meta-analysis of randomized controlled trials (RCTs) to review dosedependent effects of canagliflozin on BP and lipids in patients with T2DM. METHODS: A meta-analysis of RCTs in patients with T2DM was conducted. MEDLINE, the Cochrane Library of Trials and Clinicaltrials.gov were searched for relevant studies from January 2008 to May 2021. RESULTS: Compared with placebo, canagliflozin 100 mg reduced SBP by 3.43 mmHg and DBP by 1.05 mmHg. Canagliflozin 100 mg increased LDL-C by 0.10mmol/l and HDL cholesterol (HDL-C) by 0.05 mmol/l. Compared with placebo, canagliflozin 300 mg reduced SBP by 4.75 mmHg and DBP by 1.69 mmHg. Canagliflozin 300 mg increased LDL-C by 0.16 mmol/l and HDL-C by 0.06 mmol/l. Compared with canagliflozin 100 mg, canagliflozin 300 mg further reduced SBP by 1.21 mmHg and DBP by 0.64 mmHg, and further increased LDL-C by 0.06 mmol/l and HDL-C by 0.02 mmol/l. Compared with placebo and canagliflozin 100 mg, canagliflozin 300 mg increased the risk of UTI. CONCLUSION: The current meta-analysis provides new evidence on different doses of canagliflozin as an antihypertensive agent in T2DM complicated by hypertension; however, LDL-C and the risk of UTI should be monitored.

Efficacy and safety of PCSK9 inhibition in cardiovascular disease: a meta-analysis of 45 randomized controlled trials.

BACKGROUND: Safety concerns about proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors make physicians reluctant to prescribe agents for patients. The present aim was to assess the efficacy and safety of alirocumab, evolocumab and bococizumab in patients with atherosclerotic cardiovascular disease (ASCVD). METHODS: Medline, the Cochrane Library and Clinicaltrials.gov were searched for 45 randomized controlled trials, involving 97,297 patients. RESULTS: Compared with the control group, PCSK9 inhibitors could significantly reduce low-density lipoprotein cholesterol, total cholesterol, triglycerides and increase high-density lipoprotein cholesterol. Alirocumab was associated with lower incidence of unstable angina (p < 0.05) and myocardial infarction (p < 0.05), compared with the control group. Alirocumab (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.60-0.97, p < 0.05), evolocumab (OR 0.79, 95% CI 0.66-0.95, p < 0.05) and bococizumab (OR 0.60, 95% CI 0.42-0.84, p < 0.05) were associated with lower incidence of stroke, compared with control group. The incidence of injection-site reactions was significantly higher in alirocumab (OR 1.68, 95% CI 1.45-1.93, p < 0.05), evolocumab (OR 1.64, 95% CI 1.41-1.91, p < 0.05) and bococizumab (OR 8.03, 95% CI 6.85-9.41, p < 0.05) group than in the control group. CONCLUSIONS: Alirocumab and evolocumab could ameliorate lipid profile and reduce the risk of cardiac disorders and stroke with satisfactory safety and tolerability. However, injection-site reactions should be paid attention to.

Interleukin-1 and Interleukin-6 Polymorphisms Might Influence Predisposition to Hemorrhagic Cerebral Vascular Diseases: A Meta-Analysis.

BACKGROUND: Interleukin-1 (IL-1) and IL-6 polymorphisms might influence predisposition to hemorrhagic cerebral vascular diseases, but the results of already published studies regarding relationship between IL-1/IL-6 polymorphisms and hemorrhagic cerebral vascular diseases were still controversial and ambiguous. OBJECTIVES: The authors designed this meta-analysis to more precisely estimate the relationship between IL-1/IL-6 polymorphisms and hemorrhagic cerebral vascular diseases by pooling the results of already published related studies. METHODS: The authors searched PubMed, EMBASE, Web of Science, and CNKI for already published studies. Eighteen already published studies were pooled analyzed in this meta-analysis. RESULTS: The pooled meta-analyses' results showed that distributions of IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms among patients and controls differed significantly. Moreover, distribution of the IL-6 rs1800795 polymorphism among patients and controls from Asians also differed significantly. Further analyses showed similar findings for IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms in aneurysmal subarachnoid hemorrhage (aSAH) subgroup. CONCLUSIONS: This meta-analysis suggested that IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms might influence susceptibility to hemorrhagic cerebral vascular diseases, especially for aSAH. Moreover, IL-6 rs1800795 might influence susceptibility to hemorrhagic cerebral vascular diseases in Asians.

Distance to highway and factory density related to lung cancer death and associated spatial heterogeneity in effects in Jiading District, Shanghai.

This study aimed to determine the spatial effects of traffic- and industrial-related pollution on the mortality for lung cancer (LC). We conducted a retrospective cohort study by using the data from LC registry in Jiading District for the period from 2002 to 2012. Standard parametric model with Weibull distribution was used for spatial survival analysis. Shorter distance to highway (adjusted odds ratio (aOR) = 1.15, 95% confidence interval (CI): 1.03-1.30) and higher factory density (aOR = 1.20, 95% CI: 1.05-1.37) were significantly associated with an increased risk of LC death, and there was a spatial difference in the associations between northern and southern areas of Jiading District. The risk was high in suburbs as compared with urban areas. Traffic- and industrial-related pollution were significantly associated with an increased risk of LC death, which showed a spatial variation. Further studies are needed to better understand the current LC status in the suburbs and to reduce health disparities.

Effects of nighttime sleep duration and sex on the association between siesta and hypertension.

OBJECTIVE: To examine the association between siesta and hypertension by sex and nighttime sleep duration among Chinese adults aged ≥35 years in Yinzhou, Ningbo City. METHODS: All data were obtained from physical examinations and structured questionnaires. A total of 44, 652 participants were included. Logistic regression models were applied to calculate odds ratios and 95% confidence intervals for the association between siesta and hypertension. RESULTS: When compared with no siesta, siesta durations of 60∼89 min (OR = 1.10, 95% CI:1.04-1.17) and ≥90 min (OR = 1.21, 95% CI:1.08-1.36) were associated with higher risk of hypertension in women. But no significant association was observed in men. Siesta durations of 30∼59 min (OR = 1.09, 95% CI:1.00-1.19) and 60-89 min (OR = 1.10, 95% CI:1.05-1.16) were associated with hypertension in people with 6∼8 h sleep, and this association appeared seemingly stronger with ≥90 min siesta either in short (<6 h) sleepers (OR = 1.20, 95% CI: 0.99-1.47) or in long (>8 h) sleepers (OR = 1.29, 95% CI: 1.00-1.68). However, in short sleepers, 60∼89 min siesta seemed to be associated with decreased risk of hypertension (OR = 0.95, 95% CI: 0.85-1.06); while in long sleepers, the same range of siesta seemed to be associated with increased risk of hypertension (OR = 1.11, 95% CI: 0.93-1.34). CONCLUSION: Long siesta was associated with increased risk of hypertension in women but not in men. Not too long siesta may be related to decreased risk of hypertension in short sleepers but not in people with adequate or even long sleep. These findings warrant further examination with prospective studies and laboratory investigations.

Geographical Variation of COPD Mortality and Related Risk Factors in Jiading District, Shanghai.

Background: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in China. Although numerous studies have been conducted to determine the risk factors for COPD mortality such as ambient air pollution, the results are not fully consistent. Methods: This study included mortality analysis and a case-control design by using the data extracted from the Mortality Registration System in Jiading District, Shanghai. Traditional logistic regression, geographically weighted logistic regression (GWLR), and spatial scan statistical analysis were performed to explore the geographic variation of COPD mortality and the possible influencing factors. Results: Traditional logistic regression showed that extreme lower temperature in the month prior to death, shorter distance to highway, lower GDP level were associated with increased COPD mortality. GWRL model further demonstrated obvious geographical discrepancies for the above associations. We additionally identified a significant cluster of low COPD mortality (OR = 0.36, P = 0.002) in the southwest region of Jiading District with a radius of 3.55 km by using the Bernoulli model. The geographical variation in age-standardized mortality rate for COPD in Jiading District was explained to a certain degree by these factors. Conclusion: The risk of COPD mortality in Jiading District showed obvious geographical variation, which were partially explained by the geographical variations in effects of the extreme low temperature in the month prior to death, residential proximity to highway, and GDP level.

Comparison of one-month versus twelve-month dual antiplatelet therapy after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome: rationale and design of prospective, multicenter, randomized, controlled IVUS-ACS and ULTIMATE-DAPT trial.

BACKGROUND: Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor. METHODS: The IVUS-ACS and ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine (1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and (2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (first randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (second randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3, or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the second randomized population. CONCLUSION: The IVUS-ACS and ULTIMATE-DAPT trial is designed to test the efficacy and safety of 2 different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients.

Effects of LCZ696 (Sacubitril/Valsartan) on Blood Pressure in Patients with Hypertension: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: LCZ696 (sacubitril/valsartan), a first-in-class angiotensin receptor-neprilysin inhibitor, can significantly reduce blood pressure in patients with heart failure. We performed this meta-analysis to determine the antihypertensive effect of LCZ696 in patients with hypertension. METHODS: Randomized controlled trials were searched in MEDLINE, the Cochrane Library, and Clinicaltrials.gov. Twelve studies with a total of 6,064 participants were included. RESULTS: Compared with angiotensin receptor blockers (ARBs), LCZ696 100 mg caused a significant reduction in systolic blood pressure (SBP) (mean difference [MD] -1.58 mm Hg, 95% confidence interval [CI] -2.09 to -1.07, p < 0.05) and diastolic blood pressure (DBP) (MD -0.66 mm Hg, 95% CI -0.98 to -0.33, p < 0.05). LCZ696 200 mg caused a significant reduction in SBP (MD -4.94 mm Hg, 95% CI -6.54 to -3.35, p < 0.05), DBP (MD -2.24 mm Hg, 95% CI -2.74 to -1.75, p < 0.05), 24-h ambulatory SBP (24 h ASBP; MD -3.69 mm Hg, 95% CI -4.80 to -2.58, p < 0.05), and 24-h ADBP (MD -1.71 mm Hg, 95% CI -2.13 to -1.28, p < 0.05). LCZ696 400 mg caused a significant reduction in SBP (MD -6.25 mm Hg, 95% CI -7.90 to -4.61, p < 0.05), DBP (MD -2.30 mm Hg, 95% CI -2.80 to -1.80, p < 0.05), 24-h ASBP (MD -4.31 mm Hg, 95% CI -6.56 to -2.07, p < 0.05), and 24 h ADBP (MD -1.69 mm Hg, 95% CI -2.59 to -0.79, p < 0.05). Compared with LCZ696 200 mg, LCZ696 400 mg caused a significant reduction in SBP (MD 1.71 mm Hg, 95% CI 1.15 to 2.27, p < 0.05), DBP (MD 0.90 mm Hg, 95% CI 0.65 to 1.16, p < 0.05), 24-h ASBP (MD 1.50 mm Hg, 95% CI 0.84 to 2.17, p < 0.05), and 24-h ADBP (MD 0.76 mm Hg, 95% CI 0.47 to 1.06, p < 0.05). CONCLUSIONS: The blood pressure-lowering effect of LCZ696 is dose-related. This meta-analysis confirms the antihypertensive effects of LCZ696.