ObjectiveTo investigate the protective effect and mechanism of Wendan Ningxin granules （WNG） on susceptibility to atrial fibrillation （AF） in mice with inflammatory injury. Methods100 C57BL/6 mice were divided into a blank control group， a model group， a low-dose WNG group （2.34 g·kg^-1·d^-1）， a high-dose WNG group （4.68 g·kg^-1·d^-1）， and an amiodarone positive control group （0.091 g·kg^-1·d^-1）， with 20 mice in each group. Except for the blank control group， mice in other groups received intraperitoneal injections of lipopolysaccharide （LPS） to establish an inflammatory injury model. Treatment groups received continuous intragastric administration of their respective interventions for four weeks. During the fourth week， the treatment groups received LPS injections concurrently with their treatments. The blank control and model groups received distilled water （10 mL·kg^-1·d^-1） by gavage， with a gavage volume of 10 mL·kg^-1 for all groups， once daily. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe atrial tissue morphology and fibrosis degree. Immunohistochemistry was used to assess the expression of α-smooth muscle actin （α-SMA） in mouse atrial tissue. Electrophysiological detection was performed using a multi-channel electrophysiology mapping system to measure AF inducibility， AF duration， and atrial effective refractory period （AERP）. High-resolution optical mapping was used to measure action potential duration （APD） dispersion， conduction heterogeneity index， and calcium transient （CaT） dispersion. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of proteins related to diastolic calcium leakage in mouse atria： Ca²⁺/calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）， ryanodine receptor 2（RyR2）， sarco/endoplasmic reticulum Ca²⁺-ATPase （SERCA）， and sodium-calcium exchanger （NCX）. Western blot analysis was performed to detect the expression of CaMKII， RyR2， SERCA， and NCX proteins in myocardial tissue from each group. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of inflammatory factors interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）. ResultsPathological staining results showed that compared with the blank control group， the model group exhibited disrupted atrial tissue structure， inflammatory cell infiltration， atrial fibrosis， and diffuse infiltration of numerous brown α-SMA positive cells in the atrial interstitium （P<0.01）. AF could be induced by electrical stimulation with a longer duration. AERP was shortened， while APD dispersion， conduction heterogeneity index， and CaT dispersion were increased （P<0.01）. The expression of proteins associated with diastolic calcium leakage， including CaMKⅡ， RyR2， and NCX1， showed elevated mRNA and protein levels， whereas SERCA2a mRNA and protein expression decreased （P<0.05）. Serum levels of inflammatory factors IL-1β and TNF-α were elevated （P<0.01）. Compared with the model group， intervention with WNG alleviated cardiac structural damage， reduced inflammatory cell infiltration， improved atrial fibrosis， and reduced the diffuse infiltration of α-SMA positive cells （P<0.01）. AF inducibility and AF duration upon electrical stimulation were significantly reduced （P<0.05）， AERP was prolonged （P<0.05）， mRNA and protein expression of CaMKⅡ， RyR2， and NCX1-proteins associated with diastolic calcium leakage-were reduced， whilst mRNA and protein expression of SERCA2a increased （P<0.05）， and serum levels of IL-1β and TNF-α were decreased （P<0.01）. ConclusionBoth low‑ and high‑dose WNG can effectively reduce susceptibility to inflammation-related AF. The mechanism by which WNG reduce AF susceptibility may be related to regulating proteins involved in sarcoplasmic reticulum diastolic calcium leak， thereby improving cardiac electrical remodeling， and alleviating inflammation-induced myocardial fibrosis， thus improving cardiac structural remodeling.

Background: Optimizing cultivation techniques for traditional Chinese medicine has become a crucial means to improve the quality of medicinal materials. Microbial agents, as environmentally friendly and efficient plant growth promoters and soil conditioners, have increasingly attracted attention in eco-agriculture research. Objective: Our understanding remains limited regarding how the application of microbial agents, alone or in combination, affects changes in the rhizosphere microbiome and its association with the bioactive components of medicinal materials. Methods: In this study, Epimedium pubescens Maxim. was employed as a model plant to examine the effects of 2 microbial agents(Paenibacillus mucilaginosus and Bacillus subtilis) applied individually and in combination on plant growth and the accumulation of bioactive components. Additionally, this study explored the relationship between the rhizosphere microbiome and plant development. Results: The application of microbial agents increased the yield of E. pubescens leaves by 20.30% to 33.66% and enhanced the total flavonol glycosides content by 11.40% to 29.94%. Meanwhile, microbial treatments reshaped the rhizosphere microbiome, promoted the enrichment of beneficial microorganisms (e.g., Frankia and Paenibacillus), suppressed phytopathogenic fungi such as Didymella and Scytalidium, and enhanced the stability of the soil microbial co-occurrence network. The partial least squares path model suggested that microbial agents not only directly impact the quality of medicinal herbs but also indirectly alter the accumulation of bioactive components by modulating the soil microbiome. Conclusion: These findings deepen our understanding of the relationship between medicinal plant quality and rhizosphere microbiomes as mediated by microbial agents. They also provide a basis for designing and manipulating synthetic microbial communities to promote sustainable development in eco-agriculture.

Objective:To evaluate the levels and source of cadmium exposure by dietary pathway among middle-aged and elderly people ≥40 in cadmium-contaminated areas of China.Methods:A total of 7 193 people aged 40-89 years from four typical cadmium-contaminated areas in China were selected as the study subjects. Food Frequency Questionnaire (FFQ), Total Diet Study (TDS) and a 3-day-24-hour dietary recall survey were conducted. Dietary cadmium intake and food sources through dietary pathways were assessed based on cadmium content in foods, consumption amounts and intake frequencies.Results:The mean age of the participants was 63.39±12.21 years, with 50.05% being males. The average monthly dietary cadmium intake was 7.39 μg/(kg·BW). Staple foods and vegetables were the primary sources of dietary cadmium intake, accounting for 57.51% and 32.48%, respectively. The monthly dietary cadmium intake in all surveyed regions did not exceed the Provisional Tolerable Monthly Intake (PTMI) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).Conclusion:The monthly dietary cadmium intake among middle-aged and elderly people in cadmium-contaminated areas of China is relatively low, with the risk remaining at an acceptable level. Staple foods and vegetables are the most significant contributors to dietary cadmium intake.

Background:Optimizing cultivation techniques for traditional Chinese medicine has become a crucial means to improve the quality of medicinal materials.Microbial agents,as environmentally friendly and efficient plant growth promoters and soil conditioners,have increasingly attracted attention in eco-agriculture research.Objective:Our understanding remains limited regarding how the application of microbial agents,alone or in combination,affects changes in the rhizosphere microbiome and its association with the bioactive components of medicinal materials.Methods:In this study,Epimedium pubescens Maxim.was employed as a model plant to examine the effects of 2 microbial agents(Paenibacillus mucilaginosus and Bacillus subtilis)applied individually and in combination on plant growth and the accumulation of bioactive components.Additionally,this study explored the relationship between the rhizosphere microbiome and plant development.Results:The application of microbial agents increased the yield of E.pubescens leaves by 20.30％to 33.66％and enhanced the total flavonol glycosides content by 11.40％to 29.94％.Meanwhile,microbial treatments reshaped the rhizosphere microbiome,promoted the enrichment of beneficial microorganisms(e.g.,Frankia and Paenibacillus),suppressed phytopathogenic fungi such as Didymella and Scytalidium,and enhanced the stability of the soil microbial co-occurrence network.The partial least squares path model suggested that microbial agents not only directly impact the quality of medicinal herbs but also indirectly alter the accumula-tion of bioactive components by modulating the soil microbiome.Conclusion:These findings deepen our understanding of the relationship between medicinal plant quality and rhizosphere micro-biomes as mediated by microbial agents.They also provide a basis for designing and manipulating synthetic microbial communities to promote sustainable development in eco-agriculture.

Objective:To evaluate the levels and source of cadmium exposure by dietary pathway among middle-aged and elderly people ≥40 in cadmium-contaminated areas of China.Methods:A total of 7 193 people aged 40-89 years from four typical cadmium-contaminated areas in China were selected as the study subjects. Food Frequency Questionnaire (FFQ), Total Diet Study (TDS) and a 3-day-24-hour dietary recall survey were conducted. Dietary cadmium intake and food sources through dietary pathways were assessed based on cadmium content in foods, consumption amounts and intake frequencies.Results:The mean age of the participants was 63.39±12.21 years, with 50.05% being males. The average monthly dietary cadmium intake was 7.39 μg/(kg·BW). Staple foods and vegetables were the primary sources of dietary cadmium intake, accounting for 57.51% and 32.48%, respectively. The monthly dietary cadmium intake in all surveyed regions did not exceed the Provisional Tolerable Monthly Intake (PTMI) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).Conclusion:The monthly dietary cadmium intake among middle-aged and elderly people in cadmium-contaminated areas of China is relatively low, with the risk remaining at an acceptable level. Staple foods and vegetables are the most significant contributors to dietary cadmium intake.

Background:Optimizing cultivation techniques for traditional Chinese medicine has become a crucial means to improve the quality of medicinal materials.Microbial agents,as environmentally friendly and efficient plant growth promoters and soil conditioners,have increasingly attracted attention in eco-agriculture research.Objective:Our understanding remains limited regarding how the application of microbial agents,alone or in combination,affects changes in the rhizosphere microbiome and its association with the bioactive components of medicinal materials.Methods:In this study,Epimedium pubescens Maxim.was employed as a model plant to examine the effects of 2 microbial agents(Paenibacillus mucilaginosus and Bacillus subtilis)applied individually and in combination on plant growth and the accumulation of bioactive components.Additionally,this study explored the relationship between the rhizosphere microbiome and plant development.Results:The application of microbial agents increased the yield of E.pubescens leaves by 20.30％to 33.66％and enhanced the total flavonol glycosides content by 11.40％to 29.94％.Meanwhile,microbial treatments reshaped the rhizosphere microbiome,promoted the enrichment of beneficial microorganisms(e.g.,Frankia and Paenibacillus),suppressed phytopathogenic fungi such as Didymella and Scytalidium,and enhanced the stability of the soil microbial co-occurrence network.The partial least squares path model suggested that microbial agents not only directly impact the quality of medicinal herbs but also indirectly alter the accumula-tion of bioactive components by modulating the soil microbiome.Conclusion:These findings deepen our understanding of the relationship between medicinal plant quality and rhizosphere micro-biomes as mediated by microbial agents.They also provide a basis for designing and manipulating synthetic microbial communities to promote sustainable development in eco-agriculture.

Objective:To investigate the preventive and therapeutic effects of compound wild chrysanthemum eye pad on blue light-induced alteration of meibomian gland function in mice and its mechanism.Methods:Sixty-four 15-week-old male C57BL/6J mice were divided into two groups of 32 mice each according to random numbers for the prevention test and the treatment test.The respective 32 mice in the prevention and treatment experiments were randomly divided into normal group, blue light group, solvent group and eye pad group according to random numbers, with eight mice in each group, respectively.In the prevention experiments, mice in each group were exposed to blue light at a wavelength of 460 nm and a light intensity of 2 000 lx for 6 hours per day for 15 consecutive days to establish a mouse model of meibomian gland function changes except for the normal group.The solvent group and the eye pad group were treated with the corresponding eye pad before and after the blue light exposure for 25 minutes daily for the 15 consecutive days.The blue light group was treated with blue light exposure only for 15 days, and the mice were photographed at the edge of the meibomian gland on day 15 to observe the function of the meibomian gland except for the normal group.In the treatment test, all groups of mice except the normal group were induced the altered function of the mouse meibomian gland by the above method.The solvent and eye pad groups were treated with corresponding eye pads for 25 minutes in the morning and afternoon of each day for 15 consecutive days after blue light exposure.The blue light group was kept in a standard environment for 15 days and the changes in meibomian gland function of mice were detected by meibomian gland photographs on day 15.Photography of the eyelid margin in vitro, oil red O staining, and hematoxylin-eosin staining were performed to observe the histologic changes in the meibomian glands of mice after the preventive and experimental treatment.The relative expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) mRNA in mouse meibomian gland tissues was detected by real-time fluorescence quantitative PCR.The expression of nuclear factor-κB (NF-κB) and phosphorylation of NF-κB (p-NF-κB) proteins in mice meibomian gland tissues was detected by Western blot to assess the degree of amelioration of blue light-induced inflammation in mouse meibomian glands by the compound wild chrysanthemum eye pad.This study was conducted in accordance with the Statement of the Association for Research in Vision and Ophthalmology on the Use of Animals in Ophthalmology and Vision Research, and was approved by the Animal Ethics Committee of Xiamen University (No.XMULAC20220258). Results:Compared with the normal group, a gradually increased number of blocked meibomian gland openings, and a gradually decreased remaining area of lower meibomian gland, were observed in the mice after 15 days of blue light group, and all the differences were statistically different (all at P<0.05). In the prevention test, the number of obstructed opening in the eye pad group was 1.833±0.753, which was significantly less than 3.667±1.033 in the solvent group ( P<0.05). The relative remaining area of the lower lid meibomian gland in the eye pad group was 0.718±0.091, which was significantly greater than 0.624±0.130 in the solvent group ( P<0.05). Hematoxylin-eosin staining showed inflammatory cell infiltration in mouse meibomian gland in the blue light and solvent groups.There was no inflammatory cell infiltration in eye pad group, and the morphology of the acini was similar to that of the normal group.Oil red O staining showed that there was no significant lipid deposition in the groups.The relative expressions of IL-1β, IL-6, TNF-α, and IFN-γ mRNA were significantly lower, and the relative expressions of NF-κB and p-NF-κB proteins were significantly lower in the eye pad group than in the solvent group, showing statistically significant differences (all at P<0.05). In the treatment test, the number of obstructed openings in the eye pad group and solvent group was 4.333±1.211 and 4.833±1.722, respectively, and the relative remaining area of the lower meibomian gland was 0.572±0.151 and 0.588±0.154, respectively, showing no statistically significant differences (both at P>0.05). Hematoxylin-eosin staining showed inflammatory cell infiltration in mouse meibomian glands in the blue light and solvent groups, with a similar morphology of acini as in the normal group.There was no inflammatory cell infiltration in eye pad group.Oil red O staining showed that there was no significant lipid deposition in the groups.The relative expressions of IL-1β, IL-6, and IFN-γ mRNA were significantly lower and the relative expressions of NF-κB and p-NF-κB proteins were significantly lower in the eye pad group than in the solvent group (all at P<0.05). Conclusions:Compound wild chrysanthemum eye pad may have preventive and therapeutic effects on blue light-induced changes in meibomian gland function by reducing the inflammatory response of meibomian gland tissue through the inhibition of the NF-κB signaling pathway.

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.