OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases

Objective To explore the accumulated effects of physical activity,sedentary behavior,and sleep on cardiorespiratory fitness(CRF)among college students and provide effective measures for enhancing their CRF. Methods From May to June in 2023,223 college students aged 18 to 24 years old were recruited from Tianjin University of Science and Technology for a 24 hours activity behavior survey and CRF testing.Compositional analysis was employed to investigate the relationships of physical activity,sedentary behavior,and sleep with CRF.Isotemporal substitution models were established to predict the effects of substituting various activity behaviors on CRF.Results The proportion of time spent on moderate-to-vigorous physical activity(MVPA)was positively correlated with CRF of college students(β=6.40,P=0.002),while the proportion of time spent on sedentary behavior was negatively correlated with CRF(β=-3.02,P=0.004).Light physical activity(LPA)and sleep were not correlated with CRF(β=-1.06,P=0.504).Isotemporal substitution results for 15-min increments showed that replacing other activity behaviors with MVPA significantly increased the CRF of college students[SB:1.72 mL/(kg·min),95% CI=0.94-2.51;LPA:1.82 mL/(kg·min),95% CI=0.95-2.68;sleep:1.64 mL/(kg·min),95% CI=0.84-2.45].In the dose-response relationship from -30 min to 30 min,reallocating time from other behaviors to MVPA had greater adverse effect on CRF than reallocating time from MVPA to other behaviors.Among all the substitutions,replacing LPA with MVPA had the most beneficial effect on improving CRF.Additionally,a 5-min increment was considered the optimal tipping point for MVPA replacing other activities.Conclusions This study underscores the importance of participating in MVPA for improving the CRF of college students.The isotemporal substitution model provides clear goals for the allocation of time for these behaviors,aiding in future intervention measure development and policy-making.
Humans ; Sedentary Behavior ; Sleep ; Students ; Cardiorespiratory Fitness ; Exercise ; Young Adult ; Adolescent ; Universities ; Male ; Female

Objective:To analyze the prevalence trends and epidemiological characteristics of cardiometabolic multimorbidity(CMM) in Beijing from 2005 to 2022.Methods:A series of representative cross-sectional surveys were conducted in Beijing between 2005 and 2022 using a stratified multistage cluster random sampling method. A total of 110 496 permanent residents aged 18-79 years participated in face-to-face interviews, physical examinations, and laboratory testing. Complex sampling logistic regression models were employed to identify factors associated with CMM, and Joinpoint regression was used to assess temporal trends in prevalence. Results:The prevalence of CMM was 22.3% in 2005 and 24.3% in 2022, with an average annual percent change of 0.1%(95% CI -1.3%-1.3%, P>0.05). In rural areas, the prevalence increased by 1.3% per year(95% CI 0.2%-2.6%, P<0.05), while among obese individuals, it decreased by 1.0% annually( P<0.05). The most common CMM patterns were hypertension combined with dyslipidemia(13.2%), hypertension combined with diabetes(7.0%), and diabetes combined with dyslipidemia(5.8%). The prevalence of hypertension and dyslipidemia comorbidity showed a long-term decline among females, those aged 60-79 and obese individuals( P<0.05). In contrast, the prevalence of hypertension and diabetes comorbidity increased over time in rural residents and individuals with normal body weight( P<0.05). Furthermore, diabetes and dyslipidemia comorbidity rates increased significantly among males, adults aged 18-59 years, those with a college education or above, rural residents and individuals with normal body weight( P<0.05). Multivariable logistic regression indicated that male, older age, overweight, obese, and lower education level were independently associated with a higher risk of CMM( P<0.05). Conclusion:From 2005 to 2022, the prevalence of CMM remained high among adults in Beijing. While prevalence decreased among obese individuals, it increased significantly in rural areas. Hypertension combined with dyslipidemia was the most common multimorbidity pattern throughout the study period.

Alzheimer's disease(AD), a neurodegenerative disorder associated with aging, is the most prevalent form of dementia.As the aging population continues to expand, AD presents significant health and caregiving challenges for families and society, making it a pressing international public health concern.In recent years, numerous countries have implemented dementia prevention and treatment strategies that emphasize community-based comprehensive approaches.Currently, the community-based AD prevention and treatment model in China is still in the exploratory phase, with community efforts lacking organization.In alignment with China's action plan for advancing dementia prevention and treatment, and to achieve the strategic objective of "healthy aging, " this consensus is based on the principle of three-level prevention and is tailored to the characteristics of AD disease progression.It aims to develop a comprehensive prevention and treatment strategy for AD that is suitable for communities in China, providing technical guidance and support to establish a scientific basis for formulating community AD prevention and treatment models.

Objective:To investigate the effect of abdominal circumference on intestinal radiation dose volume and acute intestinal toxicity in pelvic intensity modulated radiation therapy for rectal cancer.Methods:A total of 150 patients with locally advanced rectal cancer (LARC) who received adjuvant and neoadjuvant concurrent chemoradiotherapy at the Affiliated Cancer Hospital of Guizhou Medical University from March 2023 to January 2025 were enrolled, including 82 cases of adjuvant radiotherapy and 68 cases of neoadjuvant radiotherapy. All patients underwent radiotherapy CT simulation positioning in the standard mode of prone position with abdominal board padding and bladder filling. Intestinal toxicity was categorized as a binary variable based on the occurrence of ≥2 grade acute intestinal toxicity. Linear and logistic regression models were used to analyze the factors influencing intestinal radiation dose volumes (V 10, V 20, V 30, V 40) and acute intestinal toxicity in LARC patients. Generalized additive models and piecewise linear and logistic regression analyses were employed to examine the threshold effects of abdominal circumference on intestinal radiation dose volumes and acute intestinal toxicity. The threshold value for abdominal circumference was determined based on the upper limit of the 95% CI for the threshold. A difference test was used to validate the differences in intestinal radiation dose volume and acute intestinal toxicity between small and medium-to-large abdominal circumferences. Results:Univariate analysis showed that, gender, body mass, abdominal circumference, planning target volume (PTV), intestinal volume were all influencing factors for the radiation dose volumes (V 10, V 20, V 30, V 40) of each intestinal segment of patients with LARC undergoing adjuvant radiotherapy (all P<0.05). Body mass, abdominal circumference, intestinal volume were all influencing factors for the radiation dose volumes (V 10, V 20, V 30, V 40) of each intestinal segment of patients with LARC undergoing neoadjuvant radiotherapy (all P<0.05). Body mass index (BMI), abdominal circumference, intestinal volume and individual intestinal radiation volumes (V 10, V 20, V 30, V 40) were all influencing factors for the acute intestinal toxicity of patients with LARC undergoing adjuvant radiotherapy (all P<0.05). Body mass, BMI, abdominal circumference, multiple intestinal radiation dose volumes (V 20, V 30, V 40) were all influencing factors for the acute intestinal toxicity of patients with LARC undergoing neoadjuvant radiotherapy (all P<0.05). Multivariate analysis showed that, abdominal circumference (V 10: β=-1.01, 95% CI: -1.68--0.33, P=0.004; V 20: β=-0.94, 95% CI: -1.28--0.60, P<0.001; V 30: β=-0.58, 95% CI: -0.82--0.34, P<0.001; V 40: β=-0.41, 95% CI: -0.60--0.23, P<0.001) was an independent influencing factor for the radiation dose volume of each intestinal segment of patients with LARC undergoing adjuvant radiotherapy. Abdominal circumference (V 10: β=-0.92, 95% CI: -1.62--0.22, P=0.010; V 20: β=-0.84, 95% CI: -1.11--0.57, P<0.001; V 30: β=-0.42, 95% CI: -0.57--0.28, P<0.001; V 40: β=-0.30, 95% CI: -0.41--0.19, P<0.001) was an independent influencing factor for the radiation dose volume of each intestinal segment of patients with LARC undergoing neoadjuvant radiotherapy. Abdominal circumference ( OR=0.86, 95% CI: 0.78-0.95, P=0.002) was an independent influencing factor for the acute intestinal toxicity of patients with LARC undergoing adjuvant radiotherapy. Abdominal circumference ( OR=0.87, 95% CI: 0.79-0.96, P=0.004) was an independent influencing factor for the acute intestinal toxicity of patients with LARC undergoing neoadjuvant radiotherapy. The generalized additive model revealed a nonlinear relationship between abdominal circumference and intestinal radiation dose volume and acute intestinal toxicity of adjuvant radiotherapy patients. Further segmented regression analysis results showed that there was a threshold effect between abdominal circumference and intestinal radiation dose volume (V 10, V 20, V 30, V 40) and acute intestinal toxicity. The inflection point values between abdominal circumference and intestinal radiation dose volume V 10, V 20, V 30, V 40 in LARC patients undergoing adjuvant radiotherapy were all 71.9 cm; the inflection point values between abdominal circumference and the intestinal radiation dose volume V 10, V 20, V 30, V 40 in LARC patients undergoing neoadjuvant radiotherapy were 69.0, 69.0, 69.0, 68.6 cm, respectively; The inflection point values between abdominal circumference and acute intestinal toxicity in LARC patients undergoing adjuvant radiotherapy and neoadjuvant radiotherapy were 71.9, 69.0 cm, respectively. Based on the upper limit of the 95% CI threshold, the cutoff values for small and medium-to-large abdominal circumferences for patients undergoing adjuvant and neoadjuvant radiotherapy were set at 76.1, 71.9 cm, respectively. In patients undergoing adjuvant radiotherapy, the levels of intestinal radiation dose volume V 10 [ (7.65±2.29) cm 3vs. (5.88±2.68) cm 3, t=2.76, P=0.007], V 20 [ (4.28±1.27) cm 3vs. (2.72±1.31) cm 3, t=4.81, P<0.001], V 30 [ (2.42±1.07) cm 3vs. (1.37±0.76) cm 3, t=4.95, P<0.001], V 40 [ (1.69±0.74) cm 3vs. (0.92±0.58) cm 3, t=4.93, P<0.001] in the small abdominal circumference group ( n=22) were significantly higher than those in patients with medium-to-large abdominal circumferences ( n=60) ; In patients undergoing neoadjuvant radiotherapy, patients with small abdominal circumferences ( n=11) had significantly higher V 20 [ (3.09±0.84) cm 3vs. (2.28±1.17) cm 3, t=2.17, P=0.033], V 30 [1.44 (1.22, 1.53) cm 3vs. 0.91 (0.56, 1.22) cm 3, Z=-3.04, P=0.002], V 40 [0.93 (0.84, 1.09) cm 3vs. 0.44 (0.30, 0.81) cm 3, Z=-3.19, P=0.001] than patients with medium-to-large abdominal circumferences ( n=57). In patients receiving adjuvant radiotherapy and neoadjuvant radiotherapy, there were statistically significant differences in acute intestinal toxicity between patients with small abdominal circumferences and with medium-to-large abdominal circumferences ( χ2=10.46, P=0.001; χ2=8.13, P=0.004) . Conclusions:In the standard mode (prone position with abdominal board padding and bladder filling), abdominal circumference is an independent factor influencing the intestinal radiation dose volume and acute intestinal toxicity in rectal cancer radiotherapy patients. There is a significant non-linear threshold effect between abdominal circumference and different levels of intestinal radiation dose volume and acute intestinal toxicity. The impact of abdominal circumference on intestinal radiation dose volume and toxicity differs significantly before and after the inflection point value. Patients with smaller abdominal circumferences not only fail to achieve the expected benefits under the current standard radiotherapy regimen but also face higher risks of intestinal radiation dose volume and toxicity.

Objective To explore the bioactive components in Jiawei Xiaoyao Pills(JWXYP)and their mechanisms for alleviating depression-like behaviors.Methods The active compounds,key targets,and pathways of JWXYP were identified using TCMSP and TCMIP databases.Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress(CUMS)-induced depression groups.After modeling,the 5 model groups were treated with daily gavage of normal saline,1.8 mg/kg fluoxetine hydrochloride(positive control drug),or JWXYP at 1.44,2.88,and 4.32 g/kg.The depression-like behaviors of the rats were evaluated using behavioral tests,and pathological changes in the liver and hippocampus were examined with HE staining.The biochemical indicators in the serum and brain tissues were detected using ELISA.Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA,and gut microbiota changes were analyzed using 16S rDNA sequencing.Results Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system.In the rat models subjected to CUMS,treatment with JWXYP significantly improved body weight loss,sucrose preference and open field activities,reduced liver inflammation,alleviated structural changes in the hippocampal neurons,decreased serum levels of TNF-α,IL-1β,IL-6 and LBP,and increased 5-HT and VIP concentrations in the serum and brain tissue,and these effects were the most pronounced in the high-dose group.Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats,involving the pathways for bile acid biosynthesis and amino acid metabolism.16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats.Conclusion JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters,inhibiting inflammation and oxidation,and modulating gut microbiota.

OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*

Objective:To investigate the clinical characteristics and cardiac magnetic resonance (CMR) features of cardiac sarcoidosis (CS).Methods:This retrospective study included 8 consecutive patients with pathologically confirmed CS by endomyocardial biopsy from Fuwai Hospital, Chinese Academy of Medical Sciences, between January 2012 and September 2024. All patients underwent comprehensive CMR examinations including cine imaging and late gadolinium enhancement (LGE) imaging. Clinical data, including electrocardiographic findings, were collected. CMR phenotyping was performed based on imaging characteristics, and cardiac structure and function parameters were evaluated. LGE analysis was conducted using the American Heart Association 17-segment model to assess the distribution patterns and involvement sites.Results:The most common clinical symptoms were chest tightness (4 patients), palpitations (4 patients), and shortness of breath (6 patients). Electrocardiographic abnormalities included atrioventricular block in 4 patients, right bundle branch block in 2 patients, left bundle branch block in 2 patients, frequent premature ventricular contractions in 4 patients, and non-sustained ventricular tachycardia in 5 patients. CMR phenotyping revealed hypertrophic cardiomyopathy pattern in 3 patients, with 2 patients maintaining normal biventricular function and 1 patient showing significantly reduced biventricular systolic function. Dilated cardiomyopathy pattern was identified in 4 patients, all demonstrating significantly impaired biventricular systolic function. One patient exhibited another phenotype with preserved biventricular systolic function. LGE analysis demonstrated that the anterior wall and anterior septum (segments 1, 2, 7, 8) were the most frequently involved regions, followed by the lateral and inferior walls (segments 5, 6, 11, 12). Subepicardial involvement was the predominant pattern of myocardial enhancement.Conclusions:Cardiac sarcoidosis exhibits diverse clinical manifestations and heterogeneous imaging characteristics. CMR not only provides a comprehensive assessment of cardiac structure and function but also reveals distinctive myocardial tissue characteristics, particularly the extent and distribution patterns of LGE involvement. These findings have significant reference value for early identification of CS and differential diagnosis from other cardiomyopathies.

Dark plum can be used to treat symptoms such as consumptive thirst due to deficiency-heat and chronic cough due to lung deficiency.Its active ingredients have auxiliary effects on lowering blood glucose,antibacterial and anti-inflammatory activities.Insulin resistance is mainly characterized by the weakening of the physiological effects of insulin in the body,with a relatively complex mechanism that can lead to various metabolic-related diseases and seriously affect health.The active ingredients of dark plum can improve insulin resistance by regulating insulin signaling pathways,endoplasmic reticulum stress,antioxidant stress,inflammatory signaling pathways,levels of related inflammatory mediators,and free fatty acid levels.By reviewing the relevant literature on the improvement of insulin resistance by the active ingredients of dark plum,this article summarizes and analyzes its mechanism of action,aiming to provide new ideas and scientific evidence for in-depth research on insulin resistance and the development and application of drugs.

This study aimed to investigate the effect of saltwater stir-fried Plantaginis Semen(SPS) on renal fibrosis in rats and decipher the underlying mechanism. Thirty-six Sprague-Dawley rats were randomly assigned into control, model, losartan potassium, and low-, medium-, and high-dose(15, 30, and 60 g·kg~(-1), respectively) SPS groups. Rats in other groups except the control group were subjected to unilateral ureteral obstruction(UUO) to induce renal fibrosis, and the modeling and gavage lasted for 14 days. After 14 consecutive days of treatment, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in rats of each group were determined by an automatic biochemical analyzer. Hematoxylin-eosin(HE) and Masson staining were used to evaluate pathological changes in the renal tissue. Western blot and immunofluorescence assay were conducted to determine the protein levels of fibronectin(FN), collagen Ⅰ, vimentin, and α-smooth muscle actin(α-SMA) in the renal tissue. The mRNA levels of epithelial-mesenchymal transition(EMT)-associated transcription factors including twist family bHLH transcription factor 1(TWIST1), snail family transcriptional repressor 1(SNAI1), and zinc finger E-box binding homeobox 1(ZEB1), as well as inflammatory cytokines such as interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), were determined by RT-qPCR. Human renal proximal tubular epithelial(HK2) cells exposed to transforming growth factor-β(TGF-β) for the modeling of renal fibrosis were used to investigate the inhibitory effect of SPS on EMT. Network pharmacology and Western blot were employed to explore the molecular mechanism of SPS in alleviating renal fibrosis. The results showed that SPS significantly reduced Scr and BUN levels and alleviated renal injury and collagen deposition in UUO rats. Moreover, SPS notably down-regulated the protein levels of FN, collagen Ⅰ, vimentin, and α-SMA as well as the mRNA levels of SNAI1, ZEB1, TWIST1, IL-1β, IL-6, and TNF-α in the kidneys of UUO rats and TGF-β-treated HK-2 cells. In addition, compared with Plantaginis Semen without stir-frying with saltwater, SPS showed increased content of specific compounds, which were mainly enriched in the mitogen-activated protein kinase(MAPK) signaling pathway. SPS significantly inhibited the phosphorylation of extracellular signal-regulated kinase(ERK) and p38 MAPK in the kidneys of UUO rats and TGF-β-treated HK2 cells. In conclusion, SPS can alleviate renal fibrosis by attenuating EMT through inhibition of the MAPK signaling pathway.
Animals ; Epithelial-Mesenchymal Transition/drug effects* ; Rats, Sprague-Dawley ; Male ; Rats ; Fibrosis/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Kidney Diseases/pathology* ; Kidney Tubules/pathology* ; Humans