To screen potential drugs for the treatment of acute Liver Injury(ALI)through network pharmacology and mitochondrial dynamics,and to investigate their actions and mechanisms.Based on the commonly utilized Liver Pure Tablets and Liver-Protecting Capsules in the market,a com-ponent library of liver disease drugs was screened and established.Pharmacological anchoring anal-ysis was carried out.Potential liver disease therapeutic drugs were screened out through molecular docking,and feedback verification was performed using animal experiments.Acute liver injury mouse models were established through excessive induction with acetaminophen(APAP),and the histopathological changes of liver tissues were examined.The protective effect of the drug on ALI was evaluated by detecting alanine aminotransferase(ALT),aspartate aminotransferase(AST),superoxide dismutase(SOD),catalase(CAT),glutathione(GSH),and malondialdehyde(MDA)using enzyme-linked immunosorbent assay(ELISA).qRT-PCR was employed to detect peroxi-some proliferator-activated receptor gamma coactivator 1-alpha(PPARG1A),mitofusin 1(MFN1),mitofusin 2(MFN2),dynamin-related protein 1(DRP1),optic atrophy 1 protein(OP A1),Steroid receptor coactivator(SRC),and advanced glycosylation end-product specific re-ceptor(AGER)to explore the protective mechanism of the drug on ALI.The result showed that Network pharmacology identified a total of 662 intersection targets of three types of prescription drugs and ALI.Eventually,72 core targets were screened out.Pathway enrichment analysis indi-cates that the potential mechanism might be associated with the lipid and atherosclerosis signaling pathways.The results of the relevant molecular docking indicate that the most likely optimal drug might be emodin(EMO).EMO ameliorated the pathological damage in mice with acute liver inju-ry,significantly decreased the contents of transferase factors ALT and AST,simultaneously in-creased the contents of antioxidant enzymes CAT,GSH and SOD,and reduced the content of oxi-dative metabolic end product MDA.It also upregulated the mRNA expression levels of MFN1、MFN2,OPA1,DRP1,SRC and PPARGC1A proteins in liver tissue,and inhibited the mRNA ex-pression level of AGER protein.The drug EMO,jointly screened out by network pharmacology through anchoring and molecular docking,might promote mitochondrial fusion metabolism,allevi-ate liver oxidative stress,and improve liver injury in ALI mice via the Lipid and atherosclerosis pathway.

To screen potential drugs for the treatment of acute Liver Injury(ALI)through network pharmacology and mitochondrial dynamics,and to investigate their actions and mechanisms.Based on the commonly utilized Liver Pure Tablets and Liver-Protecting Capsules in the market,a com-ponent library of liver disease drugs was screened and established.Pharmacological anchoring anal-ysis was carried out.Potential liver disease therapeutic drugs were screened out through molecular docking,and feedback verification was performed using animal experiments.Acute liver injury mouse models were established through excessive induction with acetaminophen(APAP),and the histopathological changes of liver tissues were examined.The protective effect of the drug on ALI was evaluated by detecting alanine aminotransferase(ALT),aspartate aminotransferase(AST),superoxide dismutase(SOD),catalase(CAT),glutathione(GSH),and malondialdehyde(MDA)using enzyme-linked immunosorbent assay(ELISA).qRT-PCR was employed to detect peroxi-some proliferator-activated receptor gamma coactivator 1-alpha(PPARG1A),mitofusin 1(MFN1),mitofusin 2(MFN2),dynamin-related protein 1(DRP1),optic atrophy 1 protein(OP A1),Steroid receptor coactivator(SRC),and advanced glycosylation end-product specific re-ceptor(AGER)to explore the protective mechanism of the drug on ALI.The result showed that Network pharmacology identified a total of 662 intersection targets of three types of prescription drugs and ALI.Eventually,72 core targets were screened out.Pathway enrichment analysis indi-cates that the potential mechanism might be associated with the lipid and atherosclerosis signaling pathways.The results of the relevant molecular docking indicate that the most likely optimal drug might be emodin(EMO).EMO ameliorated the pathological damage in mice with acute liver inju-ry,significantly decreased the contents of transferase factors ALT and AST,simultaneously in-creased the contents of antioxidant enzymes CAT,GSH and SOD,and reduced the content of oxi-dative metabolic end product MDA.It also upregulated the mRNA expression levels of MFN1、MFN2,OPA1,DRP1,SRC and PPARGC1A proteins in liver tissue,and inhibited the mRNA ex-pression level of AGER protein.The drug EMO,jointly screened out by network pharmacology through anchoring and molecular docking,might promote mitochondrial fusion metabolism,allevi-ate liver oxidative stress,and improve liver injury in ALI mice via the Lipid and atherosclerosis pathway.

BACKGROUND:Exercise has a regulatory effect on intestinal flora and glucose metabolism,but the effects of high-intensity intermittent exercise on intestinal flora and glucose metabolism in patients with type 2 diabetes mellitus are unclear. OBJECTIVE:To investigate the effects of high-intensity intermittent exercise on glucose metabolism and intestinal flora in patients with type 2 diabetes mellitus. METHODS:Eleven patients with type 2 diabetes mellitus were recruited,among which,two were lost to the follow-up and nine were finally enrolled.High-intensity intermittent exercise intervention was conducted 3 times per week for 6 continuous weeks.Fasting blood and fecal samples were collected before and after the intervention.Glucose metabolism indexes were detected in the blood samples,and intestinal flora was detected in the fecal samples.Changes in glucose metabolism indexes and intestinal flora indexes of the patients with type 2 diabetes mellitus before and after the intervention were compared. RESULTS AND CONCLUSION:After 6 weeks of high-intensity intermittent exercise intervention,fasting blood glucose and glycosylated serum protein levels in patients were significantly reduced(P<0.05),and fasting insulin,although not significantly changed,was decreased compared with before intervention.Alpha diversity analysis showed that the diversity(Shannon index),richness(Chao index)and coverage(Coverage index)did not change significantly.Venn diagrams showed that the relative abundance of Bacteroidetes,Actinobacteria,Proteobacteria,and Fusobacteria in the intestinal flora of the patients increased,and the relative abundance of Firmicutes decreased,and a significant decrease was seen in Ruminococcus_torques and Ruminococcus_gnavus in the Firmicutes,which were both positively correlated with the abnormalities of the glycemic metabolism-related indicators,as well as with other disease development.All these findings indicate that high-intensity intermittent exercise intervention has an improvement effect on the glycemic metabolism-related indexes of patients with type 2 diabetes mellitus,and the abundance of beneficial flora in the intestinal tract increases,and the abundance of harmful flora decreased,enhancing the stability of the intestinal flora in patients.

OBJECTIVES: Investigating the protective effect of naringenin (NAR) on the osteogenic potential of human periodontal ligament stem cells (hPDLSCs) under oxidative stress and its related mechanisms. METHODS: The oxidative damage model of hPDLSCs was established using hydrogen peroxide (H₂O₂) andthe hPDLSCs were treated with different concentrations of NAR and 0.5 μmol/L forkhead box protein O-1 (FOXO1) inhibitor AS1842856. After that, the cell counting kit-8 (CCK8) was used to determine the optimal concentrations of H₂O₂ and NAR. The alkaline phosphatase (ALP) staining and real time fluorescent quantitative reverse transcription polymerase chain reaction (qRT-PCR) were employed to assess the expression of ALP, runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) in hPDLSCs of each group. The enzyme-linked immunosorbent assay (ELISA) and 2',7'-dichlorofluorescin diacetate (DCFH-DA) staining were utilized to evaluate the expression of reactive oxygen species (ROS), malondialdehyde (MDA) and lactate dehydrogenase (LDH) in hPDLSCs. Meanwhile, qRT-PCR and western blot were used to detect the expression levels of FOXO1 and β-catenin, both are pathway related genes and proteins. RESULTS: H₂O₂ exposure led to an increase in oxidative damage in hPDLSCs, characterized by a rise in intracellular ROS levels and increased expression of MDA and LDH (P<0.05). At the same time, the osteogenic differentiation ability of hPDLSCs decreased, as evidenced by lighter ALP staining and reduced expression levels of osteogenic differentiation-related genes ALP, RUNX2 and OCN (P<0.05). Co-treatment with NAR alleviated the oxidative damage in hPDLSCs, enhanced their antioxidant capacity, and restored their osteogenic ability. The FOXO1 inhibitor AS1842856 downregulated the expression of β-catenin (P<0.05) and significantly diminished both the antioxidant effect of NAR and its ability to restore osteogenesis (P<0.05). CONCLUSIONS NAR can enhance the antioxidant capacity of hPDLSCs by activating the FOXO1/β-catenin signaling pathway within hPDLSCs, thereby mitigating oxidative stress damage and alleviating the loss of osteogenic capacity.
Humans ; Oxidative Stress/drug effects* ; Periodontal Ligament/cytology* ; Hydrogen Peroxide ; Forkhead Box Protein O1/metabolism* ; Stem Cells/cytology* ; Flavanones/pharmacology* ; beta Catenin/metabolism* ; Osteogenesis/drug effects* ; Signal Transduction ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Alkaline Phosphatase/metabolism* ; Osteocalcin/metabolism* ; Cells, Cultured ; Cell Differentiation/drug effects*

OBJECTIVES: This study aimed to investigate how naringenin (Nar) affected the anti-inflammatory, vascula-rization, and osteogenesis differentiation of human periodontal ligament stem cells (hPDLSCs) stimulated by lipopolysaccharide (LPS) and to preliminarily explore the underlying mechanism. METHODS: Cell-counting kit-8 (CCK8), cell scratch test, and Transwell assay were used to investigate the proliferation and migratory capabilities of hPDLSCs. Alkaline phosphatase (ALP) staining, alizarin red staining, lumen-formation assay, enzyme-linked immunosorbent assay, quantitative timed polymerase chain reaction, and Western blot were used to measure the expression of osteopontin (OPN), Runt-related transcription factor 2 (RUNX2), vascular endothlial growth factor (VEGF), basic fibroblast growth factor (bFGF), von Willebrand factor (vWF), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6. RESULTS: We observed that 10 μmol/L Nar could attenuate the inflammatory response of hPDLSCs stimulated by 10 μg/mL LPS and promoted their proliferation, migration, and vascularization differentiation. Furthermore, 0.1 μmol/L Nar could effectively restore the osteogenic differentiation of inflammatory hPDLSCs. The effects of Nar's anti-inflammatory and promotion of osteogenic differentiation significantly decreased and inflammatory vascularization differentiation increased after adding AMD3100 (a specific CXCR4 inhibitor). CONCLUSIONS Nar demonstrated the ability to promote the anti-inflammatory, vascularization, and osteogenic effects of hPDLSCs stimulated by LPS, and the ability was associated with the stromal cell-derived factor/C-X-C motif chemokine receptor 4 signaling axis.
Humans ; Anti-Inflammatory Agents/pharmacology* ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL12 ; Lipopolysaccharides/pharmacology* ; Osteogenesis ; Periodontal Ligament/metabolism* ; Receptors, Chemokine/metabolism* ; Stem Cells ; Interleukin-8/metabolism*

Objective:To assess the effectiveness of a model created using clinical features and preoperative chest CT imaging features in predicting the chronic obstructive pulmonary disease (COPD) among patients diagnosed with lung cancer.Methods:A retrospective analysis was conducted on clinical (age, gender, smoking history, smoking index, etc.) and imaging (lesion size, location, density, lobulation sign, etc.) data from 444 lung cancer patients confirmed by pathology at the Second Affiliated Hospital of Naval Medical University between June 2014 and March 2021. These patients were randomly divided into a training set (310 patients) and an internal test set (134 patients) using a 7∶3 ratio through the random function in Python. Based on the results of pulmonary function tests, the patients were further categorized into two groups: lung cancer combined with COPD and lung cancer non-COPD. Initially, univariate analysis was performed to identify statistically significant differences in clinical characteristics between the two groups. The variables showing significance were then included in the logistic regression analysis to determine the independent factors predicting lung cancer combined with COPD, thereby constructing the clinical model. The image features underwent a filtering process using the minimum absolute value convergence and selection operator. The reliability of these features was assessed through leave-P groups-out cross-validation repeated five times. Subsequently, a radiological model was developed. Finally, a combined model was established by combining the radiological signature with the clinical features. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves were plotted to evaluate the predictive capability and clinical applicability of the model. The area under the curve (AUC) for each model in predicting lung cancer combined with COPD was compared using the DeLong test.Results:In the training set, there were 182 cases in the lung cancer combined with COPD group and 128 cases in the lung cancer non-COPD group. The combined model demonstrated an AUC of 0.89 for predicting lung cancer combined with COPD, while the clinical model achieved an AUC of 0.82 and the radiological model had an AUC of 0.85. In the test set, there were 78 cases in the lung cancer combined with COPD group and 56 cases in the lung cancer non-COPD group. The combined model yielded an AUC of 0.85 for predicting lung cancer combined with COPD, compared to 0.77 for the clinical model and 0.83 for the radiological model. The difference in AUC between the radiological model and the clinical model was not statistically significant ( Z=1.40, P=0.163). However, there were statistically significant differences in the AUC values between the combined model and the clinical model ( Z=-4.01, P=0.010), as well as between the combined model and the radiological model ( Z=-2.57, P<0.001). DCA showed the maximum net benifit of the combined model. Conclusion:The developed synthetic diagnostic combined model, incorporating both radiological signature and clinical features, demonstrates the ability to predict COPD in patients with lung cancer.

Numerous studies have reported that the resistance of biofilm bacteria to antibiotics can be up to 10-1 000 fold higher than that of planktonic bacteria. Bacterial biofilms are reported to be responsible for more than 80% of human microbial infection, posing great challenges to the healthcare sector. Many studies have reported that plant extracts and their active ingredients can inhibit the formation and development of bacterial biofilms, including reducing biofilm biomass and the number of viable bacteria in biofilms, as well as eradicating mature biofilms. This review summarized the plant extracts and their active ingredients that are inhibitory to bacterial biofilms, and analyzed the underpinning mechanisms. This review may serve as a reference for the development of plant drugs to prevent and treat biofilm infections.
Anti-Bacterial Agents/pharmacology* ; Bacteria ; Biofilms ; Humans ; Plant Extracts/pharmacology* ; Quorum Sensing

Probiotics can improve the microecological balance of the body and have special effects in promoting nutrient absorption, controlling intestinal infections, and regulating immune function. However, there are problems such as difficult colonization in the gastrointestinal environment and low oral bioavailability. Bacterial biofilms are organized bacterial cells that adhere to an abiotic or biotic surface and are enclosed in extracellular polymeric substances of exopolysaccharides (EPS), extracellular DNA (eDNA), proteins and lipids, with a three-dimensional spatial structure. Probiotics with the help of bacterial biofilms have obvious advantages over planktonic bacteria in stress resistance, combating pathogens and modulating the host's immune function, which provides a new research idea for the development of probiotics. This paper expounded on the advantages of probiotics with the help of bacterial biofilms, and focused on introducing substances that could promote the formation of probiotic biofilms and the mechanisms, and the safety of probiotic biofilms. Currently, research on probiotic biofilms is still in its infancy, and this paper is expected to provide references for future research in this field.
Bacteria ; Biofilms ; Extracellular Polymeric Substance Matrix ; Probiotics

Objective:To investigate the relationship between genotype and phenotype in children with CRB1 mutated Leber congenital amaurosis (LCA) and early onset retinal dystrophy (EOSRD). Methods:A retrospective clinical study. From January 2013 to December 2019, 10 children with CRB1 mutated LCA/EOSRD were enrolled in the study. The patients were identified as CRB1 mutation by the second generation targeted capture sequencing, Sanger sequencing and the family segregation analysis. All children underwent electroretinogram (ERG) and fundus examination. At the same time, 6 cases were examined by optical coherence tomography (OCT); 1 case was examined by fluorescein fundus angiography (FFA), 7 cases were examined by wide-angle laser scanning ophthalmoscope (UWF SLO). Results:There were 6 cases of LCA and 4 cases of EOSRD in 10 patients with CRB1 gene mutations. The average age of first visit was 3.61 years old. The light and dark wave of ERG was flat in 6 cases, and decreased in 4 cases. A total of 19 pathogenic mutations were detected. There were 1 homozygous mutation and 9 compound heterozygous mutations. There were 4, 2 and 1 cases of "copper-coin" like, "salt and pepper" like and "osteocyte" like pigment changes in retina, 1 case of "crystalline pigment" change and 2 cases of macular pigment scar. In 7 cases of UWF SLO examination, different degrees of para-arteriolar pigment epithelium retention (PPRPE) were found in the middle and peripheral fundus. In 6 cases examined by OCT, the outer layer of retina atrophied and the band of ellipsoid disappeared. Symmetrical cystoid macular edema, splitting cystoid macular degeneration and adhesion of epi-macular membrane to optic disc and macular area were found in 1 case, respectively, the retinal structure was rough and thickened, and the fovea became thinner in 3 cases. In FFA examination, 1 case showed uveitis-like changes with late optic disc fluorescein staining, macular fluorescence accumulation, strong fluorescence diffusing along the blood vessels in each quadrant, peripheral PPRPE of "frost-branch" like strong fluorescence. Conclusion:The relationship between genotype and phenotype of CRB1 mutation is complex, and PPRPE is a common characteristic change.

Objective To get well-informed of the current status of emergency training in primary hospitals in Sichuan Province and to find weaknesses in the system in order to provide scientific basis for emergency knowledge and skills training.Methods A stratified random cluster sampling method as adopted and an anonymous questionnaire survey method was conducted to investigate the basic circumstances of the current training and the training needs of 1 000 emergency medical staff in 9 regions throughout Sichuan Province.Results The scope of the survey covered emergency doctors,nurses and technicians in hospitals of Grade Ⅱ,Grade Ⅲ and below.A total of 1 000 surveys were sent out and 983 were recovered.The questionnaire completion rate was 98.3％.The respondents mainly worked for more than 10 years,most of which with Bachelor degree,junior and intermediate titles.Results of the survey showed,63.1％ Most respondents have only one or two training opportunities per year.The training methods are mainly continuing education (59.0％,580 trips),training organized within the unit (58.5％,575 trips),and training organized by health administrative units (39.3％,386 trips).The main contents of the training are:basic professional skills learning (66.7％,655 trips),basic professional theoretical study (59.2％,582 trips),and new emergency technology (42.5％,418 trips),only 32.0％ of the respondents believe that these methods meet the practical needs.The main factors that influence participation in the training were:not be arranged by employer (36.2％,356 trips);the training was different from actual work (31.6％,311 trips);no replacement for work so they couldn't join training (29.8％,293 trips).The survey showed that the most desirable way of training is:practical application (60.1％,591 trips) and the most desirable training content is:emergency first aid knowledge (73.7％,724 trips).There were significant differences in case discussion,technical observation,academic lectures,special study trainingand learning methods in hospitals of different levels (P＜0.05),but there was no significant difference in the choice of professional practice methods (P＞0.05),and the selection of training contents was in emergency first aid knowledge,general medical knowledge and prevention and treatment of chronic diseases.There was no statistical difference in the selection of training contents of knowledge,infectious disease knowledge and department management knowledge (P＞0.05).There were significant differences in the choice of nursing knowledge training (P＜0.05).Conclusion The current situation showed a lack of first-aid knowledge and skills training for emergency personnel in Sichuan Province.The present situation of skill training can't satisfy the need of their desire to participate in training.It is urgent to develop a standardized,systematic and scientific training mode to improve the emergency first aid ability of primary medical and emergency personnel.