This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

ObjectiveTo investigate the effects of metformin on the immune functions of immature dendritic cells （imDCs） and the underlying mechanisms. MethodsMouse bone marrow-derived imDCs were treated with different concentrations of metformin. The working concentration and treatment time of metformin in this study were determined based on the results of cell apoptosis and cell viability assays. The effects of metformin on the phagocytic capacity of imDCs was evaluated using an antigen endocytosis assay. The expression of cluster of differentiation 205 （CD205）， the polymerization of filamentous actin （F-actin）， and the underlying regulatory mechanisms were investigated through flow cytometry， laser confocal fluorescence microscopy， and Western blot. ResultsThe working concentrations of metformin were 1， 2， 4 mmol/L for 24 h determined by the apoptosis and cell viability assays.Metformin significantly suppressed the phagocytic capacity of imDCs， down-regulated the expression of the mannose receptor CD205 on the cell surface， which was closely associated with phagocytic function； metformin inhibited the RhoA-ROCK1-LIMK1-Cofilin signaling pathway， which inhibited the polymerization of F-actin and disturbed its dynamic remodeling of imDCs. ConclusionMetformin can inhibit the expression of CD205 and disrupt the remodeling of F-actin， thereby suppressing the antigen-capturing capacity of imDCs.

Esculetin, a natural dihydroxy coumarin derived from the Chinese herbal medicine Cortex Fraxini, has demonstrated significant pharmacological activities, including anticancer properties. Ferroptosis, an iron-dependent form of regulated cell death, has garnered considerable attention due to its lethal effect on tumor cells. However, the exact role of ferroptosis in esculetin-mediated anti-hepatocellular carcinoma (HCC) effects remains poorly understood. This study investigated the impact of esculetin on HCC cells both in vitro and in vivo. The findings indicate that esculetin effectively inhibited the growth of HCC cells. Importantly, esculetin promoted the accumulation of intracellular Fe²⁺, leading to an increase in ROS production through the Fenton reaction. This event subsequently induced lipid peroxidation (LPO) and triggered ferroptosis within the HCC cells. The occurrence of ferroptosis was confirmed by the elevation of malondialdehyde (MDA) levels, the depletion of glutathione peroxidase (GSH-Px) activity, and the disruption of mitochondrial morphology. Notably, the inhibitor of ferroptosis, ferrostatin-1 (Fer-1), attenuated the anti-tumor effect of esculetin in HCC cells. Furthermore, the findings revealed that esculetin inhibited the Nrf2-xCT/GPx4 axis signaling in HCC cells. Overexpression of Nrf2 upregulated the expression of downstream SLC7A11 and GPX4, consequently alleviating esculetin-induced ferroptosis. In conclusion, this study suggests that esculetin exerts an anti-HCC effect by inhibiting the activity of the Nrf2-xCT/GPx4 axis, thereby triggering ferroptosis in HCC cells. These findings may contribute to the potential clinical use of esculetin as a candidate for HCC treatment.
Umbelliferones/administration & dosage* ; Ferroptosis/drug effects* ; Carcinoma, Hepatocellular/physiopathology* ; NF-E2-Related Factor 2/genetics* ; Humans ; Liver Neoplasms/physiopathology* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Animals ; Cell Line, Tumor ; Mice ; Amino Acid Transport System y+/genetics* ; Mice, Inbred BALB C ; Male ; Signal Transduction/drug effects* ; Lipid Peroxidation/drug effects* ; Reactive Oxygen Species/metabolism* ; Mice, Nude

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE. METHODS: In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction. RESULTS: The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185-0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252-0.980; P = 0.035), respectively. CONCLUSIONS Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.
Humans ; Pulmonary Embolism/complications* ; Case-Control Studies ; Male ; Ventricular Dysfunction, Right/physiopathology* ; Female ; Middle Aged ; Aged ; Coronary Stenosis/complications* ; Logistic Models ; Adult

Purpose: This study aimed to explore the potential categories of parenting sense of competence and to analyze the influence of rumination and dyadic coping on the potential categories of parenting sense of competence. Methods: A total of 199 postpartum women who met the criteria were surveyed from a tertiary grade-A hospital in Shanxi (China) from May 2023 to August 2023. The instruments included the general demographic characteristics, Chinese version of parenting sense of competence scale, Chinese event related rumination inventory, and Chinese version of dyadic coping inventory. Latent profile analysis (LPA) was used to classify the parenting sense of competence in postpartum women, and logistic regression analysis was used to identify the influencing factors. Results: The characteristics of parenting sense of competence in postpartum women can be divided into two potential categories, namely, easy-to-satisfy group (39.3%) and strict-demand group (60.7%). Logistic regression analysis showed that years of marriage, place of residence, deliberate rumination, and dyadic coping were the influencing factors of the potential categories of parenting sense of competence in postpartum women (p < .05). Conclusions Through Latent profile analysis (LPA) analysis, it was found that postpartum women's parenting sense of competence exhibits different characteristics. Clinical workers should identify the characteristics and influencing factors of different categories of women and adopt targeted intervention strategies to promote the level of parenting sense of competence.

Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Background:Currently,there are no effective biomarkers for predicting the progression of gastric precancerous lesions or screening early gastric cancer in clinical practice.Aims:To explore the expressions of adenylate cyclase 7(ADCY7),G protein-coupled receptor GPR86,glutamate receptor,ionotropic,N-methyl D-aspartate 2D(GRIN2D)and regulator of G protein signaling 4(RGS4)in various gastric mucosal lesions and their predictive value for progression of gastric precancerous lesions.Methods:Expressions of ADCY7,GPR86,GRIN2D,and RGS4 were detected by immuno-histochemistry,real-time PCR and Western blotting in Correa cascade(chronic non-atrophic gastritis,chronic atrophic gastritis,low-and high-grade intraepithelial neoplasia,and mucosal and submucosal early gastric cancer)and cancerous and para-cancerous tissues,among which,the differences in expression levels of these four factors were analyzed.Results:There was an increasing tendency in expression levels of ADCY7,GPR86,GRIN2D,and RGS4 from gastritis,intra-epithelial neoplasia to early gastric cancer.Except for GRIN2D expression between intraepithelial neoplasia and early gastric cancer,significant differences could be observed in any two groups(all P<0.001).Both mRNA and protein expression levels of GRP86 and GRIN2D were significantly higher in cancerous tissue than in adjacent tissue>5 cm(all P<0.05).Protein expression of RGS4 was significantly higher in cancerous tissue than in adjacent tissue>5 cm,but its mRNA expression presented an opposite trend(all P<0.05).Significant difference between cancerous tissue and adjacent tissue>5 cm in ADCY7 expression was only existed at protein level(P<0.05).Conclusions:Alterations of the expression levels of ADCY7,GPR86,GRIN2D,and RGS4 in Correa cascade and cancerous and para-cancerous tissues suggest that they are involved in the occurrence and development of gastric precancerous lesions,and might be used as predictors for progression of gastric precancerous lesions.

Purpose: This study aimed to explore the potential categories of parenting sense of competence and to analyze the influence of rumination and dyadic coping on the potential categories of parenting sense of competence. Methods: A total of 199 postpartum women who met the criteria were surveyed from a tertiary grade-A hospital in Shanxi (China) from May 2023 to August 2023. The instruments included the general demographic characteristics, Chinese version of parenting sense of competence scale, Chinese event related rumination inventory, and Chinese version of dyadic coping inventory. Latent profile analysis (LPA) was used to classify the parenting sense of competence in postpartum women, and logistic regression analysis was used to identify the influencing factors. Results: The characteristics of parenting sense of competence in postpartum women can be divided into two potential categories, namely, easy-to-satisfy group (39.3%) and strict-demand group (60.7%). Logistic regression analysis showed that years of marriage, place of residence, deliberate rumination, and dyadic coping were the influencing factors of the potential categories of parenting sense of competence in postpartum women (p < .05). Conclusions Through Latent profile analysis (LPA) analysis, it was found that postpartum women's parenting sense of competence exhibits different characteristics. Clinical workers should identify the characteristics and influencing factors of different categories of women and adopt targeted intervention strategies to promote the level of parenting sense of competence.

Objective To investigate the effect of Ba Bao Dan(BBD)on cardiac injury induced by doxorubicin in zebrafish.Methods We induced a zebrafish myocardial injury model using the chemotherapeutic drug,doxorubicin.We then examined the effects of different concentrations of BBD on pericardial edema and heart rate under an in vivo microscope.We also examined the inhibitory effects of BBD on neutrophil infiltration in the heart in Tg(mpx:EGFP)transgenic zebrafish.The impacts of BBD on superoxide dismutase,catalase,and malondialdehyde were observed.mRNA expression levels of ferroptosis-related factors,including glutathione peroxidase 4a(gpx4a),prostaglandin-endoperoxide synthase 2(ptgs2),arachidonate 5-lipoxygenase(alox5a),and acyl-CoA synthetase long-chain family member 4(acsl4)were determined by Real-time quantitative polymerase chain reaction.The accumulation of ferrous ions in zebrafish heart was assessed using a fluorescent probe for ferrous ions.Results BBD alleviated doxorubicin-induced pericardial edema and bradycardia in zebrafish,reduced neutrophil infiltration in the heart(P＜0.05),decreased malondialdehyde concentration(P＜0.05),and enhanced the activities of superoxide dismutase and catalase(P＜0.05).BBD also significantly inhibited ferroptosis,reduced the accumulation of ferrous ions in the zebrafish heart,suppressed the expression of ptgs2,alox5a,and acsl4(P＜0.05),and promoted the expression of gpx4a(P＜0.05).Conclusions BBD can attenuate doxorubicin-induced zebrafish myocardial injury and improve cardiac function by inhibiting lipid peroxidation and regulating ferroptosis.