Higher serum alanine aminotransferase levels and the incidence of hypertension: The Kailuan cohort study.

Objective: The association between serum alanine aminotransferase (ALT) concentrations and the incidence of hypertension remains unclear. To explore the association between serum ALT levels and the risk of incident hypertension based on the Kailuan cohort study. Methods: People who had participated in health check-ups in 2006-2007 without hypertension, cardiovascular, or liver diseases were enrolled and received follow-ups every two years until December 2017. Hypertension was defined as systolic blood pressure/diastolic blood pressure ≥140/90 mmHg or using anti-hypertensive medication. A multivariable-adjusted Cox regression model was used to estimate the hazard ratio (HR) and its corresponding 95 % confidence intervals (95 % CIs). Results: During 10.5 years of follow-up, 24,023 (50.7 %) participants were diagnosed with hypertension. The HR of incident hypertension was 1.02 (95 % CI=1.01-1.03) for each 10 U/L increment of ALT concentrations. Participants with elevated ALT levels (>40 U/L) had an increased incidence of hypertension by 7 % (HR =1.07; 95 % CI=1.01-1.13). Besides, the HR was 1.10 (95 % CI=1.06-1.15), 1.13 (95 % CI=1.08-1.18), and 1.22 (95 % CI=1.16-1.30) (P for trend <0.001) in (10-20], (20-30], and (30-40] groups, compared with ≤10 U/L group. In addition, participants whose ALT levels decreased to the normal range at the first follow-up had a 23 % lower incidence of hypertension than those with elevated ALT levels at baseline and the first follow-up. Conclusion: People with higher serum ALT levels may have an increased risk of incident hypertension and thus may benefit from heightened surveillance for hypertension and lifestyle interventions to reduce the risk of hypertension.

Dietary intake changes the associations between long-term exposure to fine particulate matter and the surrogate indicators of insulin resistance.

The relationship of fine particulate matter (PM2.5) exposure and insulin resistance remains inclusive. Our study aimed to investigate this association in the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). Specifically, we examined the associations between long-term PM2.5 exposure and three surrogate indicators of insulin resistance: the triglyceride-glucose index (TyG), TyG with waist circumference (TyG-WC) and metabolic score for insulin resistance (METS-IR). Additionally, we explored potential effect modification of dietary intake and components. Generalized estimating equations were used to evaluate the associations between PM2.5 and the indicators with an unbalanced repeated measurement design. Our analysis incorporated a total of 162,060 observations from 99,329 participants. Each 10 µg/m3 increment of PM2.5 was associated with an increase of 0.22 % [95 % confidence interval (CI): 0.20 %, 0.25 %], 1.60 % (95 % CI: 1.53 %, 1.67 %), and 2.05 % (95 % CI: 1.96 %, 2.14 %) in TyG, TyG-WC, and METS-IR, respectively. These associations were attenuated among participants with a healthy diet, particularly those with sufficient intake of fruit and vegetable, fish or tea (pinteraction < 0.0028). For instance, among participants with a healthy diet, TyG increased by 0.11 % (95 % CI: 0.08 %, 0.15 %) per 10 µg/m3 PM2.5 increment, significantly lower than the association observed in those with an unhealthy diet. The findings of this study emphasize the potential of a healthy diet to mitigate these associations, highlighting the urgency for improving air quality and implementing dietary interventions among susceptible populations in China.

The discovery of novel and potent indazole NLRP3 inhibitors enabled by DNA-encoded library screening.

NLRP3 is an intracellular sensor protein that detects a broad range of danger signals and environmental insults. Its activation results in a protective pro-inflammatory response designed to impair pathogens and repair tissue damage via the formation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent secretory release of the pro-inflammatory cytokines IL-1ß and IL-18 as well as to gasdermin d-mediated pyroptotic cell death. Herein, we describe the discovery of a novel indazole series of high affinity, reversible inhibitors of NLRP3 activation through screening of DNA-encoded libraries and the potent lead compound 3 (BAL-0028, IC50 = 25 nM) that was identified directly from the screen. SPR studies showed that compound 3 binds tightly (KD range 104-123 nM) to the NACHT domain of NLRP3. A CADD analysis of the interaction of compound 3 with the NLRP3 NACHT domain proposes a binding site that is distinct from those of ADP and MCC950 and includes specific site interactions. We anticipate that compound 3 (BAL-0028) and other members of this novel indazole class of neutral inhibitors will demonstrate significantly different physical, biochemical, and biological properties compared to NLRP3 inhibitors previously identified.

Value of preoperative evaluation of FEV1 in patients with destroyed lung undergoing pneumonectomy - a 20-year real-world study.

BACKGROUND: Clinical guidelines recommend a preoperative forced expiratory volume in one second (FEV1) of > 2 L as an indication for left or right pneumonectomy. This study compares the safety and long-term prognosis of pneumonectomy for destroyed lung (DL) patients with FEV1 ≤ 2 L or > 2 L. METHODS: A total of 123 DL patients who underwent pneumonectomy between November 2002 and February 2023 at the Department of Thoracic Surgery, Beijing Chest Hospital were included. Patients were sorted into two groups: the FEV1 > 2 L group (n = 30) or the FEV1 ≤ 2 L group (n = 96). Clinical characteristics and rates of mortality, complications within 30 days after surgery, long-term mortality, occurrence of residual lung infection/tuberculosis (TB), bronchopleural fistula/empyema, readmission by last follow-up visit, and modified Medical Research Council (mMRC) dyspnea scores were compared between groups. RESULTS: A total of 96.7% (119/123) of patients were successfully discharged, with 75.6% (93/123) in the FEV1 ≤ 2 L group. As compared to the FEV1 > 2 L group, the FEV1 ≤ 2 L group exhibited significantly lower proportions of males, patients with smoking histories, patients with lung cavities as revealed by chest imaging findings, and patients with lower forced vital capacity as a percentage of predicted values (FVC%pred) (P values of 0.001, 0.027, and 0.023, 0.003, respectively). No significant intergroup differences were observed in rates of mortality within 30 days after surgery, incidence of postoperative complications, long-term mortality, occurrence of residual lung infection/TB, bronchopleural fistula/empyema, mMRC ≥ 1 at the last follow-up visit, and postoperative readmission (P > 0.05). CONCLUSIONS: As most DL patients planning to undergo left/right pneumonectomy have a preoperative FEV1 ≤ 2 L, the procedure is generally safe with favourable short- and long-term prognoses for these patients. Consequently, the results of this study suggest that DL patient preoperative FEV1 > 2 L should not be utilised as an exclusion criterion for pneumonectomy.

Somatic and Germline Variants and Coronary Heart Disease in a Chinese Population.

Importance: The genetic basis of coronary heart disease (CHD) has expanded from a germline to somatic genome, including clonal hematopoiesis of indeterminate potential (CHIP). How CHIP confers CHD risk in East Asian individuals, especially those with small clones (variant allele fraction [VAF] 0.5%-2%) and different genetic backgrounds, was completely unknown. Objective: To investigate the CHIP profile in a general Chinese cohort by deep sequencing and further explore the association between CHIP and incident CHD considering germline predisposition. Design, Setting, and Participants: This cohort study used data from 3 prospective cohorts in the project Prediction for Atherosclerotic Cardiovascular Disease Risk in China. Participants without cardiovascular disease or cancer at baseline were enrolled in 2001 and 2008 and had a median follow-up of 12.17 years extending into 2021. Exposures: CHIP mutations were detected by targeted sequencing (mean depth, 916×). A predefined CHD polygenic risk score (PRS) comprising 531 variants was used to evaluate germline predisposition. Main Outcomes and Measures: The main outcome was first incident CHD. Results: Among 6181 participants, the median (IQR) age was 53.83 years (45.35-62.39 years); 3082 participants (49.9%) were female, and 3099 (50.1%) were male. A total of 1100 individuals (17.80%) harbored 1372 CHIP mutations at baseline. CHIP was independently associated with incident CHD (hazard ratio [HR], 1.42; 95% CI, 1.18-1.72; P = 2.82 × 10-4) and presented a risk gradient with increasing VAF (P = 3.98 × 10-3 for trend). Notably, individuals with small clones, nearly half of CHIP carriers, also demonstrated a higher CHD risk compared with non-CHIP carriers (HR, 1.33; 95% CI, 1.02-1.74; P = .03) and were 4 years younger than those with VAF of 2% or greater (median age, 58.52 vs 62.70 years). Heightened CHD risk was not observed among CHIP carriers with low PRS (HR, 1.02; 95% CI, 0.64-1.64; P = .92), while high PRS and CHIP jointly contributed a 2.23-fold increase in risk (95% CI, 1.51-3.29; P = 6.29 × 10-5) compared with non-CHIP carriers with low PRS. Interestingly, the diversity in CHIP-related CHD risk within each PRS group was substantially diminished when removing variants in the inflammatory pathway from the PRS. Conclusions: This study revealed that elevated CHD risk attributed to CHIP was nonnegligible even for small clones. Inflammation genes involved in CHD could aggravate or abrogate CHIP-related CHD risk.

Utilizing a novel model of PANoptosis-related genes for enhanced prognosis and immune status prediction in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is the most common histopathologic type of renal cell carcinoma. PANoptosis, a cell death pathway that involves an interplay between pyroptosis, apoptosis and necroptosis, is associated with cancer immunity and development. However, the prognostic significance of PANoptosis in KIRC remains unclear. RNA-sequencing expression and mutational profiles from 532 KIRC samples and 72 normal samples with sufficient clinical data were retrieved from the Cancer Genome Atlas (TCGA) database. A prognostic model was constructed using differentially expressed genes (DEGs) related to PANoptosis in the TCGA cohort and was validated in a Gene Expression Omnibus (GEO) cohorts. Incorporating various clinical features, the risk model remained an independent prognostic factor in multivariate analysis, and it demonstrated superior performance compared to unsupervised clustering of the 21 PANoptosis-related genes alone. Further mutational analysis showed fewer VHL and more BAP1 alterations in the high-risk group, with alterations in both genes also associated with patient prognosis. The high-risk group was characterized by an unfavorable immune microenvironment, marked by reduced levels of CD4 + T cells and natural killer cells, but increased M2 macrophages and regulatory T cells. Finally, the risk model was predictive of response to immune checkpoint blockade, as well as sensitivity to sunitinib and paclitaxel. The PANoptosis-related risk model developed in this study enables accurate prognostic prediction in KIRC patients. Its associations with the tumor immune microenvironment and drug efficacy may offer potential therapeutic targets and inform clinical decisions.

Fine Particulate Matter Exposure, Genetic Susceptibility, and the Risk of Incident Stroke: A Prospective Cohort Study.

BACKGROUND: Both genetic factors and environmental air pollution contribute to the risk of stroke. However, it is unknown whether the association between air pollution and stroke risk is influenced by the genetic susceptibilities of stroke and its risk factors. METHODS: This prospective cohort study included 40 827 Chinese adults without stroke history. Satellite-based monthly fine particulate matter (PM2.5) estimation at 1-km resolution was used for exposure assessment. Based on 534 identified genetic variants from genome-wide association studies in East Asians, we constructed 6 polygenic risk scores for stroke and its risk factors, including atrial fibrillation, blood pressure, type 2 diabetes, body mass index, and triglyceride. The Cox proportional hazards model was applied to evaluate the hazard ratios and 95% CIs for the associations of PM2.5 and polygenic risk score with incident stroke and the potential effect modifications. RESULTS: Over a median follow-up of 12.06 years, 3147 incident stroke cases were documented. Compared with the lowest quartile of PM2.5 exposure, the hazard ratio (95% CI) for stroke in the highest quartile group was 2.72 (2.42-3.06). Among individuals at high genetic risk, the relative risk of stroke was 57% (1.57; 1.40-1.76) higher than those at low genetic risk. Although no statistically significant interaction was found, participants with both the highest PM2.5 and high genetic risk showed the highest risk of stroke, with ≈4× that of the lowest PM2.5 and low genetic risk group (hazard ratio, 3.55 [95% CI, 2.84-4.44]). Similar upward gradients were observed in the risk of stroke when assessing the joint effects of PM2.5 and genetic risks of blood pressure, type 2 diabetes, body mass index, atrial fibrillation, and triglyceride. CONCLUSIONS: Long-term exposure to PM2.5 was associated with a higher risk of incident stroke across different genetic susceptibilities. Our findings highlighted the great importance of comprehensive assessment of air pollution and genetic risk in the prevention of stroke.

Genetic Predisposition, Sedentary Behavior, and Incident Coronary Artery Disease: A Prospective Chinese Cohort Study.

PURPOSE: Whether the association of sedentary behaviors with coronary artery disease (CAD) can be influenced by genetic susceptibility remains unclear. We aimed to investigate the joint and interplay effects between genetic risk and sedentary time (ST) and to further explore the extent to which the risk for CAD can be counteracted by reducing ST in different genetic groups. METHODS: This prospective cohort study included 39,164 Chinese adults without CAD history. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants, and daily ST was assessed by questionnaire. We analyzed the modification effect of genetic risk on the association of ST with CAD using the Cox proportional hazards models. RESULTS: During a median follow-up of 11.60 yr, 1156 CAD events were documented. Higher ST and PRS were separately related to elevated CAD risk. Significant additive interaction was also observed (relative excess risk due to interaction: 0.77; 95% confidence interval [CI] = 0.27-1.28). Compared with participants with low genetic risk and low ST (<6 h·d -1 ), those with high genetic risk and high ST (≥10 h·d -1 ) had the highest CAD risk, with the hazard ratio (HR) and 95% CI of 4.22 (2.65-6.71). When stratified by genetic risks, participants with high ST had gradient increment of CAD risks across low, intermediate, and high genetic risk groups, with HR (95% CI) values of 1.21 (0.61-2.40), 1.57 (1.14-2.16), and 2.15 (1.40-3.31), respectively. For the absolute risk reduction, individuals with high genetic risk achieved the greatest benefit from low ST ( Ptrend = 0.024). CONCLUSIONS: Genetic susceptibility may synergistically interact with ST to increase CAD risk. Reducing ST could attenuate the CAD risk, especially among individuals with high genetic risk.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Fruit and vegetable intake and the risk of arterial hypertension in China: A prospective cohort study.

Background: Population-based epidemiological evidence regarding the association between fruit and vegetable intake and the incidence of hypertension is inconsistent. This prospective cohort study aimed to investigate the association between fruit and vegetable intake and the risk of new-onset hypertension. Methods: Based on the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR), 58,981 Chinese adults without hypertension at baseline were included. Information on fruit and vegetable intake was collected using a food-frequency questionnaire. Cox proportional hazards models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension. Results: During 640,795 person-years of follow-up, 21,008 new cases of hypertension were recorded. Compared with participants in the lowest quintile (Q1) of total fruit and vegetable (TFV) intake, the HRs (95% CIs) of incident hypertension were 0.90 (0.86-0.95), 0.85 (0.81-0.90), 0.82 (0.78-0.86), and 0.83 (0.78-0.88) for the Q2 to Q5 group (p trend < 0.001), respectively. In further analyses categorizing participants according to the recommended intake level (500 g/day), we found that increasing the intake of TFV, even though it was still insufficient for the recommendation, also had a protective effect against the incident hypertension. When considering the intake of fruit or vegetable separately, we found similar trends as the TFV intake. Conclusion: These results suggest that a higher intake of fruit and vegetable is beneficial for preventing hypertension in Chinese adults.

Egg consumption and risk of coronary artery disease, potential amplification by high genetic susceptibility: a prospective cohort study.

BACKGROUND: Remarkable heterogeneity has been observed among population-based studies on egg consumption and risk of coronary artery disease (CAD). Whether genetic susceptibility serves as a potential explanation for this inconsistency remains unknown. OBJECTIVES: We performed a prospective cohort study to investigate the association of egg consumption with incident CAD at different genetic susceptibilities. METHODS: We included 34,111 participants without CAD at baseline from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China. Egg consumption was assessed with food frequency questionnaires. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants. The hazard ratio (HR) and 95% confidence interval (95% CI) of incident CAD associated with egg consumption and PRS were estimated using the Cox proportional hazards models. RESULTS: Over a median 11.7 y of follow-up, 1,128 incident cases of CAD were recorded. Both higher egg consumption and increased PRS were related to higher risk of CAD. When stratified by genetic risk, each increment of 3 eggs/wk was associated with a 5% higher risk of CAD for participants at low to intermediate genetic risk (HR: 1.05; 95% CI: 1.01, 1.09), whereas risk increased to HR 1.10 (95% CI: 1.05, 1.16) for those at high genetic risk; a significant synergistic interaction was also indicated at both multiplicative (Pinteraction = 0.007) and additive (relative excess risk: 0.73; 95% CI: 0.24, 1.22) scales. When the joint effect was examined, in comparison with those at low to intermediate genetic risk and consuming <1 egg/wk, the HR (95% CI) was 2.95 (2.41, 3.62) for participants with high genetic risk and consumption of ≥10 eggs/wk, and the corresponding standardized 10-y CAD rates increased from 1.37% to 4.24%. CONCLUSIONS: Genetic predisposition may synergistically interact with egg consumption in relation to increased CAD risk. PRS-stratified recommendations on egg consumption may help formulate personalized nutrition policies.

Mono- and Co-Doped Mn-Doped CsPbCl3 Perovskites with Enhanced Doping Efficiency and Photoluminescent Performance.

To investigate the effect of Mn and other metal dopants on the photoelectronic performance of CsPbCl3 perovskites, we conducted a series of theoretical analyses. Our findings showed that after Mn mono-doping, the CsPbCl3 lattice contracted and the bonding strength increased, resulting in a more compact structure of the metal octahedral cage. The relaxation of the metal octahedral cage, along with the Jahn-Teller effect, results in a decrease in lattice strain between the octahedra and a reduction in the energy of the entire lattice due to the deformation of the metal octahedron. These three factors work together to reduce intrinsic defects and enhance the stability and electronic properties of CsPbCl3 perovskites. The solubility of the Mn dopant is significantly increased when co-doped with Ni, Fe, and Co dopants, as it compensates for the lattice strain induced by Mn. Doping CsPbCl3 perovskites reduces the band gap due to the decreased contributions of 3d orbitals from the dopants. Our analyses have revealed that strengthening the CsPbCl3 lattice and reducing intrinsic defects can result in improved stability and PL properties. Moreover, increasing Mn solubility and decreasing the bandgap can enhance the PLQY of orange luminescence in CsPbCl3 perovskites. These findings offer valuable insights for the development of effective strategies to enhance the photoelectronic properties of these materials.

Effect of Air Pollution on Heart Failure: Systematic Review and Meta-Analysis.

BACKGROUND: Heart failure (HF) poses a significant global disease burden. The current evidence on the impact of air pollution on HF remains inconsistent. OBJECTIVES: We aimed to conduct a systematic review of the literature and meta-analysis to provide a more comprehensive and multiperspective assessment of the associations between short- and long-term air pollution exposure and HF from epidemiological evidences. METHODS: Three databases were searched up to 31 August 2022 for studies investigating the association between air pollutants (PM2.5, PM10, NO2, SO2, CO, O3) and HF hospitalization, incidence, or mortality. A random effects model was used to derive the risk estimations. Subgroup analysis was conducted by geographical location, age of participants, outcome, study design, covered area, the methods of exposure assessment, and the length of exposure window. Sensitivity analysis and adjustment for publication bias were performed to test the robustness of the results. RESULTS: Of 100 studies covering 20 countries worldwide, 81 were for short-term and 19 were for long-term exposure. Almost all air pollutants were adversely associated with the risk of HF in both short- and long-term exposure studies. For short-term exposures, we found the risk of HF increased by 1.8% [relative risk (RR)=1.018, 95% confidence interval (CI): 1.011, 1.025] and 1.6% (RR=1.016, 95% CI: 1.011, 1.020) per 10-µg/m3 increment of PM2.5 and PM10, respectively. HF was also significantly associated with NO2, SO2, and CO, but not O3. Positive associations were stronger when exposure was considered over the previous 2 d (lag 0-1) rather than on the day of exposure only (lag 0). For long-term exposures, there were significant associations between several air pollutants and HF with RR (95% CI) of 1.748 (1.112, 2.747) per 10-µg/m3 increment in PM2.5, 1.212 (1.010, 1.454) per 10-µg/m3 increment in PM10, and 1.204 (1.069, 1.356) per 10-ppb increment in NO2, respectively. The adverse associations of most pollutants with HF were greater in low- and middle-income countries than in high-income countries. Sensitivity analysis demonstrated the robustness of our results. DISCUSSION: Available evidence highlighted adverse associations between air pollution and HF regardless of short- and long-term exposure. Air pollution is still a prevalent public health issue globally and sustained policies and actions are called for to reduce the burden of HF. https://doi.org/10.1289/EHP11506.

Association of Long-Term Exposure to Ambient Fine Particulate Matter with Atherosclerotic Cardiovascular Disease Incidence Varies across Populations with Different Predicted Risks: The China-PAR Project.

Previous studies have established a significant link between ambient fine particulate matter (PM2.5) exposure and atherosclerotic cardiovascular disease (ASCVD) incidence, but whether this association varies across populations with different predicted ASCVD risks was uncertain previously. We included 109,374 Chinese adults without ASCVD at baseline from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. We obtained PM2.5 data of participants' residential address from 2000 to 2015 using a satellite-based spatiotemporal model. Participants were classified into low-to-medium and high-risk groups according to the ASCVD 10-year and lifetime risk prediction scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) for PM2.5 exposure-related incident ASCVD, as well as the multiplication and additive interaction, were calculated using stratified Cox proportional hazard models. The additive interaction between risk stratification and PM2.5 exposure was estimated by the synergy index (SI), the attributable proportion due to the interaction (API), and the relative excess risk due to interaction (RERI). Over the follow-up of 833,067 person-years, a total of 4230 incident ASCVD cases were identified. Each 10 µg/m3 increment of PM2.5 concentration was associated with 18% (HR: 1.18; 95% CI: 1.14-1.23) increased risk of ASCVD in the total population, and the association was more pronounced among individuals having a high predicted ASCVD risk than those having a low-to-medium risk, with the HR (95% CI) of 1.24 (1.19-1.30) and 1.11 (1.02-1.20) per 10 µg/m3 increment in PM2.5 concentration, respectively. The RERI, API, and SI were 1.22 (95% CI: 0.62-1.81), 0.22 (95% CI: 0.12-0.32), and 1.37 (95% CI: 1.16-1.63), respectively. Our findings demonstrate a significant synergistic effect on ASCVD between ASCVD risk stratification and PM2.5 exposure and highlight the potential health benefits of reducing PM2.5 exposure in Chinese, especially among those with high ASCVD risk.

Prevalence of familial hypercholesterolemia and its association with coronary artery disease: A Chinese cohort study.

Background: Familial hypercholesterolemia (FH) is underrecognized, and its association with coronary artery disease (CAD) remains limited, especially in China. We aimed to investigate the prevalence of FH and its relationship with CAD in a large Chinese cohort. Methods: FH was defined using the Make Early Diagnosis to Prevent Early Death (MEDPED) criteria. The crude and age-sex standardized prevalence of FH were calculated based on surveys of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project during 2007-2008. The associations of FH with incident CAD and its major subtypes were estimated with the cohort-stratified multivariate Cox proportional hazard models based on the data from the baseline to the last follow-up (2018-2020). Results: Among 98,885 included participants, 190 participants were defined as FH. Crude and age-sex standardized prevalence and 95% confidence interval (CI) of FH were 0.19% (0.17%-0.22%) and 0.13% (0.10%-0.16%), respectively. The prevalence varied across age groups and peaked in the group of 60-<70 years (0.28%), and the peak prevalence (0.18%) in males was earlier, yet lower than the peak crude prevalence in females (0.41%). During a mean follow-up of 10.7 years, 2493 cases of incident CAD were identified. After multivariate adjustment, FH patients had a 2.03-fold greater risk of developing CAD compared to non-FH participants. Conclusions: The prevalence of FH was estimated to be 0.19% in the participants, and it was associated with an elevated risk of incident CAD. Our study suggests that early screening of FH has certain public health significance for the prevention of CAD.

Studies on the Light-Induced Phase Transition of CsPbBr3 Metal Halide Perovskite Materials.

We investigate the internal mechanism of the light-induced phase transition of CsPbBr3 perovskite materials via density functional theory simulations. Although CsPbBr3 tends to appear in the orthorhombic structure, it can be changed easily by external stimulus. We find that the transition of photogenerated carriers plays the decisive role in this process. When the photogenerated carriers transit from the valence band maximum to conduction band minimum in the reciprocal space, they actually transit from Br ions to Pb ions in the real space, which are taken away by the Br atoms with higher electronegativity from Pb atoms during the initial formation of the CsPbBr3 lattice. The reverse transition of valence electrons leads to the weakening of bond strength, which is proved by our calculated Bader charge, electron localization function, and integral value of COHP results. This charge transition releases the distortion of the Pb-Br octahedral framework and expands the CsPbBr3 lattice, providing possibilities to the phase transition from the orthorhombic structure to tetragonal structure. This phase transition is a self-accelerating positive feedback process, increasing the light absorption efficiency of the CsPbBr3 material, which is of great significance for the widespread promotion and application of the photostriction effect. Our results are helpful to understand the performance of CsPbBr3 perovskite under a light irradiation environment.

His-Purkinje system pacing versus biventricular pacing in clinical efficacy: a systematic review and meta-analysis.

BACKGROUND: His-Purkinje system pacing (HPSP), including his-bundle pacing (HBP) and left bundle branch area pacing (LBBaP), imitates the natural conduction of the heart as an alternative to biventricular pacing (BVP) in cardiac resynchronization therapy (CRT). However, the feasibility and efficacy of HPSP were currently only evidenced by studies with a limited sample size, so this study aimed to provide a comprehensive assessment through a systematic review and meta-analysis. METHODS: In order to compare the clinical outcomes associated with HPSP and BVP in patients for CRT, PubMed, EMBASE, Cochrane Library and Web of Science database were searched from inception to April 10, 2023. Clinical outcomes of interest including QRS duration (QRSd), left ventricular (LV) function and New York Heart Association (NYHA) functional classification, pacing threshold, echocardiographic and clinical response, hospitalization rate of HF and all-cause mortality were also extracted and summarized for meta-analysis. RESULTS: A total of 13 studies (ten observational studies and three randomized studies) involving 1,121 patients were finally included. The patients were followed up for 6-27 months. Compared with BVP, CRT patients treated by HPSP presented shorter QRSd [mean difference (MD): -26.23 ms, 95% confidence interval (CI): -34.54 to -17.92, P < 0.001, I2 = 91%], greater LV functional improvement with increased left ventricular ejection fraction (LVEF) (MD: 6.01, 95% CI: 4.81 to 7.22, P < 0.001, I2 = 0%), decreased left ventricular end-diastolic dimension (LVEDD) (MD: -2.91, 95% CI: -4.86 to -0.95, P = 0.004, I2 = 35%), and more improved NYHA functional classification (MD: -0.45, 95% CI: -0.67 to -0.23, P < 0.001, I2 = 70%). In addition, HPSP was more likely to have higher echocardiographic [odds ratio (OR): 2.76, 95% CI: 1.74 to 4.39, P < 0.001, I2 = 0%], clinical (OR: 2.10, 95% CI: 1.16 to 3.80, P = 0.01, I2 = 0%) and super clinical (OR: 3.17, 95% CI: 2.09 to 4.79, P < 0.001, I2 = 0%) responses than BVP, and a lower hospitalization rate of HF (OR: 0.34, 95% CI: 0.22 to 0.51, P < 0.001, I2 = 0%), while presented no difference (OR: 0.68, 95% CI: 0.44 to 1.06, P = 0.09, I2 = 0%) in all-cause mortality compared with BVP. With threshold change taking into account, BVP was less stable than LBBaP (MD: -0.12 V, 95% CI: -0.22 to -0.03, P = 0.01, I2 = 57%), but had no difference with HBP (MD: 0.11 V, 95% CI: -0.09 to 0.31, P = 0.28, I2 = 0%). CONCLUSION: The present findings suggested that HPSP was associated with greater improvement of cardiac function in patients with indication for CRT and was a potential alternative to BVP to achieve physiological pacing through native his-purkinje system.

Beneficial effects of postoperative radiotherapy for IIIA­N2 non­small cell lung cancer after radical resection analysed using the propensity score­matching method.

The objective of the present study was to investigate the role of postoperative radiotherapy (PORT) after radical resection of stage IIIA-N2 non-small cell lung cancer (NSCLC). Subgroups of patients who benefited from PORT were evaluated. A retrospective review of 288 consecutive patients with resected pIIIA-N2 NSCLC at Beijing Chest Hospital (Beijing, China) was performed. Of these patients, 61 received PORT. The 288 patients were divided into PORT and non-PORT groups according to the treatment received. The baseline characteristics of the two patient groups were balanced using propensity score-matching (PSM; 1:1 matching). In total, 60 patients in the PORT group and 60 patients in the non-PORT group were matched. After PSM, the median survival time of the matched patients was 53 months. The 1-, 3- and 5-year overall survival (OS) rates of the PORT patient group were 95.0, 63.2 and 48.2%, respectively, while those of the non-PORT group were 86.7, 58.3 and 34.5%, respectively, and there was no significant difference between the two groups (P=0.056). The 5-year local recurrence-free survival (LRFS) rate in the PORT group was significantly improved (P=0.001). The effects of PORT on OS and LRFS rates were analysed in patients with different clinicopathological features. For subgroups with multiple N2 stations, N2 positive lymph nodes ≥4 and squamous cell carcinoma, PORT significantly increased the OS and LRFS rates (P<0.05). In conclusion, there was no statistically significant improvement in the 5-year OS rate with PORT overall, but there may be subgroups, such as patients with multiple N2 stations, N2 positive nodes ≥4 and squamous cell carcinoma histology, that could be explored as potentially benefitting from improved 5-year OS and LRFS rates with PORT.

The policy implemented by the government and the protection effect of PM2.5 decreasing on blood pressure in adolescents: From a quasi-experimental study.

Background: High particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) exposure levels posed a great risk to human health, but the protection effects of environmental protection on cardiovascular disease have not been systematically evaluated. This study aims to illustrate the effect of the decreased concentration of PM2.5 on blood pressure level in adolescents after enacting the protection measures of environment from a cohort study. Methods: A quasi-experimental study including 2415 children from the Chongqing Children's Health Cohort, aged 7.32 ± 0.60 years with normal blood pressure at baseline, with 53.94% males, were analysed. Both the generalised linear regression model (GLM) and Poisson regression model were used to calculate the impact of the declining exposure level of PM2.5 on blood pressure and the incidence of prehypertension and hypertension. Results: The annual mean PM2.5 concentration in 2014 and in 2019 were 65.01 ± 6.46 µgmes per cubic metre (µg / m3), 42.08 ± 2.04 µg / m3 respectively, and the decreased PM2.5 concentration between 2014 and 2019 was 22.92 ± 4.51 µg / m3. The effect of decreased PM2.5 concentration by 1µg / m3 on systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and the difference of blood pressure (BP) indexes between 2014 and 2019 were all significant (P < 0.001). The absolute differences of SBP (-3.598 mmHg; 95% confidence interval (CI) = -4.47,-2.72 mm Hg), DBP (-2.052 mmHg; 95% CI = -2.80,-1.31 mm Hg) and MAP (-2.568 mmHg; 95% CI = -3.27,-1.87 mm Hg) in the group with a decreased level of ≥25.56 µg / m3 were more significant than those in a decreased concentration of PM2.5 for <25.56 µg / m3 (P < 0.001). And the incidence of prehypertension and hypertension for three occasions blood pressure diagnose was 2.21% (95% CI = 1.37%-3.05%, P = 0.001) in children with PM2.5 decreased level ≤25.56 µg / m3 (50%), which was significant higher than its' counterparts 0.89% (95% CI = 0.37%-1.42%, P = 0.001). Conclusions: Our study found the etiological relationship between the declining PM2.5 concentration and the BP values and the incidence of prehypertension and hypertension in children and adolescents, suggesting continuous environmental protection measures in China have achieved remarkable health benefits.

Efficacy and safety of low levels of low-density lipoprotein cholesterol: trans-ancestry linear and non-linear Mendelian randomization analyses.

AIMS: LDL cholesterol (LDL-C) is a well-established risk factor for coronary artery disease (CAD). However, the optimal LDL-C level with regard to efficacy and safety remains unclear. We aimed to investigate the causal relationships between LDL-C and efficacy and safety outcomes. METHODS AND RESULTS: We analyzed 353 232 British from the UK Biobank and 41 271 Chinese from the China-PAR project. Linear and non-linear Mendelian randomization (MR) analyses were performed to evaluate the causal relation between genetically proxied LDL-C and CAD, all-cause mortality, and safety outcomes (including haemorrhagic stroke, diabetes mellitus, overall cancer, non-cardiovascular death, and dementia). No significant non-linear associations were observed for CAD, all-cause mortality, and safety outcomes (Cochran Q P > 0.25 in British and Chinese) with LDL-C levels above the minimum values of 50 and 20 mg/dL in British and Chinese, respectively. Linear MR analyses demonstrated a positive association of LDL-C with CAD [British: odds ratio (OR) per unit mmol/L increase, 1.75, P = 7.57 × 10-52; Chinese: OR, 2.06, P = 9.10 × 10-3]. Furthermore, stratified analyses restricted to individuals with LDL-C levels less than the guideline-recommended 70 mg/dL demonstrated lower LDL-C levels were associated with a higher risk of adverse events, including haemorrhagic stroke (British: OR, 0.72, P = 0.03) and dementia (British: OR, 0.75, P = 0.03). CONCLUSION: In British and Chinese populations, we confirmed a linear dose-response relationship of LDL-C with CAD and found potential safety concerns at low LDL-C levels, providing recommendations for monitoring adverse events in people with low LDL-C in the prevention of cardiovascular disease.

We used the Mendelian randomization method to estimate the causal relationships between LDL-C and efficacy and safety outcomes in the UK Biobank and the China-PAR project.We found a linear rather than a non-linear relationship between genetically proxied LDL cholesterol and coronary artery disease.There are potential safety concerns (including haemorrhagic stroke and dementia) for people who have low LDL-C levels.