Independent and joint associations of monocyte to high-density lipoprotein-cholesterol ratio and body mass index with cardiorenal syndrome: insights from NHANES 2003-2020.

BACKGROUND: With the development of pathophysiology, cardiorenal syndrome (CRS), a complex and severe disease, has received increasing attention. Monocyte to high-density lipoprotein-cholesterol ratio (MHR) and body mass index (BMI) are independent risk factors for cardiovascular diseases, but their association with CRS remains unexplored. This study aims to explore the independent and joint effects of MHR and BMI on CRS. METHODS: We included 42,178 NHANES participants. The determination of CRS referred to the simultaneous presence of cardiovascular disease (identified through self-report) and chronic kidney disease (eGFR < 60 mL/min per 1.73 m²). We employed multivariate weighted logistic regression to evaluate the odds ratio (OR) and 95% confidence interval (CI) for the independent and joint associations of MHR and BMI with CRS. We also conducted restricted cubic spines to explore nonlinear associations. RESULTS: The prevalence of CRS was 3.45% among all participants. An increase in both MHR and BMI is associated with a higher risk of CRS (MHR: OR = 1.799, 95% CI = 1.520-2.129, P < 0.001, P-trend < 0.001; BMI: OR = 1.037, 95% CI = 1.023-1.051, P < 0.001). Individuals who simultaneously fall into the highest quartile of MHR and have a BMI of 30 or more face the highest risk of CRS compared to those in the lowest MHR quartile with a BMI of less than 25 (OR = 3.45, 95% CI = 2.40-4.98, P < 0.001). However, there is no interactive association between MHR and BMI with CRS. CONCLUSIONS: Higher MHR and BMI are associated with higher odds of CRS. MHR and BMI can serve as tools for early prevention and intervention of CRS, respectively.

Desipramine ameliorates fine particulate matter-induced hepatic insulin resistance by modulating the ceramide metabolism in mice.

Recent research has highlighted a correlation between exposure to ambient fine particulate matter (PM2.5) and the development of systemic insulin resistance (IR) along with an elevated risk of diabetes. Ceramide has emerged as one of the pathogenic mechanisms contributing to IR. The inhibition of acid sphingomyelinase (ASMase) activity by desipramine (DES) has been shown to effectively reduce ceramide levels. In the present study, 24 female C57BL/6 N mice were randomized into one of the four groups: the filtered air exposure (FA) group, the concentrated PM2.5 exposure (PM) group, the concentrated PM2.5 treated with low-dose DES (DL) group, and the concentrated PM2.5 treated with high-dose DES (DH) group. The PM, DL and DH groups were exposed to PM2.5 for an 8-week period within a whole-body exposure system. The study encompassed extensive examinations of glucose homeostasis, liver lipid profile, ceramide pathway, and insulin signaling pathway. Our results demonstrated that PM2.5 exposure caused impaired glucose tolerance, elevated ceramide levels, increased phosphorylation PP2A, reduced Akt phosphorylation, and hindered GLUT2 expression. Remarkably, DES administration mitigated PM2.5-induced IR by effectively lowering ceramide levels. In conclusion, the reduction of ceramide levels by DES may be a promising therapeutic strategy for coping PM2.5-induced IR.

Exposure memory and susceptibility to ambient PM2.5: A perspective from hepatic cholesterol and bile acid metabolism.

Both epidemiological and experimental studies increasingly show that exposure to ambient fine particulate matter (PM2.5) is related to the occurrence and development of chronic diseases, such as metabolic diseases. However, whether PM2.5 has "exposure memory" and how these memories affect chronic disease development like hepatic metabolic homeostasis are unknown. Therefore, we aimed to explore the effects of exposure transition on liver cholesterol and bile acids (BAs) metabolism in mice. In this study, C57BL/6 mice were exposed to concentrated ambient PM2.5 or filtered air (FA) in a whole-body exposure facility for an initial period of 10 weeks, followed by another 8 weeks of exposure switch (PM2.5 to FA and FA to PM2.5) comparing to non-switch groups (FA to FA and PM2.5 to PM2.5), which were finally divided into four groups (FF of FA to FA, PP of PM2.5 to PM2.5, PF of PM2.5 to FA, and FP of FA to PM2.5). Our results showed no significant difference in food intake, body composition, glucose homeostasis, and lipid metabolism between FA and PM2.5 groups after the initial exposure before the exposure switch. At the end of the exposure switch, the mice switched from FA to PM2.5 exposure exhibited a high sensitivity to late-onset PM2.5 exposure, as indicated by significantly elevated hepatic cholesterol levels and disturbed BAs metabolism. However, the mice switched from PM2.5 to FA exposure retained a certain memorial effects of previous PM2.5 exposure in hepatic cholesterol levels, cholesterol metabolism, and BAs metabolism. Furthermore, 18-week PM2.5 exposure significantly increased hepatic free BAs levels, which were completely reversed by the FA exposure switch. Finally, the changes in small heterodimeric partner (SHP) and nuclear receptor subfamily 5 group A member 2 (LRH1) in response to exposure switch mechanistically explained the above alterations. Therefore, mice switching from PM2.5 exposure to FA showed only a weak memory of prior PM2.5 exposure. In contrast, the early FA caused mice to be more susceptible to subsequent PM2.5 exposure.

PM2.5-induced cellular senescence drives brown adipose tissue impairment in middle-aged mice.

Airborne fine particulate matter (PM2.5) exposure is closely associated with metabolic disturbance, in which brown adipose tissue (BAT) is one of the main contributing organs. However, knowledge of the phenotype and mechanism of PM2.5 exposure-impaired BAT is quite limited. In the study, male C57BL/6 mice at three different life phases (young, adult, and middle-aged) were simultaneously exposed to concentrated ambient PM2.5 or filtered air for 8 weeks using a whole-body inhalational exposure system. H&E staining and high-resolution respirometry were used to assess the size of adipocytes and mitochondrial function. Transcriptomics was performed to determine the differentially expressed genes in BAT. Quantitative RT-PCR, immunohistochemistry staining, and immunoblots were performed to verify the transcriptomics and explore the mechanism for BAT mitochondrial dysfunction. Firstly, PM2.5 exposure caused altered BAT morphology and mitochondrial dysfunction in middle-aged but not young or adult mice. Furthermore, PM2.5 exposure increased cellular senescence in BAT of middle-aged mice, accompanied by cell cycle arrest, impaired DNA replication, and inhibited AKT signaling pathway. Moreover, PM2.5 exposure disrupted apoptosis and autophagy homeostasis in BAT of middle-aged mice. Therefore, BAT in middle-aged mice was more vulnerable to PM2.5 exposure, and the cellular senescence-initiated apoptosis, autophagy, and mitochondrial dysfunction may be the mechanism of PM2.5 exposure-induced BAT impairment.

Metabolic Profile and Lipid Metabolism Phenotype in Mice with Conditional Deletion of Hepatic BMAL1.

The disruption of circadian rhythms (CRs) has been linked to metabolic disorders, yet the role of hepatic BMAL1, a key circadian regulator, in the whole-body metabolism and the associated lipid metabolic phenotype in the liver remains unclear. Bmal1 floxed (Bmal1f/f) and hepatocyte-specific Bmal1 knockout (Bmal1hep-/-) C57BL/6J mice underwent a regular feeding regimen. Hepatic CR, lipid content, mitochondrial function, and systemic metabolism were assessed at zeitgeber time (ZT) 0 and ZT12. Relevant molecules were examined to elucidate the metabolic phenotype. Hepatocyte-specific knockout of Bmal1 disrupted the expression of rhythmic genes in the liver. Bmal1hep-/- mice exhibited decreased hepatic TG content at ZT0, primarily due to enhanced lipolysis, reduced lipogenesis, and diminished lipid uptake. The ß-oxidation function of liver mitochondria decreased at both ZT0 and ZT12. Our findings on the metabolic profile and associated hepatic lipid metabolism in the absence of Bmal1 in hepatocytes provides new insights into metabolic syndromes from the perspective of liver CR disturbances.

The effect and safety of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: With the escalating social pressures, there has been a continuous rise in the prevalence of depression among the population, leading to substantial healthcare burdens. Moreover, conventional pharmacological interventions still exhibit certain limitations. Therefore, the primary objective of this study is to systematically evaluate the clinical efficacy of probiotics in the treatment of depression. METHODS: Randomized controlled trials of probiotics in treating depressive symptoms were retrieved from Pubmed, Cochrane Library, Web of Science, Wan Fang database, and CNKI between the establishment of the database and March 2022. The primary outcome was Beck's depression rating scale (BDI) scores, while the secondary outcomes were depression scores on the DASS-21 scale, biochemical indicators (IL-6, NO, and TNF-α levels), and adverse events. In addition, Revman 5.3 was used for Meta-analysis and quality evaluation, and Stata 17 was used for the Egger test and Begg's test. A total of 776 patients, including 397 and 379 patients in the experimental and control groups, respectively, were included. RESULTS: The total BDI score of the experimental group was lower than that of the control group (MD = - 1.98, 95%CI - 3.14 to - 0.82), and the score of DASS (MD = 0.90, 95%CI - 1.17 to 2.98), the IL-6 level (SMD = - 0.55, 95%CI - 0.88 to - 0.23), the NO level (MD = 5.27, 95% CI 2.51 to 8.03), and the TNF-α level (SMD = 0.19, 95% CI - 0.25 to 0.63). CONCLUSION: The findings substantiate the therapeutic potential of probiotics in mitigating depressive symptoms by significantly reducing Beck's Depression Inventory (BDI) scores and alleviating the overall manifestation of depression.

Frailty index trajectories in Chinese older adults with diverse levels of social participation: findings from a national population-based longitudinal study.

BACKGROUND: Aging and frailty pose significant challenges globally, placing a substantial burden on healthcare and social services due to their adverse consequences. AIM: The primary objective of this study was to investigate the relationship between social participation and development of frailty transition and trajectory. METHODS: This study utilized data from the CLHLS Cohort, a 10-year follow-up study involving 6713 participants, to investigate the association between social participation and development of frailty. Frailty reflects a comprehensive decline in various body functions. The study employed a group-based trajectory model to analyze the development trajectory of the frailty index and used logistic regression to assess the odds ratio (OR) of frailty risk. RESULTS: We identified two distinct groups of frailty progression trajectories: the "stable development group" and the "rapid growth group." Individuals who engaged in social activities at least once a month, but not daily, exhibited a significant association with an increased risk of transitioning into the "rapid growth group" (OR 1.305, 95% CI 1.032-1.649). Those with social participation less than once a month had an even greater risk (OR 1.872, 95% CI 1.423-2.463). Moreover, low social participation frequency (occasionally/never) has a more pronounced impact on frailty progression in males. CONCLUSION: A higher frequency of social participation is associated with a lower risk of being classified into the "rapid growth group" and a slower rate of frailty index progression. Preventing the progression of frailty can contribute to enhanced support for healthy aging among older adults.

Heavy metal risk of disposable food containers on human health.

The consumption of disposable materials is booming with the rapid development of urbanization and industrialization, which may inevitably cause the release of toxic and harmful substances during use of them in daily life. This study was to estimate element levels such as Beryllium (Be), Vanadium (V), Zinc (Zn), Manganese (Mn), Cadmium (Cd), Chromium (Cr), Nickel (Ni), Cobalt (Co), Antimony (Sb), Barium (Ba), Lead (Pb), Iron (Fe), Copper (Cu), and Selenium (Se) in leachate and subsequently assess the health risk of exposure to those disposable products such as paper and plastic food containers. We found that a large amount of metals was released from disposable food containers in hot water, and the order of metal concentration is Zn > Ba > Fe > Mn > Ni > Cu > Sb > Cr > Se > Be > Pb > Co > V > Cd. Additionally, the hazard quotient (HQ) of metals in young adults were less than 1, and were decreased in the order of Sb > Fe > Cu > Be > Ni > Cr > Pb > Zn > Se > Cd > Ba > Mn > V > Co. Furthermore, the excess lifetime cancer risk (ELCR) results of Ni and Be indicated that chronic exposure to Ni and Be may have a non-negligible carcinogenic risk. These findings suggest that potential health risk of metals may exist for the individuals to use disposable food containers under high temperature environment.

Hawthorn total flavonoids ameliorate ambient fine particulate matter-induced insulin resistance and metabolic abnormalities of lipids in mice.

Recent studies have shown a strong correlation between ambient fine particulate matter (PM2.5) exposure and diabetes risk, including abnormal lipid accumulation and systemic insulin resistance (IR). Hawthorn total flavonoids (HF) are the main groups of active substances in Hawthorn, which showed anti-hyperlipidemic and anti-hyperglycemic effects. Therefore, we hypothesized that HF may attenuate PM2.5-induced IR and abnormal lipid accumulation. Female C57BL/6 N mice were randomly assigned to the filtered air exposure (FA) group, concentrated PM2.5 exposure (PM) group, PM2.5 exposure maintained on a low-dose HF diet (LHF) group, and PM2.5 exposure maintained on a high-dose HF diet (HHF) group for an 8-week PM2.5 exposure using a whole-body exposure device. Body glucose homeostasis, lipid profiles in the liver and serum, and enzymes responsible for hepatic lipid metabolism were measured. We found that exposure to PM2.5 impaired glucose tolerance and insulin sensitivity. In addition, triacylglycerol (TAG) in serum elevated, whereas hepatic TAG levels were decreased after PM2.5 exposure, accompanied by inhibited fatty acid uptake, lipogenesis, and lipolysis in the liver. HF administration, on the other hand, balanced the hepatic TAG levels by increasing fatty acid uptake and decreasing lipid export, leading to alleviated systemic IR and hyperlipidemia in PM2.5-exposed mice. Therefore, HF administration may be an effective strategy to protect against PM2.5-induced IR and metabolic abnormalities of lipids.

PM2.5 increases mouse blood pressure by activating toll-like receptor 3.

BACKGROUND AND AIMS: Plenty of literature has documented that fine particulate matter (PM2.5) exposure is related to blood pressure (BP) elevation. Vascular dysfunction is the initiation of cardiovascular diseases, such as hypertension. This thesis set out to assess the role of Toll-like receptor 3 (TLR3) in the increase in BP induced by PM2.5. METHODS: C57BL/6 and TLR3 deficient (TLR3-/-) male mice were randomly allocated to filtered air chamber or real-world inhaled concentrated PM2.5 chamber. BP was evaluated using non-invasive BP recordings. After euthanasia, the aortas and small mesenteric arteries (SMAs) were isolated, and vascular tone was measured using a wire myograph. Leucocytes were detached to assess myeloid-derived suppressor cells using flow cytometry. siRNA transfection was performed to silence TLR3 expression in the human vascular endothelial cells incubated with PM2.5. The gene expression levels of inflammation, adhesion molecules, and oxidative stress in the aortas were assessed by quantitative PCR. RESULTS: Exposure to PM2.5 increased mouse BP, and TLR3 deficiency protected against PM2.5 exposure-induced BP increase. Additionally, the injury of vascular function in the aortas and SMAs was inhibited in TLR3-/- mice. The intercellular adhesion molecule-1 (ICAM-1) was attenuated in TLR3-/- mice, accompanied by the inhibition of inflammatory and oxidized genes of the aortas, such as F4/80, interleukin-6, interleukin-1 beta, and NADPH oxidase 4. In vitro, the enhanced mRNA expression of genes encoding inflammation, oxidative stress, and ICAM-1 by PM2.5 was inhibited by TLR3 silence as well. CONCLUSIONS: PM2.5 exposure increased BP via TLR3 activation and impaired vascular function.

Ambient fine particulate matter exposure disrupts placental autophagy and fetal development in gestational mice.

Recent studies have shown that some adverse pregnancy outcomes, especially intrauterine growth restriction (IUGR), are associated with gestational exposure to ambient fine particulate matter (PM2.5). However, potential mechanism remains to be elucidated. In the present study, pregnant C57BL/6 mice were randomly assigned to be exposed to either filtered air or ambient PM2.5 in the gestation period via a concentrated whole-body exposure system. We found that gestational PM2.5 exposure exerted no effect on implantation, preterm delivery, as well as fetal resorption and death. However, in utero fetal exposure to PM2.5 showed a significant reduction in body weight and crown-rump length on GD13 and GD18. Meanwhile, maternal blood sinusoid in placenta was markedly reduced along with abnormal expression of placental nutrient transporters and growth hormone in dams exposed to PM2.5. Additional tests showed gestational PM2.5 exposure decreased autophagy-related protein levels and inhibited autophagy flux mainly on GD15. Correspondingly, AMPK/mTOR signaling pathway, a critical negative regulator of autophagy, was activated in placenta on GD15 by PM2.5 exposure as well. These findings provide evidences that placental developmental disorder caused by autophagy inhibition might be an important mechanism for the growth restriction caused by PM2.5 exposure.

Ambient fine particulate matter exposure disrupts circadian rhythm and oscillation of the HPA axis in a mouse model.

Emerging evidence supports that exposure to ambient fine particulate matter (PM2.5) is associated with the metabolic syndrome. As the main neuroendocrine axis in mammals, the hypothalamic-pituitary-adrenal (HPA) axis's circadian rhythm (CR) plays an essential role in regulating metabolic homeostasis. Our previous studies found that ambient PM2.5 exposure caused CR disorder of the critical enzymes involved in lipid metabolism in mouse liver and adipose tissues. However, the impact of ambient PM2.5 exposure on the HPA axis is not fully illustrated yet. Male C57BL/6 mice were randomly exposed to ambient PM2.5 or filtered air for ten weeks via a whole-body exposure system. Rhythmic oscillations of clock genes in the hypothalamus and adrenal gland were characterized. The effects of ambient PM2.5 exposure on clock gene expression and rhythmic expression of molecules related to glucocorticoid synthesis were also examined. Firstly, a more robust CR of clock genes was demonstrated in the adrenal gland than that in the hypothalamus. Secondly, PM2.5 exposure significantly inhibited the expression of Clock at ZT8 in the hypothalamus. However, both circadian oscillation and expression levels of Bmal1, Cry1, Cry2, and Rorα were increased significantly by ambient PM2.5 exposure in the adrenal gland. Moreover, abnormal rhythmic oscillation patterns of corticotropin-releasing hormone and adrenocorticotropic hormone were observed after ambient PM2.5 exposure, with no change at the expression levels. Finally, the expression of Cyp11b1 was markedly decreased at ZT0 in the adrenal gland of PM2.5 exposed mice. Our findings provide new insights into the ambient PM2.5 exposure-induced metabolic syndrome from the perspective of CR disturbances.

[Meta-analysis and systematic review of efficacy and safety of Lianhua Qingwen in adjuvant treatment of adult pneumonia].

To systematically evaluate the clinical efficacy and safety of Lianhua Qingwen in the treatment of adult pneumonia. The randomized controlled trial of Lianhua Qingwen combined with conventional Western medicine in the treatment of pneumonia were retrieved from PubMed, EMbase, Wanfang database, VIP database, and CNKI from the establishment of database to March 2020. Two researchers independently conducted literature screening and data extraction, and the third researcher was in charge of arbitration in case of any disagreement. Outcome indicators included total clinical effective rate, symptom improvement time, and incidence of adverse events. R 3.6.1 was used for Meta-analysis, and RevMan 5.3 was used for quality evaluation. Twenty-two studies were included, with a total of 2 007 patients, including 1 017 patients in the experimental group and 990 patients in the control group. The results showed that the total clinical effective rate of the experimental group was higher than that of the control group(RR=1.11, 95%CI[1.08, 1.15], P<0.001), and the antifebrile time(MD=-1.81, 95%CI[-2.42,-1.21], P<0.001), cough duration(MD=-2.32, 95%CI[-2.89,-1.76], P<0.001), rale duration(MD=-2.19, 95%CI[-2.74,-1.63], P<0.001), imaging recovery time(MD=-2.17, 95%CI[-2.76,-1.58], P<0.001) and post-treatment CRP(MD=-4.07, 95%CI[-6.39,-1.75], P<0.001] were all significantly lower than those of the control group. However, it did not proved that the experimental group was safer than the control group(RR=0.84, 95%CI[0.57, 1.24], P=0.382). The results confirmed that Lianhua Qingwen combined with conventional Western medicine in the treatment of pneumonia could improve the clinical treatment efficiency, shorten the time of fever, cough, rale disappearance and imaging recovery, improve CRP index and accelerate the recovery of pneumonia patients. However, the literatures included in this study had a low quality, and the conclusions still need to be further confirmed by more high-quality, multi-center, rigorously designed randomized controlled trial.

Sex-dependent effects of ambient PM2.5 pollution on insulin sensitivity and hepatic lipid metabolism in mice.

BACKGROUND & AIMS: Emerging evidence supports ambient fine particulate matter (PM2.5) exposure is associated with insulin resistance (IR) and hepatic lipid accumulation. In this study, we aimed to evaluate the sex-dependent vulnerability in response to PM2.5 exposure and investigate the underlying mechanism by which PM2.5 modulates hepatic lipid metabolism. METHODS: Both male and female C57BL/6 mice were randomly assigned to ambient PM2.5 or filtered air for 24 weeks via a whole body exposure system. High-coverage quantitative lipidomics approaches and liquid chromatography-mass spectrometry techniques were performed to measure hepatic metabolites and hormones in plasma. Metabolic studies, histological analyses, as well as gene expression levels and molecular signal transduction analysis were applied to examine the effects and mechanisms by which PM2.5 exposure-induced metabolic disorder. RESULTS: Female mice were more susceptible than their male counterparts to ambient PM2.5 exposure-induced IR and hepatic lipid accumulation. The hepatic lipid profile was changed in response to ambient PM2.5 exposure. Levels of hepatic triacylglycerols (TAGs), free fatty acids (FFAs) and cholesterol were only increased in female mice from PM group compared to control group. Plasmalogens were dysregulated in the liver from PM2.5-exposed mice as well. In addition, exposure to PM2.5 led to enhanced hepatic ApoB and microsomal triglyceride transport protein expression in female mice. Finally, PM2.5 exposure inhibited hypothalamus-pituitary-adrenal (HPA) axis and decreased glucocorticoids levels, which may contribute to the vulnerability in PM2.5-induced metabolic dysfunction. CONCLUSIONS: Ambient PM2.5 exposure inhibited HPA axis and demonstrated sex-associated differences in its effects on IR and disorder of hepatic lipid metabolism. These findings provide new mechanistic evidence of hormone regulation in air pollution-mediated metabolic abnormalities of lipids and more personalized care should be considered in terms of sex-specific risk factors.

Association between depressive symptoms and cognitive function in the older population, and the mediating role of neurofilament light chain: Evidence from NHANES 2013-2014.

OBJECTIVE: This study aimed to investigate the potential mediating role of the neurofilament light chain (NfL) level between depressive symptoms and cognitive function in older population. METHODS: A total of 495 adults (age ≥60 years) from the National Health and Nutrition Examination Survey (NHANES) participated in this study. Cognitive function was assessed using a combination of the Animal Fluency Test (AFT), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and the Digit Symbol Substitution Test (DSST). Word List Learning Test. Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms. Data on serum NfL(sNfL) were collected. Multiple linear regressions and mediation analysis were utilized to examine the associations. RESULTS: After adjusting for potential confounding factors, the proportions mediated by the sNfL level between depressive symptoms and cognitive function was 19.65 %. The indirect effect mediated by the sNfL level between depressive symptoms and cognitive function was significant (ß[95 % CI]:-0.0089 [-0.0191, -0.0017],p = 0.040), while the direct effect in the absence of sNfL was non-significant (ß[95 % CI]: -0.0365 [-0.0739 0.0008],p = 0.055). LIMITATIONS: This is an explorative cross-sectional study with its limits in generalizability and ability to establish definitive causal associations. The results should be interpreted with caution due to the constraints imposed by the characteristics of the population with a relatively low overall level of depressive symptoms. CONCLUSION: The sNfL level, depressive symptoms, and cognitive decline are interconnected, and the sNfL level could mediate the relationship between depressive symptoms and cognitive decline among older adults.

Long-term impact of PM2.5 exposure on frailty, chronic diseases, and multimorbidity among middle-aged and older adults: insights from a national population-based longitudinal study.

Particulate Matter 2.5 (PM2.5) is a significant risk factor for frailty and chronic diseases. Studies on the associations between PM2.5 and frailty, chronic diseases, and multimorbidity are scarce, especially from large cohort studies. We aimed to explore the potential association between PM2.5 exposure and the risk of frailty, chronic diseases, and multimorbidity. We collected data from a national cohort (CHARLS) with a follow-up period of 11-18 years, totaling 13,366 participants. We obtained PM2.5 concentration data from the Atmospheric Composition Analysis Group at Dalhousie University. PM2.5 exposure is based on the average annual concentration in the prefecture-level city where residents live. We define frailty as the comprehensive manifestation of declining various body functions, characterized by a frailty index of 0.25 or greater, and multimorbidity as the presence of at least two or more chronic conditions. Cox proportional hazards regression was used to estimate the hazard ratio (HR) with its 95% confidence interval (95%CI). A 10-µg/m3 increase for PM2.5 was significantly associated with an increased risk of frailty (HR = 1.289, 95%CI = 1.257-1.322, P < 0.001). A 10-µg/m3 increase for PM2.5 was significantly associated with the elevated risk for most chronic diseases. Compared to those with no morbidity or only single morbidity, a 10-µg/m3 increase for PM2.5 was significantly associated with the elevated risk for multimorbidity (HR = 1.220, 95%CI = 1.181-1.260, P < 0.001). Ambient PM2.5 exposure is a significant risk factor for frailty, chronic diseases, and multimorbidity, and some measures need to be taken to reduce PM2.5 concentration and prevent frailty and chronic diseases.

Effects of cooking with solid fuel on hearing loss in Chinese adults-Based on two cohort studies.

The association between cooking fuel and hearing loss still needs more research to clarify, and two longitudinal cohort studies were explored to find if solid fuel use for cooking affected hearing in Chinese adults. The data from Chinese Health and Retirement Longitudinal Survey (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Participants (older than 18) without hearing loss at baseline and follow-up visits were included, which were divided into clean fuel and solid fuel groups. Hearing loss rate was from follow-up visits (both in year 2011) until the recent one (year 2018 in CHARLS and 2019 in CLHLS). Cox regressions were applied to examine the associations with adjustment for potential confounders. Fixed-effect meta-analysis was used to pool the results. A total of 9049 participants (average age 8.34 ± 9.12 [mean ± SD] years; 4247 [46.93%] males) were included in CHARLS cohort study and 2265 participants (average age, 78.75 ± 9.23 [mean ± SD] years; 1148 [49.32%] males) in CLHLS cohort study. There were 1518 (16.78%) participants in CHARLS cohort and 451 (19.91%) participants in CLHLS cohort who developed hearing loss. The group of using solid fuel for cooking had a higher risk of hearing loss (CHARLS: HR, 1.16; 95% CI 1.03-1.30; CLHLS: HR, 1.43; 95% CI 1.11-1.84) compared with the one of using clean fuel. Pooled hazard ratio showed the incidence of hearing loss in the solid fuel users was 1.17 (1.03, 1.29) times higher than that of clean fuel users. Hearing loss was associated with solid fuel use and older people were at higher risk. It is advised to replace solid fuel by clean fuel that may promote health equity.

Gestational exposure to PM2.5 disrupts fetal development by suppressing placental trophoblast syncytialization via progranulin/mTOR signaling.

Recent epidemiological and animal studies have indicated that ambient fine particulate matter (PM2.5) exposure during pregnancy is closely associated with intrauterine growth restriction (IUGR). However, the underlying mechanisms remain to be revealed. In this study, we found that gestational exposure to PM2.5 significantly decreased fetal weight and crown-rump length in mice, accompanied by insufficient placental trophoblast syncytialization and increased expression of progranulin (PGRN) in mice placenta. Administering PGRN neutralizing antibody to pregnant mice alleviated growth restriction and insufficient placental trophoblast syncytialization caused by PM2.5, accompanied with suppressed activation of the mTOR signaling pathway. Furthermore, in vitro experiments using human placental BeWo cells showed that 10 µg·mL-1 PM2.5 activated PGRN/mTOR signaling and suppressed forskolin-induced cell fusion, which was blocked by knockdown of PGRN. Taken together, our results demonstrated that PM2.5 exposure during pregnancy inhibited placental trophoblast syncytialization by activating PGRN/mTOR signaling, leading to abnormal placental development and IUGR. This study reveals a novel mechanism underlying the developmental toxicity of PM2.5 exposure during pregnancy.

The association between declining lung function and stroke risk: insights from an observational study and Mendelian randomization.

Background: Stroke, prevalent globally, particularly impacts low- and middle-income countries. Decreased lung function is one of the risk factors for stroke, and there is a lack of sufficient research on the association between the two, especially based on evidence from representative large samples. We aimed to explore the association between lung function and stroke incidence. Methods: We collected data from 13,371 participants from the 2007-2012 U.S. national cross-sectional study and 11,192 participants from the Chinese national cohort study during the 2011-2018 follow-up period. Multivariate logistic regression and Cox proportional hazards regression were used to assess cross-sectional and longitudinal associations of peak expiratory flow with stroke risks. Additionally, we used publicly available GWAS data from a European population to conduct Mendelian randomization analysis, further exploring the potential causal relationship. Results: The results of the cross-sectional study suggest that a decline in peak expiratory flow may be associated with an increased risk of stroke. The cohort study revealed that, compared to the first tertile group, the risk of stroke incidence in the second and third tertile groups of PEF decreased by 19% (hazard ratio (HR) = 0.810, 95%CI = 0.684-0.960) and 21.4% (HR = 0.786, 95%CI = 0.647-0.956), respectively. Mendelian randomization analysis clarified that higher PEF levels are significantly associated with a reduced risk of stroke (OR = 0.852, 95%CI = 0.727-0.997). Conclusion: Decreased lung function is a risk factor for stroke. As a simple and accurate indicator of lung function, PEF can be used to monitor lung function in community populations and patients for primary stroke prevention.

Lung function benefits of traditional Chinese medicine Qiju granules against fine particulate air pollution exposure: a randomized controlled trial.

Introduction: Multiple targets are considered as the causes of ambient fine particulate matter [aerodynamic diameters of < 2.5 µm (PM2.5)] induced lung function injury. Qiju granules are derived from the traditional Chinese medicine (TCM) formula known as Qi-Ju-Di-Huang-Wan (Lycium, Chrysanthemum, and Rehmannia Formula, QJDHW), which has been traditionally used to treat symptoms such as cough with phlegm, dry mouth and throat, and liver heat. This treatment approach involves attenuating inflammation, oxidative stress, and fibrosis response. This study investigated the effects of Qiju granules on protecting lung function against PM2.5 exposure in a clinical trial. Methods: A randomized, double-blinded, and placebo-controlled trial was performed among 47 healthy college students in Hangzhou, Zhejiang Province in China. The participants were randomly assigned to the Qiju granules group or the control group based on gender. Clinical follow-ups were conducted once every 2 weeks during a total of 4 weeks of intervention. Real-time monitoring of PM2.5 concentrations in the individually exposed participants was carried out. Data on individual characteristics, heart rate (HR), blood pressure (BP), and lung function at baseline and during the follow-ups were collected. The effects of PM2.5 exposure on lung function were assessed within each group using linear mixed-effect models. Results: In total, 40 eligible participants completed the scheduled follow-ups. The average PM2.5 level was found to be 64.72 µg/m3 during the study period. A significant negative correlation of lung function with PM2.5 exposure concentrations was observed, and a 1-week lag effect was observed. Forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal mid-expiratory flow (MMEF), forced expiratory flow at 75% of forced vital capacity (FVC) (FEF75), forced expiratory flow at 50% of FVC (FEF50), and forced expiratory flow at 25% of FVC (FEF25) were significantly decreased due to PM2.5 exposure in the control group. Small airway function was impaired more seriously than large airway function when PM2.5 exposure concentrations were increased. In the Qiju granules group, the associations between lung function and PM2.5 exposure were much weaker, and no statistical significance was observed. Conclusion: The results of the study showed that PM2.5 exposure was associated with reduced lung function. Qiju granules could potentially be effective in protecting lung functions from the adverse effects of PM2.5 exposure. Clinical Trial Registration: identifier: ChiCTR1900021235.