ObjectiveTo investigate the ameliorative effect of Lianpo Yin on gastric mucosal injury in the rat model of bile reflux gastritis （BRG） and decipher the underlying mechanism based on the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway. MethodsThirty-six SPF-grade male Sprague-Dawley （SD） rats were randomized into blank， model， hydrotalcite （positive control drug， 0.20 g·kg^-1）， NF-κB inhibitor （BAY11-7082， 5.00 mg·kg^-1）， low-dose Lianpo Yin （LPY-L， 9.77 g·kg^-1）， and high-dose Lianpo Yin （LPY-H， 19.54 g·kg^-1） groups （n=6）. Except that the blank group was administrated with distilled water by gavage， the rats in the other groups were induced for the modeling of BRG by gavage with reflux fluid for 35 consecutive days. From the 2^nd week of modeling， each treatment group was administrated with the corresponding drugs by gavage 6 h after the end of daily reflux fluid gavage. The BAY11-7082 group received intraperitoneal injection. Meanwhile， the blank group and model group received an equal volume of distilled water by gavage. All interventions were performed for 28 consecutive days. During the experiment period， the general status of rats was observed and body mass changes were recorded， and the stomach index was calculated after the last administration. The histopathological changes of the gastric mucosa were observed under the light microscope after hematoxylin-eosin （HE） staining. The serum levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） were quantified by enzyme-linked immunosorbent assay （ELISA）. The protein levels of TLR4， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65） and IL-6 in the gastric mucosal tissue were determined by Western blot. The nuclear translocation of NF-κB p65 was observed by immunofluorescence （IF） staining. ResultsCompared with the blank group， the model group showed mental depression， retarded body weight gain （P<0.05， P<0.01）， an increased stomach index （P<0.01）， severely damaged gastric mucosal structure with massive inflammatory cell infiltration and intestinal metaplasia （P<0.01）， elevated serum levels of TNF-α and IL-6 （P<0.01）， up-regulated protein levels of TLR4， p-NF-κB p65/NF-κB p65， and IL-6 in the gastric tissue （P<0.01）， and evident nuclear translocation of NF-κB p65 （P<0.01）. Compared with the model group， all drug intervention groups showed improved general status of rats. The body mass of rats in the hydrotalcite group， LPY-L， and LPY-H groups increased （P<0.05）， while the average body mass of rats in the BAY11-7082 group was slightly higher than that in the model group at each time point. All drug intervention groups showed decreased stomach index （P<0.05， P<0.01）， alleviated pathological damage of gastric mucosa with reduced inflammatory cell infiltration （P<0.05， P<0.01）， and declined serum levels of TNF-α and IL-6 （P<0.01）. Hydrotalcite and LPY-L reduced the levels of TLR4 and IL-6 （P<0.05）， but had no significant effect on p-NF-κB p65. LPY-H down-regulated the protein levels of TLR4， p-NF-κB p65/NF-κB p65， and IL-6 and inhibited the nuclear translocation of NF-κB p65 （P<0.01）， with its effect equivalent to that of BAY11-7082 and superior to that of hydrotalcite and LPY-L. ConclusionLianpo Yin can effectively ameliorate gastric mucosal inflammatory injury in BRG rats by inhibiting the activation of the TLR4/NF-κB signaling pathway， reducing the release of downstream pro-inflammatory cytokines， and suppressing the nuclear translocation of NF-κB p65.

Objective To explore the mechanism of 1,25-dihydroxy vitamin D3[1,25(OH)2D3]in renal interstitial fibrosis mediated by nuclear factor κB(NF-κB)and inflammatory cytokines.Methods Taking the renal interstitial fibrosis model induced by transforming growth factor-β1(TGF-β1)as the research object,they were divided into blank group(HK-2 cells+complete culture medium),model group(5ng/ml TGF-β1 stimulated HK-2 cells for 48 hours),intervention group A[with 10-7mol/L 1,25(OH)2D3 intervention for 24 hours on the basis of model group],intervention group B[with 10-7mol/L 1,25(OH)2D3 intervention for 48 hours on the basis of model group]and intervention group C[with 10-7mol/L 1,25(OH)2D3 intervention for 72 hours on the basis of model group].The cell morphology,activity,protein expression and inflammatory factor levels of each group were observed and compared.Results The cell viability of model group was significantly lower than that of blank group(P＜0.05),the cell viability of intervention groups A,B and C was significantly higher than that of model group(P＜0.05).The protein expressions of p-NF-κBp65/NF-κBp65 and smooth muscle actin α(α-SMA),as well as the levels of interleukin-6(IL-6)and tumor necrosis factor α(TNF-α)in model group were significantly higher than those in blank group,while the protein expression of E-cadherin was significantly lower than that in blank group(P＜0.05).The protein expressions of p-NF-κBp65/NF-κBp65 and α-SMA,as well as the levels of IL-6 and TNF-α in intervention groups A,B and C were significantly lower than those in model group,while protein expression of E-cadherin was significantly higher than that in model group(P＜0.05).Among them,the change in intervention group A was the most significant.Conclusion 1,25(OH)2D3 can alleviate renal interstitial fibrosis by regulating the NF-κB signaling pathway and inflammatory cytokines,and 24 hours may be the optimal intervention time window.

Kidney stone is a common urological disorder with an increasing annual incidence，posing a heavy social burden. Previous studies have demonstrated that diverse cell death modalities，including ferroptosis and apoptosis，induce renal tubular epithelial cell injury and thereby promote kidney stone formation. Emerging evidence in recent years has further revealed that immune-inflammatory responses driven by interactions among renal microenvironment components also contribute to kidney stone pathogenesis. This review systematically summarizes current research advances on the mechanisms by which inflammatory cellular components（e.g.，macrophages，T cells），inflammatory mediators（e.g.，inflammasomes，cytokines），microbiota，and their synergistic interactions influence kidney stone development within the renal microenvironment.

Objective To investigate the risk factors of the infarct growth rate(IGR)in patients with acute anterior circulation large vessel occlusion.Methods This is a retrospective analysis of consecutive patients having acute anterior circulation large-vessel occlusion and being admitted to the Department of Neurointerventional Intervention,Central Hospital affiliated to Dalian University of Technology between September 2021 and July 2023.Patients were dichotomized into rapid and slow growth groups based on the median value of IGR,with 145 cases in each group.Univariate and multivariate Logistic regression models were used to analyze the risk factors of preoperative IGR.Results Multivariable Logistic regression analysis,after univariate screening,showed that hypertension(OR=2.27,95%CI:1.39-3.71),atrial fibrillation(OR=1.95,95%CI:1.22-3.12),and intracranial internal carotid artery occlusion(OR=1.98,95%CI:1.19-3.28)were risk factors of preoperative IGR(P<0.05).Hypertension,atrial fibrillation,and internal carotid artery occlusion all exhibited relatively low predictive value for IGR(P<0.05).The area under the curve for predicting IGR by combining these three factors was 0.642(95%CI:0.579-0.704),indicating a slight improvement in predictive performance,yet it remained relatively low.Conclusion Hypertension,atrial fibrillation,and proximal occlusion are risk factors of IGR in patients having acute anterior circulation large vessel occlusion.

Objective:To investigate the mechanisms by which calpain small subunit 1(CAPN4)regulates cisplatin resistance and cancer stem cell(CSC)stemness in lung adenocarcinoma,and to provide experimental evidence for reversing drug resistance through targeting CSC stemness.Methods:Tissue samples were collected from 10 lung adenocarcinoma patients who underwent surgical resection at Fujian Cancer Hospital from January 2023 to January 2024.Immunohistochemistry(IHC)stining was used to detect the differential expression of CAPN4 in five cisplatin-resistant and five cisplatin-sensitive lung adenocarcinoma tissues,followed with a histological scoring(H-score).CAPN4 gene expression-related survival analysis in lung cancer patients was conducted using The Cancer Genome Atlas(TCGA)database and Gene Expression Profiling Interactive Analysis(GEPIA)platform.Additionally,tissue samples from two cisplatin-resistant and two cisplatin-sensitive lung adenocarcinoma cases were collected to establish lung adenocarcinoma organoid(PDO)models.H-E and IHC staining were used to assess the morphological consistency between PDOs and the primary tumors.CAPN4 gene expression was silenced using lentivirus-mediated shRNA transduction.The expression levels of stem cell markers ALDH1A1,CD133,Nanog,and SOX9 were detected at both the gene and protein levels using quantitative polymerase chain reaction(qPCR)and Western blotting(WB),respectively.The sensitivity of CAPN4-knockdown PDOs to cisplatin was evaluated using the adenosine triphosphate(ATP)assay,and the apoptosis was assessed using the caspase-3 assay.Results:IHC results showed that CAPN4 protein expression was significantly upregulated in cisplatin-resistant lung adenocarcinoma tissues(P<0.05).TCGA cohort analysis revealed that high CAPN4 expression was significantly associated with poor prognosis(reduced OS)in lung adenocarcinoma patients(HR=1.4,P<0.05).PDOs derived from cisplatin-resistant patients exhibited significant upregulation in CAPN4 protein and stemness markers at both gene and protein levels(all P<0.05).Cisplatin sensitivity assays demonstrated that PDOs derived from cisplatin-resistant patients had significantly higher IC50 values than those from cisplatin-sensitive patients(P<0.05).After CAPN4 knockdown,the expression of stem cell makers in PDOs derived from cisplatin-resistant patients were significantly reduced,and their sensitivity to cisplatin was enhanced(P<0.05).Conclusion:Knockdown of CAPN4 reduces stem cell marker expression and enhances cisplatin sensitivity in lung adenocarcinoma PDOs,providing a potential therapeutic target for reversing cisplatin resistance in lung cancer.

Objective To investigate the risk factors of the infarct growth rate(IGR)in patients with acute anterior circulation large vessel occlusion.Methods This is a retrospective analysis of consecutive patients having acute anterior circulation large-vessel occlusion and being admitted to the Department of Neurointerventional Intervention,Central Hospital affiliated to Dalian University of Technology between September 2021 and July 2023.Patients were dichotomized into rapid and slow growth groups based on the median value of IGR,with 145 cases in each group.Univariate and multivariate Logistic regression models were used to analyze the risk factors of preoperative IGR.Results Multivariable Logistic regression analysis,after univariate screening,showed that hypertension(OR=2.27,95%CI:1.39-3.71),atrial fibrillation(OR=1.95,95%CI:1.22-3.12),and intracranial internal carotid artery occlusion(OR=1.98,95%CI:1.19-3.28)were risk factors of preoperative IGR(P<0.05).Hypertension,atrial fibrillation,and internal carotid artery occlusion all exhibited relatively low predictive value for IGR(P<0.05).The area under the curve for predicting IGR by combining these three factors was 0.642(95%CI:0.579-0.704),indicating a slight improvement in predictive performance,yet it remained relatively low.Conclusion Hypertension,atrial fibrillation,and proximal occlusion are risk factors of IGR in patients having acute anterior circulation large vessel occlusion.

Objective To explore the mechanism of 1,25-dihydroxy vitamin D3[1,25(OH)2D3]in renal interstitial fibrosis mediated by nuclear factor κB(NF-κB)and inflammatory cytokines.Methods Taking the renal interstitial fibrosis model induced by transforming growth factor-β1(TGF-β1)as the research object,they were divided into blank group(HK-2 cells+complete culture medium),model group(5ng/ml TGF-β1 stimulated HK-2 cells for 48 hours),intervention group A[with 10-7mol/L 1,25(OH)2D3 intervention for 24 hours on the basis of model group],intervention group B[with 10-7mol/L 1,25(OH)2D3 intervention for 48 hours on the basis of model group]and intervention group C[with 10-7mol/L 1,25(OH)2D3 intervention for 72 hours on the basis of model group].The cell morphology,activity,protein expression and inflammatory factor levels of each group were observed and compared.Results The cell viability of model group was significantly lower than that of blank group(P＜0.05),the cell viability of intervention groups A,B and C was significantly higher than that of model group(P＜0.05).The protein expressions of p-NF-κBp65/NF-κBp65 and smooth muscle actin α(α-SMA),as well as the levels of interleukin-6(IL-6)and tumor necrosis factor α(TNF-α)in model group were significantly higher than those in blank group,while the protein expression of E-cadherin was significantly lower than that in blank group(P＜0.05).The protein expressions of p-NF-κBp65/NF-κBp65 and α-SMA,as well as the levels of IL-6 and TNF-α in intervention groups A,B and C were significantly lower than those in model group,while protein expression of E-cadherin was significantly higher than that in model group(P＜0.05).Among them,the change in intervention group A was the most significant.Conclusion 1,25(OH)2D3 can alleviate renal interstitial fibrosis by regulating the NF-κB signaling pathway and inflammatory cytokines,and 24 hours may be the optimal intervention time window.

Kidney stone is a common urological disorder with an increasing annual incidence，posing a heavy social burden. Previous studies have demonstrated that diverse cell death modalities，including ferroptosis and apoptosis，induce renal tubular epithelial cell injury and thereby promote kidney stone formation. Emerging evidence in recent years has further revealed that immune-inflammatory responses driven by interactions among renal microenvironment components also contribute to kidney stone pathogenesis. This review systematically summarizes current research advances on the mechanisms by which inflammatory cellular components（e.g.，macrophages，T cells），inflammatory mediators（e.g.，inflammasomes，cytokines），microbiota，and their synergistic interactions influence kidney stone development within the renal microenvironment.

The study was aimed to assess the impact of Brucea javanica oil emulsion(BJOE)on the responsiveness of programmed death receptor-1(PD-1)monoclonal antibody to lung adenocarcinoma in mice.The experimental approach involved subcutaneously inoculating Lewis's lung adenocarcinoma(LLC)cells into C57BL/6 mice,which were then divided into four groups:model group,25 ml·kg-1 BJOE group,10 mg·kg-1 PD-1 group,and combination group(25 ml·kg-1 BJOE and 10 mg·kg-1 PD-1).Tumor volume,mass,and inhibition rate were evaluated;the apoptosis within tumor tissue was detected by TUNEL staining;CD4+and CD8+T cell proportions within tumor tissues were analyzed by flow cytometry;the levels of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and granzyme B in tumor tissue were measured by enzyme-linked immunosorbent assay(ELISA).Additionally,LLC cells were categorized into a control group and three BJOE treatment groups(10,30,50 μl·ml-1),and programmed death ligand 1(PD-L1)expression in tumor tissues and LLC cells were assessed by Western blotting.Data showed that as compared with the model group,PD-1 monoclonal antibody alone did not significantly alter tumor volume,tumor mass,CD4+and CD8+T cell proportions,cytokine levels(IFN-γ,TNF-α,Granzyme B),or apoptosis in lung cancer-bearing mice.However,BJOE treatment reduced tumor volume and mass,enhanced CD4+and CD8+T cell proportions,increased cytokine levels,and augmented apoptosis(all P<0.05).Furthermore,the combination therapy of BJOE and PD-1 monoclonal antibody yielded significantly greater reductions in tumor volume and mass,with heightened CD4+and CD8+T cell proportions,cytokine levels,and apoptosis compared to either treatment alone(all P<0.05).Both BJOE treatment and the combination therapy significantly upregulated PD-L1 protein expression in tumor tissues compared to the model or PD-1 monoclonal antibody groups(P<0.05).Similarly,BJOE treatment at all tested concentrations significantly increased PD-L1 protein expression in LLC cells as compared to the control group(P<0.05).In conclusion,BJOE could upregulate PD-L1 expression in LLC cells and enhance the sensitivity of lung adenocarcinoma-bearing mice to PD-1 monoclonal antibodies.

Objective:To understand the breastfeeding situation in the neonatal intensive care units (NICUs) in Qianxinan Prefecture, Guizhou Province, and to assess the knowledge, attitudes, and practices of doctors and nurses regarding breastfeeding, aiming to provide foundational data for improving breastfeeding quality.Methods:A questionnaire was developed to survey the knowledge, attitudes, and practices related to breastfeeding in NICUs. The questionnaire was divided into three dimensions: knowledge (seven items, total score of 7), attitudes (nine items, total score of 45), and practices (seven items, total score of 35). Lower scores indicated weaker recognition of breastfeeding. Additionally, five items were included to identify the most influential factors affecting breastfeeding. From November 25 to November 30, 2023, a survey was conducted among doctors and nurses with professional qualifications who had worked in the neonatal departments of nine hospitals in Qianxinan Prefecture for at least one year. Independent sample t-tests and Chi-square tests were used to compare the scores of doctors and nurses from different levels of hospitals and within the same level of hospitals across the three dimensions. Results:(1) Among the nine hospitals, three were tertiary grade A hospitals (referred to as "tertiary hospitals"), with 95.6% (43/45) of the doctors and 96.5% (110/114) of the nurses participating in the survey. Six were secondary grade A hospitals (referred to as "secondary hospitals"), with 95.0% (38/40) of the doctors and 97.6% (83/85) of the nurses participating. (2) All nine hospitals were baby-friendly hospitals and all had breastfeeding promotional materials. Six hospitals had NICUs that promoted breastfeeding, with an average NICU breastfeeding rate of 25.8% across the prefecture between year 2021 to 2023. (3) The proportion of doctors who had received breastfeeding training was higher than that of nurses within the same level of hospitals [tertiary hospitals: 69.8% (30/43) vs. 40.0% (44/110), χ 2=10.97, P=0.001; secondary hospitals: 47.4% (18/38) vs. 24.1% (20/83), χ 2=6.55, P=0.010], although the overall training rates were low. (4) In tertiary hospitals, doctors scored higher than nurses in the attitude dimension [(35.35±4.75) vs. (33.18±5.60) scores, t=－2.03, P=0.044] and also in the practice dimension [(26.98±3.00) vs. (25.60±3.75) scores, t=－2.17, P=0.032]. In secondary hospitals, the total knowledge dimension score of doctors was higher than that of nurses [(4.92±1.44) vs. (4.20±1.45) scores, t=－2.52, P=0.013]. In tertiary hospitals, the total scores for attitude and practice dimensions of doctors were higher than those of doctors in secondary hospitals, and the total scores for knowledge, attitude, and practice dimensions of nurses were higher than those of nurses in secondary hospitals (all P<0.05). (5) In the knowledge dimension, the lowest scoring item of doctors in the tertiary hospitals was "Breastfeeding is possible for maternal hepatitis B newborns after receiving vaccines and immunoglobulin"; the lowest scoring item of nurses in the tertiary hospital, and doctors and nurses in the secondary hospitals was "The duration of breastfeeding has a greater impact on neonatal outcomes". In the attitude dimension, the lowest scoring item for doctors and nurses in both tertiary and secondary hospitals was "You think the breastfeeding process is more troublesome than feeding preterm formula". In the practice dimension, the lowest scoring item of the doctors and nurses in the tertiary hospitals was "Your hospital had enough breastfeeding knowledge training", while for the doctors and nurses in the secondary hospitals were "You have more opportunities to participate in various breastfeeding-related training" and "Breast feeding should be started as soon as possible when the infant is stable after active treatment", respectively. (6) The most influential factors affecting breastfeeding were: lack of cooperation from parents (50.0%, 137/274), relative insufficient human resources for doctors and nurses (21.9%, 60/274), and the absence or poor implementation of breastfeeding management policies (18.3%, 50/274), etc. Conclusions:The breastfeeding rate in NICU of county-level hospitals is relatively low, and medical staff, especially nurses, have insufficient knowledge about breastfeeding. It is necessary to strengthen various breastfeeding training for medical staff to enhance their understanding of NICU breastfeeding.