The effect of lipid-lowering therapy on lipid-related residual risk factors: a prospective study.

BACKGROUND: Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited. METHODS: This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment. RESULTS: Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45-0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34-0.75; P < 0.001), without a significant increase of adverse reactions. CONCLUSION: Current levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.

Effect of Orem's self-care model on discharge readiness of patients undergoing enterostomy: A randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of Orem's self-care model in preparing hospitals for the discharge of patients with colorectal cancer who undergo enterostomy. METHODS: 92 patients with enterostomy were recruited between February 2022 and February 2023 from a general tertiary hospital. The participants were assigned to either the intervention group or the control group randomly. The intervention group received Orem's self-care program and a three-month follow-up, whereas the control group received only routine care and a three-month follow-up. Discharge readiness, self-care ability, and stoma-quality-of-life data were collected at hospital discharge (T1), 30 days (T2), and 90 days (T3) after discharge. RESULTS: The intervention group had substantially higher discharge readiness (knowledge, p < 0.001; coping ability, p = 0.006; personal status, p = 0.001; expected support, p = 0.021; total score, p < 0.001), better self-care ability at T1 (self-care knowledge, p < 0.001; self-care skills, p = 0.010), better total quality of life (QoL) at T1, T2, and T3 (p < 0.001; p = 0.006; p = 0.014); better stoma management and daily routine at T1 (p = 0.004; p < 0.001); and better daily routine at T2 (p = 0.009) than the control group. CONCLUSIONS: The designed discharge readiness program based on Orem's self-care could promote effective patient discharge readiness, self-care knowledge, self-care skills, and QoL. TRIAL REGISTRATION: The trial number ChiCTR2200056302 registered on ClinicalTrials.gov.

Ethylene-responsive VviERF003 modulates glycosylated monoterpenoid synthesis by upregulating VviGT14 in grapes.

Terpenoids are important contributors to the aroma of grapes and wines. Grapes contain terpenoids in both volatile free form and non-volatile glycosidic form, with the latter being more abundant. Glycosylated terpenoids are deemed as latent aromatic potentials for their essential role in adding to the flowery and fruity bouquet of wines. However, the transcriptional regulatory mechanism underlying glycosylated terpenoid biosynthesis remains poorly understood. Our prior study identified an AP2/ERF transcription factor, VviERF003, through DNA pull-down screening using the promoter of terpenoid glycosyltransferase VviGT14 gene. This study demonstrated that both genes were co-expressed and synchronized with the accumulation of glycosylated monoterpenoids during grape maturation. VviERF003 can bind to the VviGT14 promoter and promote its activity according to yeast one-hybrid and dual-luciferase assays. VviERF003 upregulated VviGT14 expression in vivo, leading to increased production of glycosylated monoterpenoids based on the evidence from overexpression or RNA interference in leaves, berry skins, and calli of grapes, as well as tomato fruits. Additionally, VviERF003 and VviGT14 expressions and glycosylated monoterpenoid levels were induced by ethylene in grapes. The findings suggest that VviERF003 is ethylene-responsive and stimulates glycosylated monoterpenoid biosynthesis through upregulating VviGT14 expression.

Indoxyl sulfate aggravates podocyte damage through the TGF-ß1/Smad/ROS signaling pathway.

INTRODUCTION: Hyperglycaemia induces the production of a large quantity of reactive oxygen species (ROS) and activates the transforming growth factor ß1(TGF-ß1)/Smad signalling pathway, which is the main initiating factor in the formation of diabetic nephropathy. Indoxyl sulfate (IS) is a protein-binding gut-derived uraemic toxin that localizes to podocytes, induces oxidative stress and inflames podocytes. The involvement of podocyte damage in diabetic nephropathy through the TGF-ß1/) signalling pathway is still unclear. METHODS: In this study, we cultured differentiated rat podocytes in vitro and measured the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a and α-SMA by quantitative real-time PCR (qRT‒PCR) and western blotting after siRNA-mediated TGF-ß1 silencing, TGF-ß1 overexpression and the presence of the ROS inhibitor acetylcysteine. We detected the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a, SRGAP2a in the Smad2/3, phosphorylated-Smad2/3 (p-Smad2/3), Smad7, NADPH oxidase 4 (NOX4), and ROS levels under high glucose (HG) and IS conditions. RESULTS: The results indicated that nephrin, synaptopodin, CD2AP and SRGAP2a expressions were significantly upregulated and α-SMA expression was significantly downregulated in the presence of HG under siRNA-mediated TGF-ß1 silencing or after the addition of acetylcysteine. However, in the presence of HG, the expressions of nephrin, synaptopodin, CD2AP and SRGAP2a were significantly downregulated, and the expression of α-SMA was significantly upregulated with the overexpression of TGF-ß1. IS supplementation under HG conditions further significantly reduced the expressions of nephrin, synaptopodin, CD2AP and SRGAP2a; altered the expressions of Smad2/3, p-Smad2/3, Smad7 and NOX4; and increased ROS production in podocytes. CONCLUSIONS: This study suggests that IS may modulate the expression of nephrin, synaptopodin, CD2AP and SRGAP2a by regulating the ROS and TGF-ß1/Smad signalling pathways, providing new theoretical support for the treatment of diabetic nephropathy.

Active Constituents with Tyrosinase Inhibitory Activities from Waste Tobacco Leaves.

One novel compound, (R)-3, 6-diethoxy-4-hydroxycyclohex-3-en-1-one (1) and thirteen known compounds were isolated from the waste tobacco leaves. The structures of two compounds (1-2) were confirmed and attributed firstly by the extensive spectroscopic data, including 1D/2D NMR, IR, HR-ESI-MS, CD, and ECD spectra. Notably, seven compounds (2, 3, 9, 10, 11, 12, and 13) exhibited better tyrosinase inhibitory activity than the positive control kojic acid. The binding modes of these compounds revealed that their structure formed strong hydrogen bonds and van der Waals forces with the active sites of tyrosinase. These results indicated that waste tobacco leaves are good resources for developing tyrosinase inhibitors.

Social Support, Resilience, and Mental Health Among Three High-Risk Groups in Hong Kong: A Mediation Analysis.

Objectives: To compare the prevalence of anxiety/depression, resilience, and social support among nurses, foreign domestic helpers (FDHs), and residents living in subdivided units (SDUs), and to examine their associations in these high-risk groups in Hong Kong during Omicron waves. Methods: We recruited 1,014 nurses, 621 FDHs, and 651 SDU residents from December 2021 to May 2022 in this cross-sectional survey. The depression, anxiety, social support, and resilience levels were measured by the validated scales. The multivariate binary logistic regression and causal mediation analysis were applied to examine the associations. Results: We observed a prevalence of 17.7% in anxiety and 21.6% in depression which were the highest in SDU residents, followed by FDHs, and lowest in nurses. Social support was associated with increased resilience levels and decreased risks of anxiety/depression. The association of social support with mental disorders was partly mediated by resilience, accounting for 30.9% and 20.9% of the total effect of social support on anxiety and depression, respectively. Conclusion: Public health strategies should target improving social support and providing resilience-promoting interventions to help reduce mental disorders in vulnerable groups.

Pollutant removal in an experimental bioretention cell situated in a northern Chinese sponge city.

To assess the viability and effectiveness of bioretention cell in enhancing rainwater resource utilization within sponge cities, this study employs field monitoring, laboratory testing, and statistical analysis to evaluate the water purification capabilities of bioretention cell. Findings indicate a marked purification impact on surface runoff, with removal efficiencies of 59.81% for suspended solids (SS), 39.01% for chemical oxygen demand (COD), 37.53% for ammonia nitrogen (NH3-N), and 30.49% for total phosphorus (TP). The treated water largely complies with rainwater reuse guidelines and tertiary sewage discharge standards. Notably, while previous research in China has emphasized water volume control in sponge city infrastructures, less attention has been given to the qualitative aspects and field-based evaluations. This research not only fills that gap but also offers valuable insights and practical implications for bioretention cell integration into sponge city development. Moreover, the methodology and outcomes of this study serve as a benchmark for future sponge city project assessments, offering guidance to relevant authorities.

An exploratory study investigating the impact of the bladder tumor microbiome on Bacillus Calmette Guerin (BCG) response in non-muscle invasive bladder cancer.

PURPOSE: Intravesical Bacillus Calmette-Guerin (BCG) is standard of care for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC). The effect of the bladder microbiome on response to BCG is unclear. We sought to characterize the microbiome of bladder tumors in BCG-responders and non-responders and identify potential mechanisms that drive treatment response. MATERIALS AND METHODS: Patients with archival pre-treatment biopsy samples (2012-2018) were identified retrospectively. Prospectively, urine and fresh tumor samples were collected from individuals with high-risk NMIBC (2020-2023). BCG response was defined as tumor-free 2 years from induction therapy. Extracted DNA was sequenced for 16S rRNA and shotgun metagenomics. Primary outcomes were species richness (α-diversity) and microbial composition (ß-diversity). Paired t-tests were performed for α-diversity (Observed species/Margalef). Statistical analysis for ß-diversity (weighted and unweighted UniFrac distances, weighted Bray-Curtis dissimilarity) were conducted through Permanova, with 999 permutations. RESULTS: Microbial species richness (P < 0.001) and composition (P = 0.001) differed between BCG responders and non-responders. Lactobacillus spp. were significantly enriched in BCG-responders. Shotgun metagenomics identified possible mechanistic pathways such as assimilatory sulfate reduction. CONCLUSION: A compositional difference exists in the tumor microbiome of BCG responders and non-responders with Lactobacillus having increased abundance in BCG responders.

Responses of leaf traits to altitude in Quercus aquifolioides and Sorbus rehderiana on the eastern edge of the Qinghai-Tibet Plateau, China.

As the most senstitive plant organs to environmental changes, leaves serve as crucial indicators of plant survival strategies. We measured the morphology, anatomical traits, gas exchange parameters, and chlorophyll fluorescence parameters of Quercus aquifolioides (evergreen broad-leaved) and Sorbus rehderiana (deciduous broad-leaved) at altitudes of 2600, 2800, 3000, 3200 and 3400 m on the eastern edge of the Qinghai-Tibet Plateau, China. We explored the similarity and difference in their responses to altitude change and the ecological adaptation strategy. The results showed that as the altitude increased, leaf dry matter content of Q. aquifolioides decreased, that of S. rehderiana increased, leaf size for both species gradually decreased, and the palisade coefficient of Q. aquifolioides showed a decreasing trend, contrasting with the increasing trend in S. rehderiana. As the altitude increased, the thickness of leaves, palisade tissue, spongy tissue, upper epidermis, and lower epidermis of both species increased significantly, with the increment of 22.4%, 4.9%, 45.1%, 23.3%, 19.6%, and 28.2%, 46.9%, 8.9%, 25.9%, 20.8% at altitude of 3400 m, respectively, compared with the altitude of 2600 m. The gas exchange and chlorophyll fluorescence parameters of S. rehderiana significantly increased with increasing altitude, while Q. aquifolioides showed the opposite trend. Leaf anatomical traits, gas exchange, and chlorophyll fluorescence parameters of both species displayed considerable plasticity. There were significant correlations among most leaf traits and between leaf traits and altitude. The survival strategy of Q. aquifolioides was more conservative in response to altitude changes, while that of S. rehderiana was more active. Both species adapted to different altitudes by adjusting their own traits.

Critical parameters to standardize the size and concentration determination of nanomaterials by nanoparticle tracking analysis.

The size and concentration are critical for the diagnostic and therapeutic applications of nanomaterials but the accurate measurement remains challenging. Nanoparticle tracking analysis (NTA) is widely used for size and concentration determination. However, highly repeatable standard operating procedures (SOPs) are absent. We adopted the "search-evaluate-test" strategy to standardize the measurement by searching the critical parameters. The particles per frame are linearly proportional to the sample concentration and the measured results are more accurate and repeatable when the concentration is 108-109 particles/ml. The optimal detection threshold is around 5. The optimal camera level is such that it allows clear observation of particles without diffractive rings and overexposure. The optimal speed is ≤ 50 in AU and âˆ¼ 10 µl/min in flow rate. We then evaluated the protocol using polydisperse polystyrene particles and we found that NTA could discriminate particles in bimodal mixtures with high size resolution but the performance on multimodal mixtures is not as good as that of resistive pulse sensing (RPS). We further analyzed the polystyrene particles, SiO2 particles, and biological samples by NTA following the SOPs. The size and concentration measured by NTA differentially varies to those determined by RPS and transmission electron microscopy.

Predictive model and risk analysis for coronary heart disease in people living with HIV using machine learning.

OBJECTIVE: This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). METHODS: Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. RESULTS: The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814-0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. CONCLUSION: This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.

[Serum folate and vitamin B12 levels and their association with neurodevelopmental features in preschool children with autism spectrum disorder]. / å­¦é¾„å‰å­¤ç‹¬ç—‡è°±ç³»éšœç¢å„¿ç«¥è¡€æ¸ å¶é ¸ã€ç»´ç”Ÿç´ B12æ°´å¹³åŠå ¶ä¸Žç¥žç»å‘è‚²ç‰¹å¾çš„å ³è”.

OBJECTIVES: To investigate the levels of serum folate and vitamin B12 (VB12) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD). METHODS: A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB12 were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment. RESULTS: The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children (P<0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients (P<0.05), and serum VB12 levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients (P<0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains (P<0.05), and serum VB12 levels were positively correlated with language developmental quotient (P<0.05). In male ASD children, serum VB12 levels were positively correlated with language and personal-social developmental quotients (P<0.05). CONCLUSIONS: Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.

Trends in the prevalence and incidence of Crohn's disease in Japan and the United States.

PURPOSE: This study is to describe patient demographic characteristics and estimate annual prevalence and incidence rates of Crohn's disease (CD) in Japan and the United States (US). METHODS: Two large employment-based healthcare claims databases (Japan Medical Data Center [JMDC] in Japan and Merative MarketScan [Merative] in the US) were used to identify patients with CD from 2010 to 2019. Cases were confirmed using an algorithm based on diagnostic with/without treatment codes. The Merative population was used for sex and age standardization of annual prevalence and incidence rates estimated from the JMDC. RESULTS: Patients with CD were generally younger in Japan than in the US at diagnosis (mean 33.6 vs. 39.4 years) and 71.5% were male versus 45.1% in the US. Annual prevalence per 100,000 population increased substantially in both countries, from 34.2 in 2010 to 54.5 in 2019 in Japan (standardized) and 163.3 to 224.2 in the US. Prevalence rates increased in both males and females in all age groups between 6 and < 65 years. Annual incidence rate per 100,000 person-years was almost fourfold higher in the US than Japan (21.0 vs. 5.5 [standardized] in 2019) but remained stable in both countries over time in both sexes and in all age groups. CONCLUSION: The epidemiology of CD differs between Japan and the US. Research to understand the basis of these differences could help to identify at-risk groups in each country, and guide implementation of preventive measures.

Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

Crucial roles of specialized chitinases in elytral and hindwing cuticles construction in Leptinotarsa decemlineata.

BACKGROUND: The Colorado potato beetle (CPB), Leptinotarsa decemlineata, is a major potato (Solanum tuberosum) pest, infesting over 16 million km2 and causing substantial economic losses. The insect cuticle forms an apical extracellular matrix (ECM) envelope covering exposed organs to direct morphogenesis and confer structural protection. While select chitinase (Cht) genes have proven essential for larval development, their potential activities directing ECM remodeling underlying adult wing maturation remain undefined. RESULTS: We investigated the expression patterns and performed an oral RNA interference (RNAi) screen targeting 19 LdChts in late-instar L. decemlineata larvae. Subsequently, we assessed their effects on adult eclosion and wing characteristics. Knockdown of LdCht5, LdCht7, LdCht10, LdIDGF2, and LdIDGF4, as well as others from Group IV (LdCht15, LdCht12, LdCht17, and LdCht13) and Groups VII-X (LdCht2, LdCht11, LdCht1, and LdCht3), resulting in shrunken, misshapen elytra with reduced areal density, as well as transverse wrinkling and impaired wing-tip folding in hindwings. Scanning electron micrographs revealed eroded elytral ridges alongside thinned, ruptured hindwing veins, indicative of mechanical fragility post-LdCht suppression. Spectroscopic analysis uncovered biomolecular alterations underlying the elytral anomalies, including decreases in peaks representing chitin, proteins, and lipids. This loss of essential ECM components provides evidence for the fragility, wrinkling, and shrinkage observed in the RNAi groups. CONCLUSION: Our findings elucidate the crucial role of chitinases in the turnover of chitinous cuticles on beetle wings, offering insights into RNAi-based control strategies against this invasive pest. © 2024 Society of Chemical Industry.

Tectorigenin protects against cardiac fibrosis in diabetic mice heart via activating the adiponectin receptor 1-mediated AMPK pathway.

Diabetic cardiomyopathy (DCM) is a common severe complication of diabetes that occurs independently of hypertension, coronary artery disease, and valvular cardiomyopathy, eventually leading to heart failure. Previous studies have reported that Tectorigenin (TEC) possesses extensive anti-inflammatory and anti-oxidative stress properties. In this present study, the impact of TEC on diabetic cardiomyopathy was examined. The model of DCM in mice was established with the combination of a high-fat diet and STZ treatment. Remarkably, TEC treatment significantly attenuated cardiac fibrosis and improved cardiac dysfunction. Concurrently, TEC was also found to mitigate hyperglycemia and hyperlipidemia in the DCM mouse. At the molecular level, TEC is involved in the activation of AMPK, both in vitro and in vivo, by enhancing its phosphorylation. This is achieved through the regulation of endothelial-mesenchymal transition via the AMPK/TGFß/Smad3 pathway. Furthermore, it was demonstrated that the level of ubiquitination of the adiponectin receptor 1 (AdipoR1) protein is associated with TEC-mediated improvement of cardiac dysfunction in DCM mice. Notably the substantial reduction of myocardial fibrosis. In conclusion, TEC improves cardiac fibrosis in DCM mice by modulating the AdipoR1/AMPK signaling pathway. These findings suggest that TEC could be an effective therapeutic agent for the treatment of diabetic cardiomyopathy.

Risk of Cardiovascular Events in Schizophrenic Patients Treated with Paliperidone Palmitate Once-Monthly Injection (PP1M): A Population-Based Retrospective Cohort Study in Taiwan.

BACKGROUND: Schizophrenia is one of the leading causes of disability. Paliperidone palmitate once-monthly injection (PP1M) was developed to provide consistent drug delivery and improve medication adherence for maintenance treatment. It is well known that patients with schizophrenia have higher cardiovascular risks, however little is known about the cardiovascular risks of patients with schizophrenia treated with PP1M in Asia. OBJECTIVE: This study aimed to estimate the incidence of cardiovascular events after initiating PP1M treatment and evaluate the cardiovascular risk associations compared with oral second-generation antipsychotics (SGAs). METHODS: Data from Taiwan's National Health Insurance Research Database were used to identify a cohort of adult patients with schizophrenia who received any SGAs from 1 March 2012 to 31 December 2018. Patients who initiated PP1M treatment were enrolled for descriptive analysis of incidence rates. PP1M patients were propensity matched 1:1 to patients initiating a new oral SGA, for comparative analysis based on demographics, clinical characteristics and treatment history at baseline, in three-step matching procedures, following the prevalent new-user design to enhance comparability. Follow-up ended at the end of the treatment episode of index drug, death, last record available, or end of the study (31 December 2019). Study endpoints included serious cardiovascular events (including severe ventricular arrhythmia and sudden death), expanded serious cardiovascular events (which further included acute myocardial infarction and ischemic stroke), and cardiovascular hospitalizations. Risks of study endpoints between matched cohorts were compared using Cox regression. RESULTS: Overall, 11,023 patients initiating PP1M treatment were identified (49.5% were females; mean age of 43.2 [12.2] years). Overall incidences for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 3.92, 7.88 and 51.96 per 1000 person-years, respectively. In matched cohort analysis (N = 10,115), the hazard ratios (HRs) between initiating PP1M and a new oral SGA for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 0.86 (95% confidence interval [CI] 0.55-1.36), 0.88 (95% CI 0.63-1.21), and 0.78 (95% CI 0.69-0.89), respectively. CONCLUSION: This study reported the population-based incidence of cardiovascular events in schizophrenic patients initiating PP1M treatment. PP1M was not associated with increased risks of serious cardiovascular events but was potentially associated with lower risks of cardiovascular hospitalizations compared with oral SGAs.

[Effects of thinning on accumulation of soil microbial residue carbon of Picea asperata plantations in sub-alpine region of western Sichuan, China]. / 间伐对川西亚高山云杉人工林土壤微生物残体碳积累的影响.

Microbial residues are an important component of soil organic carbon (SOC). It is unclear how long-term thinning affects the accumulation characteristics of microbial residue carbon (C). We analyzed the differences in soil physicochemical properties, microbial communities, extracellular enzyme activities, and microbial residue C in topsoil (0-10 cm) and subsoil (20-30 cm) in Picea asperata plantation of non-thinned (control, 4950 trees·hm-2) and thinned for 14 years (1160 trees·hm-2) stands, aiming to reveal the regulatory mechanism of thinning on microbial residue C accumulation. The results showed that thinning significantly increased SOC content, total nitrogen content, available phosphorus content, the proportion of particulate organic C, soil water content, C-cycle hydrolase, and acid phosphatase activities, but significantly reduced the proportion of mineral-associated organic C. Thinning significantly affected the content of fungal and microbial residue C, and the contribution of microbial residue C to SOC, and these effects were independent of soil layer. The content of fungal and microbial residue C was 25.0% and 24.5% higher under thinning treatments. However, thinning significantly decreased the contribution of microbial residue C to SOC by 12.3%, indicating an increase in the proportion of plant-derived C in SOC. Stepwise regression analysis showed that total nitrogen and soil water content were key factors influencing fungal and micro-bial residue C accumulation. In summary, thinning promoted microbial residue C sequestration by altering soil pro-perties and changed the composition of SOC sources.

Multi-step validation of a deep learning-based system with visual explanations for optical diagnosis of polyps with advanced features.

Artificial intelligence (AI) has been found to assist in optical differentiation of hyperplastic and adenomatous colorectal polyps. We investigated whether AI can improve the accuracy of endoscopists' optical diagnosis of polyps with advanced features. We introduced our AI system distinguishing polyps with advanced features with more than 0.870 of accuracy in the internal and external validation datasets. All 19 endoscopists with different levels showed significantly lower diagnostic accuracy (0.410-0.580) than the AI. Prospective randomized controlled study involving 120 endoscopists into optical diagnosis of polyps with advanced features with or without AI demonstration identified that AI improved endoscopists' proportion of polyps with advanced features correctly sent for histological examination (0.960 versus 0.840, p < 0.001), and the proportion of polyps without advanced features resected and discarded (0.490 versus 0.380, p = 0.007). We thus developed an AI technique that significantly increases the accuracy of colorectal polyps with advanced features.

Effects of paternal ionizing radiation exposure on fertility and offspring's health.

Purpose: The intergenerational effects of ionizing radiation remain controversial. Extensive insights have been revealed for DNA mutations and cancer incidence in progeny, yet many of these results were obtained by immediate post-radiation mating. However, conception at short times after radiation exposure is likely to be avoided. After a long period of fertility recovery, whether unexposed sperm derived from exposed spermatogonia would challenge the health of the offspring is not yet clearly demonstrated. Methods: Ten-week-old C57BL/6J males underwent whole-body acute γ irradiation at 0 and 6.4 Gy. Testes and sperm were collected at different times after radiation to examine reproductive changes. The reproductive, metabolic, and neurodevelopmental parameters were measured in the offspring of controls and the offspring derived from irradiated undifferentiated spermatogonia. Results: Paternal fertility was lost after acute 6.4 Gy γ radiation and recovered at 10-11 weeks post irradiation in mice. The reproductive, metabolic, and neurodevelopmental health of offspring born to irradiated undifferentiated spermatogonia were comparable to those of controls. Conclusion: The male mice could have healthy offspring after recovery from the damage caused by ionizing radiation.