Background The pathogenesis of silicosis has not been fully elucidated, and microRNAs (miRNA) may be involved in the occurrence and development of silicosis. Objective To investigate the effect of miR-204-3p inhibitor on the epithelial-mesenchymal transition (EMT) process and silicosis fibrosis in silicon dioxide dust-induced alveolar epithelial cells. Methods A co-culture model of macrophages and epithelial cells was established using a Transwell chamber. NR8383 macrophages were seeded into the upper chamber of the Transwell, and RLE-6TN cells were seeded into the lower chamber. After 24 h of culture, the medium in the lower chamber was discarded, washed three times with phosphate-buffered saline (PBS), and replaced with serum-free medium. The cells were divided into four groups: control group, silicosis group, miRNA NC group, and miR-204-3p inhibitor group. The lower chamber was transfected with miRNA NC for the miRNA NC group or the miR-204-3p inhibitor for the miR-204-3p inhibitor group. The lower chambers of the remaining two groups were added by equal amounts of serum-free medium. After 24 h, except for the control group that received an equal volume of serum-free medium, the upper chambers of the remaining three groups were treated with 800 μg·mL⁻¹ silicon dioxide dust. Morphological changes in each group were observed under a microscope. The mRNA and protein expression levels of EMT-related factors, including α-smooth muscle actin (α-SMA), Vimentin, N-Cadherin, and E-Cadherin, were detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. The mRNA and protein expression levels of fibrosis-related factors, including Collagen I, Collagen III, and Fibronectin, were also assessed by RT-qPCR and Western blot. The fluorescence expression intensities of α-SMA, N-Cadherin, and E-Cadherin were evaluated by immunofluorescence. Results The morphological observation revealed that RLE-6TN cells in the control group exhibited a regular oval shape. After treatment with silicon dioxide, the cells predominantly displayed a long spindle shape. Following the intervention with the miR-204-3p inhibitor, the number of long spindle-shaped cells increased, and the intercellular gaps widened. The RT-qPCR results showed that, compared with the control group, the silicosis group exhibited significantly higher relative mRNA expression levels of EMT-related markers (α-SMA, Vimentin, and N-Cadherin) (P<0.05), while the relative mRNA expression level of E-Cadherin was significantly reduced (P<0.05); the relative mRNA expression levels of fibrosis-related markers (Collagen I, Collagen III, and Fibronectin) were also significantly elevated (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group showed significantly increased relative mRNA expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), decreased E-Cadherin mPNA expression (P<0.05), and elevated mPNA expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The Western blot analysis indicated that, compared with the control group, the silicosis group had significantly higher protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), lower E-Cadherin protein expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited significantly elevated protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), reduced E-Cadherin expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The immunofluorescence analysis demonstrated that, compared with the control group, the silicosis group showed enhanced fluorescence intensities of α-SMA and N-Cadherin and reduced fluorescence intensity of E-Cadherin. Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited increased fluorescence intensities of α-SMA and N-Cadherin and decreased fluorescence intensity of E-Cadherin. Conclusion The miR-204-3p inhibitor may exacerbate the EMT process and silicosis fibrosis in silicon dioxide-induced RLE-6TN cells. miR-204-3p plays a negative regulatory role in silicosis fibrosis.

Background Long-term exposure to free silica particles will lead to fibrosis of lung tissue, and abnormal expression of microRNA (miRNA) may affect the occurrence and process of fibrosis. Objective To observed possible intervention effect of miR-204-3p overexpression adenovirus on silicosis fibrosis induced by silica dust using a silicosis rat model via non-exposed intratracheal instillation. Methods Forty SD rats were randomly divided into four groups: control group, silicosis model group, miRNA-NC group, and miR-204-3p intervention group. Under ether anesthesia, rats in the silicosis model group, miRNA-NC group, and miR-204-3p intervention group were injected with 1 mL (50 mg·mL⁻¹) of free silica dust suspension into the trachea, while the control group was injected with the same volume of normal saline. After 30 d of dust exposure, the miR-204-3p intervention group was injected with rno-mir-204 adenovirus vector to overexpress miR-204-3p, and the miRNA-NC group was given empty virus vector. After 30 d of normal feeding, the animals were sacrificed by chloral hydrate anesthesia, and the lung tissue was taken for subsequent experiments. The relative expression level of miR-204-3p in lung tissue of rats in each group was detected by real-time fluorescence quantitative PCR (RT-qPCR). HE staining, Masson staining, and Sirius red staining were used for pathological observation. Immunohistochemistry was used to detect the expression of Fibronectin and Collagen I in lung tissue of rats in each group. RT-qPCR was used to detect the relative gene expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. Western blot was used to detect the protein expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. Results The anatomical features of lung tissue in the control group were pink lung tissue with soft texture and smooth surface, while those in the silicosis model were grayish white tissue with hard texture and scars and grayish white silicon nodules on the surface. Compared with the silicosis model group, the color of lung tissue in the miR-204-3p intervention group became ruddy, the surface was smooth, and the texture became soft. The staining results showed that the alveolar wall of the control group was thin, there were a small number of capillaries in the alveoli, and the alveolar structure was clear and complete. In the silicosis model group, the alveolar wall became thicker, the pulmonary septum was partially broken, the alveolar structure was defective, and a large amount of collagen fibers were deposited. The alveolar structure of the miR-204-3p intervention group was relatively clear and there was a small amount of collagen fiber deposition. RT-qPCR results showed that compared with the control group, the relative expression levels of miR-204-3p in lung tissue of the silicosis model group and the miRNA-NC group were decreased (P<0.05), and the relative expression level of miR-204-3p in lung tissue of the miR-204-3p intervention group was increased (P＜0.05). The results of immunohistochemistry showed that compared with the control group, the expression levels of Fibronectin and Collagen I in lung tissue of the silicosis model group were increased (P＜0.05). Compared with the silicosis model group, the relative expression levels of Fibronectin and Collagen I in lung tissue of the rats in the miR-204-3p intervention group were significantly decreased (P<0.05). The results of RT-qPCR and Western blot showed that compared with the control group, the relative protein and gene expression levels of fibrosis factors Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of the silicosis model group increased (P＜0.05). Compared with the silicosis model group, the relative gene and protein expression levels of fibrosis factors Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in the miR-204-3p intervention group were decreased (P＜0.05). Conclusion Silica dust can cause lung fibrosis in rats, and overexpression of miR-204-3P in vivo can reduce silicosis fibrosis in rats caused by silica dust.

Objective To explore the effect of sorafenib on HeLa cell proliferation by inducing cell apoptosis and autophagy and its impact on drug resistance.Methods The drug-resistant cell strains were constructed through in-termittent induction method,with concentrations of 0,2.5,5.0,7.5,10.0,15.0,20.0 μmol/L.HeLa cells were incubated with increasing concentrations of sorafenib with each concentration for 1 week.The drug-resistant cell strains with stable passages were collected.MTT assay was used to detect the effect of sorafenib on cell prolifer-ation.Cell cycle distribution was analyzed by flow cytometry.The change in the expression of drug-resistant and ap-optotic genes in the parents and drug-resistant cell strains under different drug concentrations was examined by semi-quantitative PCR.The changes of apoptotic related marker proteins LC3-Ⅰ and LC3-Ⅱ were detected by Westernblot.Results Stable drug-resistant strains were successfully obtained;Drug-treated cells were more blocked in the G1 phase.In drug-resistant cells,the expression of apoptosis suppressor gene Bcl-2 was significantly decreased and the apoptotic gene Bax as well as the drug-resistant genes were all significantly increased(P＜0.05).The LC3-Ⅱ/LC3-Ⅰ ratio of drug-resistant cells was significantly higher than that of parent cells(P＜0.05).Conclusions Sorafenib may block the cell cycle,suppress malignant cell proliferation and promote autophage.On one hand,autophagy participates in the development of cell drug resistance and promotes cell survival.On the other hand,drug-induced autophagy may activate some of apoptotic signaling pathway in drug-resistant cells and promote the reversal of cell drug resistance.

Acute kidney injury (AKI) is a devastating complications of end-stage of liver disease (ESLD), seriously affecting the prognosis of patients. With the deepening understanding of the pathogenesis, the definition, staging, diagnosis and treatment of ESLD with AKI have been gradually optimized. This article reviews the evolution of definition, pathogenesis, diagnosis and treatment of ESLD with AKI, to provide reference for early recognition, precise diagnosis and standardized treatment of this condition.

Objective To evaluate the short-term clinical effect of arthroscopic repair of rotator cuff injury with all-suture anchor using a prospective and single-cohort clinical trial.Methods Twenty-five patients with rotator cuff injuries(1.5 cm0.05).Conclusion Arthroscopic rotator cuff repair with all-suture anchor is feasible and safe,and has good short-term clinical effect.

Objective To explore the effect of nimodipine combined with minimally invasive puncture on neurological function,hemodynamics,and serum inflammatory factor levels in patients with hypertensive intracerebral hemorrhage(HICH).Methods A total of 108 patients with HICH treated at the Second Affiliated Hospital of Hebei North University from June 2019 to May 2022 were selected as the research subjects.They were divided into an observation group(n=55)and a control group(n=53)according to the treatment method.All patients in the two groups received minimally invasive puncture;on this basis,the patients in the observation group were treated with nimodipine for one month.The neurological deficit of patients in the two groups was evaluated by the National Institute of Health Stroke Scale(NIHSS)score before and after treatment.Before and after treatment,5 mL of fasting venous blood was taken from patients in the morning,and the serum was obtained by centrifugation.The serum levels of brain-derived neurotrophic factor(BDNF),neuron-specific enolase(NSE),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by enzyme-linked immunosorbent assay.Ultrasonic transcranial Doppler blood flow analyzer was used to monitor the hemodynamic indexes such as mean blood flow velocity(Vm),resistance index(RI)and pulsitility index(PI)of patients in the two groups before and after treatment.The adverse reactions such as headache,dizziness,infection and rebleeding were recorded in the two groups after treatment.Results There was no statistically significant difference in the NIHSS score and serum NSE and BDNF levels between the two groups before treatment(P＞0.05).After treatment,the NIHSS score and serum NSE level of patients in the two groups were significantly lower than those before treatment,while the serum BDNF level was significantly higher than that before treatment(P＜0.05).After treatment,the NIHSS score and serum NSE level of patients in the observation group were significantly lower than those in the control group,while the serum BDNF level was significantly higher than that in the control group(P＜0.05).There was no statistically significant difference in the Vm,PI and RI between the two groups before treatment(P＞0.05).After treatment,the Vm and PI of patients in the two groups were significantly higher than those before treatment,while the RI was significantly lower than that before treatment(P＜0.05).After treatment,the Vm and PI of patients in the observa-tion group were significantly higher than those in the control group,while the RI was significantly lower than that in the control group(P＜0.05).There was no statistically significant difference in serum TNF-α,IL-6,and CRP levels between the two groups before treatment(P＞0.05).The levels of serum TNF-α,IL-6,and CRP of patients in the two groups after treatment were significantly lower than those before treatment(P＜0.05).After treatment,serum TNF-α,IL-6,and CRP levels of patients in the observation group were significantly lower than those in the control group(P＜0.05).The incidence of adverse reactions in patients in the control group and observation group was 7.55％(4/53)and 9.09％(5/55),respectively,and the difference in the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion Nimodipine combined with minimally invasive puncture can effectively improve the blood perfusion rate of HICH patients,reduce the degree of inflammatory response,and alleviate the patients'neurological function damage.

Purpose/Significance To achieve safe and efficient open sharing of health and medical data,and to stimulate the value of health and medical data elements.Method/Process Aiming at the current situation and problems of open sharing of health and medical data,an open sharing system of health and medical data is designed based on data integration governance,data asset management,data product supermarket,data sampling analysis and online sandbox analysis.Result/Conclusion The practice has proved that the system can effectively realize the collection,analysis,management and utilization of health and medical data.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

infC gene encodes the translation initiation factor IF3 in bovine Pasteuella multocida,but it whether or not regulation to the virulence and cross-protection in P.multocida is still not well understood.In this study,the infC gene mutant(△infC)derived from bovine P.multocida type A strain CQ2 was constructed using by homologous recombination method.Compared with wild strain,the △infC showed significant increasing in biofilm formation,but the capsule produc-tion,virulence and bacterial loading in organs were significant decreased,and the IL-1β secretion of mouse peritoneal macrophage increased.Along with the infC gene deletion,the expression of genes related to capsule synthesis and LPS synthesis and transport were significantly down-regulated,while that of genes related to biofilm synthesis and outer membrane protein were significantly up-regulated.The inactivated vaccines of wild type and mutant were prepared and mice were immu-nized twice then challenged with wild type strains,respectively.The immuno-protection rate of△in fC inactivated vaccine against bovine P.multocida type A,B and F were 100.0％,83.3％and 0.0％,respectively,and the immuno-protection rate that against rabbit type P.multocida was 33.3％.The results indicated that infC gene could affect the virulence of P.multocida by regula-ting the production of capsule and the expressions of virulence related factors,and the deletion of infC gene conferred a certain cross-protection property of strains.This study provided a certain foundation for the development of P.multocida vaccine.

Objective To explore the effect of Rhizoma corydalis on the immune escape of Epstein-Barr virus(EBV)positive gastric cancer cells and its mechanism of targeting CXCL17 to affect immune escape of EBV-positive gastric cancer cells.Methods GEO2R online analysis software was used to screen differentially expressed genes in EBV-positive gastric cancer tissues.EBV-negative AGS gastric cancer cells and EBV-positive SUN-719 gastric cancer cells were used for the experiments.RT-qPCR and Western blotting were used to detect the expression of CXCL17in EBV-negative and EBV-positive gastric cancer cells.Transfection of CXCL17 siRNA into EBV-positive gastric cancer cells,detection of PD-L1 expression through Western blotting,coculture of EBV-positive gastric cancer cells with T cells,detection of cell viability using the CCK-8 assay,and detection of cell apoptosis rate through flow cytometry were conducted.EBV-positive gastric cancer cells were treated with different concentrations of a Rhizoma corydalis extract(2,4,and 8 μg/mL).The expression of CXCL17and PD-L1 was detected through Western blotting,and EBV-positive gastric cancer cells were cocultured with T cells.Cell viability was determined using CCK-8,and cell apoptosis rate through flow cytometry.The CXCL17overexpression plasmid was transfected into EBV-positive gastric cancer cells treated with Rhizoma corydalis extract(8μg/mL).The expression of PD-L1 and p-AMPK was detected through Western blotting,and EBV-positive gastric cancer cells were cocultured with T cells.Cell viability was determined using CCK-8,and cell apoptosis rate with flow cytometry.Results CXCL17 expression was upregulated in EBV-positive gastric cancer tissues and cells(P<0.05).Silencing of CXCL17reduced the expression of PD-L1 in EBV-positive gastric cancer cells,inhibited the proliferation of EBV-positive gastric cancer cells cocultured with T cells,and promoted cell apoptosis(P<0.05).Rhizoma corydalis treat-ment reduced the expression of CXCL17 and PD-L1 in EBV-positive gastric cancer cells,inhibited the proliferation of EBV-positive gas-tric cancer cells cocultured with T cells,and promoted apoptosis(P<0.05).Overexpression of CXCL17reversed the inhibitory effect of the Rhizoma corydalis treatment on PD-L1 expression and cell proliferation in EBV-positive gastric cancer cells,as well as the promoting effect of cell apoptosis(P<0.05).Overexpression of CXCL17also reduced the expression of p-AMPK in EBV-positive gastric cancer cells treated with Rhizoma corydalis(P<0.05).Conclusion CXCL17 expression is upregulated in EBV-positive gastric cancer cells,and Rhizoma corydalis inhibits immune escape in gastric cancer cells by downregulating CXCL17 expression in EBV-positive gastric cancer cells,which may be related to the activation of the AMPK signaling pathway.