ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 （STAT1）/interferon regulatory factor 3 （IRF3） signaling pathway in a pneumonia model induced by lipopolysaccharide （LPS） and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group， and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling， the rats were randomly divided into the model group， dexamethasone group （0.5 mg·kg^-1）， and Yifei Jianpi prescription high-dose （12 mg·kg^-1）， medium-dose （6 mg·kg^-1）， and low-dose （3 mg·kg^-1） groups， with 10 rats in each group. Treatment was administered once daily， and the normal control and model groups received the same volume of normal saline. After 14 days， flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of immunoglobulin G （IgG）， immunoglobulin A （IgA）， immunoglobulin M （IgM）， and the content of tumor necrosis factor-α （TNF-α）， interleukin-8 （IL-8）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in alveolar lavage fluid （BALF）. Hematoxylin-eosin （HE） staining was used to observe lung tissue pathology and score the damage. Thymus weight， spleen weight， and wet-to-dry weight ratio （W/D） were recorded. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of STAT1， IRF3， IL-6， and interferon-alpha （IFN-α） in lung tissues， while Western blot was performed to assess the protein expression of STAT1， IRF3， IL-6， and IFN-α. ResultsCompared with the normal control group， the model group showed significantly increased proportion of B lymphocytes in peripheral blood， decreased proportions of NK cells and CD4⁺/CD8⁺ （P<0.05， P<0.01）， decreased serum levels of IgG and IgA， significantly increased IgM levels （P<0.01）， significantly elevated content of TNF-α， IL-6， and IL-8 in BALF， and significantly decreased IL-10 levels （P<0.01）. Lung tissue damage was evident， with significant increases in thymus and spleen weights and a higher W/D ratio （P<0.01）. The mRNA and protein expression of STAT1， IRF3， IFN-α， and IL-6 in lung tissues was significantly upregulated （P<0.05，P<0.01）. Compared with the model group， the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood， increased proportions of NK cells and CD4⁺/CD8⁺ ratios （P<0.05， P<0.01）， significantly increased serum levels of IgG and IgA， significantly decreased IgM levels （P<0.05， P<0.01）， significantly reduced levels of TNF-α， IL-6， and IL-8 in BALF， and significantly increased IL-10 levels （P<0.01）. Lung tissue damage was alleviated， thymus and spleen weights were significantly reduced， and the W/D ratio was markedly decreased （P<0.01）. The mRNA and protein expression of STAT1， IRF3， IFN-α， and IL-6 in lung tissues was significantly downregulated （P<0.05， P<0.01）. ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.

Objective To investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

OBJECTIVE To explore the effects and potential mechanism of plumbagin on the inflammatory response and oxidative stress in rats with acute exacerbation of chronic obstructive pulmonary disease （AECOPD） based on Notch1/GATA3 signaling pathway. METHODS Ten rats were randomly selected as the control group； another 65 rats were used to establish the AECOPD model by inhaling cigarette smoke， intratracheal administration of endotoxin， and nasal inoculation of bacteria. The 50 successfully modeled rats were randomly divided into the AECOPD group， plumbagin low-dose group （10 mg/kg）， plumbagin high-dose group （50 mg/kg）， positive control group （dexamethasone 0.09 mg/kg）， and high-dose plumbagin+Jagged1 （Notch1 activator） group （50 mg/kg+25 mg/kg）， with 10 rats in each group. Each group was administrated intragastrically or intraperitoneally with the corresponding drug solution or normal saline， once a day for 28 consecutive days. After the last administration， the lung function indicators （peak expiratory flow， the ratio of forced expiratory volume in 0.3 seconds to forced vital capacity）， the number of inflammatory cells （white blood cells， lymphocytes， neutrophils， macrophages） in bronchoalveolar lavage fluid， the levels of inflammatory factors [interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α （TNF-α）] in lung tissue， and the contents of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in lung tissue were all determined in each group； the pathological changes of lung tissue and the pathological scores， as well as protein expressions of mucin 5ac （Muc5ac）， Notch1 and GATA3 in lung tissue were also detected. RESULTS Compared with the control group， the lung tissue of the AECOPD group rats showed severe damage to the alveolar wall structure， with a large number of inflammatory cells infiltration and accompanied by pathological changes such as thickening of the airway wall； their lung function indicators， IL-10 level， and SOD content were significantly decreased； while the number of various inflammatory cells， IL-6 and TNF-α levels， MDA content， pathological score， as well as protein expressions of Muc5ac， Notch1 and GATA3 were significantly increased or upregulated （P＜0.05）. Compared with the AECOPD group， the pathological changes in the lung tissue of the rats in each plumbagin dose group were significantly alleviated， and the above quantitative indicators were significantly improved， and the improvement was more obvious in the plumbagin high- dose group （P＜0.05）. Jagged1 significantly reversed the protective effect of high-dose plumbagin on lung injury and related indicators in AECOPD rats （P＜0.05）. CONCLUSIONS Plumbagin can inhibit the inflammatory response and oxidative stress in the lungs of AECOPD rats， alleviate lung damage， and improve lung function. The above effects may be related to the inhibition of the Notch1/GATA3 signaling pathway.

Objective To evaluate whether Vibrio vulnificus secreted exotoxin-hemolysin (VVH) can activate platelet, an important blood immune cell, and to explore the possible molecular mechanism of platelet activation by VVH. Methods Transcriptomics and immunohistochemistry were used to analyze whether Vibrio vulnificus infection caused platelet activation in mice. Then, flow cytometry was used to identify whether VVH was the main stimulator of platelet activation. Naturally expressed VVH toxin was purified and prepared. The effects of extracellular and intracellular Ca²⁺ signal inhibitors on VVH activated platelets were evaluated by flow cytometry and Western blotting. The immune activation effect of VVH in the early stage of Vibrio vulnificus infection was analyzed in vivo. Results VVH was the main stimulator of platelet activation in Vibrio vulnificus culture supernatant. Natural VVH can induce the increase of P-selectin (CD62P) on platelet surface, the formation of platelet-neutrophil complex (PNC), and the release of platelet microvesicles. The activation mechanism may be related to the VVH pore-dependent Ca²⁺-calmodulin (CaM) -myosin light chain kinase (MLCK) signaling pathway, which led to the release of platelet alpha particles and cascade activation of platelets. In a mouse model of ALD infected by Vibrio vulnificus gavage, VVH was strongly associated with platelet activation. Conclusion This study shows that VVH is an important platelet activating molecule in the early stage of Vibrio vulnificus infection, and its induction of platelet activation may be related to the pathogenic process.
Animals ; Platelet Activation/drug effects* ; Hemolysin Proteins/pharmacology* ; Vibrio vulnificus/metabolism* ; Mice ; Blood Platelets/drug effects* ; Vibrio Infections/immunology* ; P-Selectin/metabolism* ; Bacterial Proteins ; Female

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Pleural mesothelioma （PM） is a rare malignant tumor originating from the pleura. Most patients are already in the advanced stage at the time of diagnosis， resulting in a low overall survival rate. MicroRNA （miRNA）， as key regulators of tumor epigenetic modification， have an intertwined interactive network with PM drug resistance. The mechanisms of drug resistance in PM to chemotherapeutic drugs include increasing drug efflux， reducing drug intake， enhancing DNA repair， and altering drug targets. The mechanisms of resistance to targeted therapy drugs include activating alternative signaling pathways， establishing a favorable tumor microenvironment， and triggering epithelial-mesenchymal transition. MiRNA plays a key part in the aforementioned resistance mechanisms， with some miRNAs promoting the drug sensitivity of cancer cells， while others contribute to increased drug resistance. In light of these key regulatory functions， targeting the dysregulated expression of endogenous miRNAs in the process of resistance formation using miRNA antagonists or miRNA mimics may be an effective therapeutic strategy to reverse drug resistance in PM.

Objective To explore the risk factors for the occurrence of hypertension in middle-aged and elderly residents in China using the Cox regression analysis model and decision tree model, and compare the differences between the two methods. Methods The 2011-2015 China Health and Retirement Longitudinal Study data were used. The study investigated the risk factors for hypertension using both a multivariate Cox regression model and a decision tree model. Results The results showed that the incidence rate of hypertension between 2011-2015 was 22.79%. Both the Cox regression model and decision tree model identified age, education level, body mass index, and diabetes as risk factors for hypertension. The Cox regression model also identified drinking status as a risk factor, while the decision tree model identified gender and marital status as additional risk factors. The area under the curve (AUC) suggested that the Cox regression model and decision tree model had comparable ability to predict hypertension. Conclusions The risk factors for hypertension include gender, age, education level, marital status, alcohol consumption, body mass index, and history of diabetes. The effectiveness of the hypertension prediction model established based on Cox regression model and decision tree model results is not different.

Objective To investigate the efficacy of sakubatril valsartan combined with tolvaptan in the treatment of heart failure patients with reduced ejection fraction(HFrEF)and the effects on echocardiography and cardiovascular events.Methods According to the random number table method,400 patients with HFrEF admitted to the First People's Hospital from September 2017 to January 2022 were divided into the control group and the combination group with 200 cases each.Both groups were given conventional treatment,based on which the control group was given sacubitril valsartan and the combination group was given sacubitril valsartan combined with tolvaptan.The efficacy,echocardiographic indexes[left ventricular ejection fraction(LVEF),left ventricular end-diastolic internal diameter(LVEDD),left ventricular end-systolic internal diameter(LVESD)],myocardial injury indexes[serum brain natriuretic peptide(BNP),high-sensitivity troponin T(hs-CTnT),growth transforming factor-15(GDF-15)],urine output,neuroendocrine factors[antidiuretic hormone(ADH),angiotensin(PRA),angiotensin Ⅱ(Ang Ⅱ)],cardiovascular events and adverse effects were compared between the two groups.Results The total effective rate was 94.50%(189/200)higher in the combined group than 86.00%(172/200)in the control group(P＜0.05);LVEF was high-er in the combined group than in the control group after treatment,and LVEDD and LVESD were lower than in the control group(P＜0.05);BNP,hs-CTnT,GDF-15,ADH PRA,and Ang II were lower in the combined group than in the control group,and urine volume was higher than in the control group(P＜0.05);at 6-month follow-up after treatment,there were no statistically significant differences in the rehospitalization rate of heart failure,the incidence of non-fatal infarction,post-discharge cardiovascular mortali-ty and all-cause mortality in the combined group compared with those of the control group(P＞0.05);there were no statistically significant differences in the incidence of adverse events in the combined group compared with that of the control group(P＞0.05).Conclusion Sacubitril valsartan combined with tolvaptan is effective in treating HFrEF,by reducing myocardial inju-ry,promoting urination,and improving patients'cardiac function without increasing the risk of cardiovascular events and adverse reactions.

Objective To compare the accuracy of bedside lung ultrasound in emergency(BLUE)and combined cardiac-lung and additional ultrasound(CLAUS)for diagnosing the causes of acute dyspnea.Methods Totally 1 016 patients with acute dyspnea were retrospectively enrolled and divided into cardiogenic pulmonary edema group(n=268),pneumonia group(n=574),pneumothorax group(n=33),pulmonary embolism group(n=67)and CAD(chronic obstructive pulmonary disease/asthma/diaphragmatic dysfunction)group(n=74)according to the causes of acute dyspnea.The findings of CLAUS protocol were compared among groups,and the accuracy of BLUE and CLAUS protocol for diagnosing the causes of acute dyspnea were also compared.Results CLAUS showed that B-B and B-C were the most common modes in cardiogenic pulmonary edema group,while A-B/A-C/B-A/B-B/B-C/C-C modes were common in pneumonia group,and A-A mode was the most common in pneumothorax group,pulmonary embolism group and CAD group.Significant differences of the manifestations of pulmonary ultrasound,pleural feature of anterior chest wall,left/right cardiac insufficiency and abnormal inferior vena cava diameter were found among groups(all P＜0.05).The accuracy of BLUE and CLAUS protocol for diagnosing the causes of acute dyspnea was 86.91%(883/1 016)and 94.49%(960/1 016),respectively,the latter was higher than the former(χ2=34.587,P＜0.05).Conclusion CLAUS protocol could be used to effectively diagnose the causes of acute dyspnea,with higher accuracy than BLUE protocol.

Chronic atrophic gastritis is a common and frequent disease in clinical practice. The symptoms of this disease can be attributed to the categories of " gastric pain" and " plumpness" in traditional Chinese medicine,and its pathogenesis is closely related to the dysfunction of xuanfu,qi-fluids,and stomach collaterals. In this study,we systematically rationalize the historical origin of the xuanfu,qi-fluids,and stomach collaterals and the relationship between them. According to the structure,physiological function and pathological characteristics of " xuanfu-qi-fluids-stomach collaterals",combined with the evolution of the chronic atrophic gastritis disease process,xuanfu depression and closure is believed to be the direct cause of chronic atrophic gastritis occurrence. The disharmony between qi and fluids is the core of the progression of chronic atrophic gastritis. Collateral deficiency and toxin damage are the root causes of the progression of chronic atrophic gastritis. Based on the mechanism of "xuanfu depression and closure-the disharmony between qi and fluids-collateral deficiency and toxin damage",it is proposed to open the xuanfu,restore the pivotal mechanism,activate blood circulation and diuresis,propagate qi and fluids,and supplement deficiency to unblock collaterals. From the perspective of "xuanfu-qi-fluids-stomach collaterals ",a more systematic and comprehensive understanding of the dynamic development process of chronic atrophic gastritis can be achieved,which will provide new ideas for the treatment of this disease in traditional Chinese medicine.