As a coagulase-negative staphylococcus， Staphylococcus lugdunensis has stronger virulence and pathogenicity than other Staphylococcus bacteria and is comparable to Staphylococcus aureus. In recent years， there has been a gradual increase in the number of related case reports， A patient with hepatitis B cirrhosis and Staphylococcus lugdunensis bloodstream infection was admitted to our department and was followed up for more than 2 years， and the patient was analyzed in terms of clinical features， pathogenicity， invasion， and the application of related antibiotics.

OBJECTIVES: Neuropathic pain (NP) is one of the most common forms of chronic pain, yet current treatment options are limited in effectiveness. Peripheral nerve injury activates spinal microglia, altering their inflammatory response and phagocytic functions, which contributes to the progression of NP. Most current research on NP focuses on microglial inflammation, with relatively little attention to their phagocytic function. Early growth response factor 2 (EGR2) has been shown to regulate microglial phagocytosis, but its specific role in NP remains unclear. This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP, with the goal of identifying potential therapeutic targets. METHODS: Adult male Sprague-Dawley (SD) rats were used to establish a chronic constriction injury (CCI) model of the sciatic nerve. Pain behaviors were assessed on days 1, 3, 7, 10, and 14 post-surgery to confirm successful model induction. The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. Adeno-associated virus (AAV) was used to overexpress EGR2 in the spinal cord, and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP. CCI and lipopolysaccharide (LPS) models were established in animals and microglial cell lines, respectively, and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays. After confirming the involvement of microglial phagocytosis in NP, AAV was used to overexpress EGR2 in both in vivo and in vitro models, and phagocytic activity was further evaluated. Finally, eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify potential downstream effectors of EGR2. RESULTS: The CCI model successfully induced NP. Following CCI, EGR2 expression in the spinal cord was upregulated in parallel with NP development. Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats. Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis, which was further amplified by EGR2 overexpression. Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation. Among them, Lag3 emerged as a potential downstream target of EGR2. CONCLUSIONS EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.
Animals ; Microglia/metabolism* ; Phagocytosis/physiology* ; Rats, Sprague-Dawley ; Neuralgia/physiopathology* ; Early Growth Response Protein 2/metabolism* ; Male ; Rats ; Spinal Cord/metabolism* ; Sciatic Nerve/injuries*

Objective:To evaluate the effectiveness of an integrated management model involving the Centers for Disease Control and Prevention (CDC), general hospitals, and community health service centers in improving outcomes for community-dwelling patients with chronic obstructive pulmonary disease (COPD), with the aim of optimizing existing COPD management strategies.Methods:This study was a cluster randomized controlled trial. From January to March 2022, a total of 236 patients with COPD were recruited from four communities in Chibi City, Hubei Province. Ultimately, 223 patients completed follow-up and participated in the intervention evaluation. The participants were cluster-randomized into an intervention group ( n=121) and a control group ( n=102). The intervention group received a one-year "trinity" integrated community management model, while the control group received only basic follow-up. Face-to-face questionnaires were administered before and after the intervention to collect data on demographics, disease awareness, risk factors, respiratory symptoms, medication use, and disease management. Quality of life scores and pulmonary function tests were also assessed. Pre-and post-intervention outcomes were compared using t-tests or chi-square tests. Results:The intervention group demonstrated significantly higher rates of COPD awareness and disease-related knowledge compared to the control group (94.12% vs 77.78% and 78.15% vs 49.49%; both P<0.05), along with lower overall smoking rate and current smoking rate (57.14% vs 70.71% and 29.41% vs 47.47%; both P<0.05). The intervention group showed reduced household polluting fuel use for heating (17.65% vs 28.93%; P<0.05), while the control group exhibited no significant change. Significant improvements were observed in the intervention group for inhaler medication usage (14.05% vs 2.94%), exercise training, and respiratory muscle training (22.31% vs 2.94% and 26.45% vs 0.98%)(all P<0.05). Additionally, the intervention group reported lower prevalence of chronic sputum production, wheezing, and dyspnea (12.40%, 0.83%, 27.27% vs 24.51%, 9.80%, 41.18%; all P<0.05) compared to controls. Pulmonary function tests revealed that the percentage of forced expiratory volume in one second (FEV 1%predicted) was significantly higher in the intervention group than in the control group [(69.53±18.01)% vs (54.90±12.39)%; both P<0.05]. Conclusions:The "trinity" integrated management model effectively enhances health literacy, self-management capabilities, and quality of life among COPD patients, while reducing behavioral risk factors. This model aligns with the long-term and individualized management needs of COPD patients.

Objective To explore the effects of the Otago Exercise Program(OEP)on activities of daily living,muscle strength,balance,and physical function in older adults with sarcopenia,to compare OEP with conventional exercise training,and to provide a basis for clinical rehabilitation programs for older adults with sarcopenia.Methods In this randomized controlled trial,120 older adults clinically diagnosed with sarcopenia were enrolled.The participants were randomly assigned to the OEP intervention group(experimental group)and the conventional exercise intervention group(control group),with 60 in each group.The experimental group underwent 12 weeks of OEP training,three times a week,with each session lasting 45 minutes.The control group underwent conventional exercise training following the same schedule.The Modified Barthel Index was used as the primary outcome measure to assess activities of daily living.Secondary outcome measures included muscle strength,gait stability,dynamic balance,and physical function status,evaluated using grip strength,6-meter walking speed,the Timed Up and Go Test(TUGT),and the Short Physical Performance Battery(SPPB).Results A total of 120 older adults with sarcopenia were included.The mean age of the participants was(80.17±8.48)years.Baseline data before treatment showed no statistically significant differences between the two groups.Both groups completed the treatment within 12 weeks without experiencing any adverse events.The baseline data for the experimental group were as follows,MBI at(67.00±22.76)points,hand grip strength at(15.29±4.94)kg,gait speed at(0.61±0.26)m/s,TUGT time at(15.05±6.74)s,and SPPB score at(6.17±1.40)points,while the corresponding post-intervention findings were as follows,(78.72±15.83)points,(17.67±5.83)kg,(0.77±0.28)m/s,(13.49±6.16)s,and(9.25±1.71)points,respectively.The experimental group showed improvements in all measures from baseline to post-intervention(P＜0.05 for all measures).As for the control group,the baseline data for the corresponding measures were as follows,(67.20±22.12)points,(15.00±5.35)kg,(0.58±0.23)m/s,(17.29±6.90)s,and(6.00±1.24)points,respectively.The post-intervention findings increased to(71.13±20.28)points,(15.47±5.72)kg,(0.64±0.28)m/s,(16.50±6.99)s,and(6.73±1.61)points,respectively,but the changes were not statistically significant(P＞0.05).Furthermore,an intergroup comparison of intervention effects(post-intervention minus preintervention)revealed significant differences in mean changes from baseline.The experimental group demonstrated improvements of(+11.72±6.32)points in modified Barthel Index,(+11.72±6.32)kg in grip strength,(+0.16±0.09)m/s in gait speed,(—1.56±1.32)s in TUGT time,and(—1.56±1.32)points in SPPB score.In contrast,the control group showed smaller changes of(+3.93±5.65)points,(+0.47±1.37)kg,(+0.06±0.07)m/s,(—0.79±1.54)s,and(+0.73±1.12)points,respectively(all P＜0.05).Intergroup comparisons revealed superior outcomes in the experimental group across all measures.Conclusion OEP significantly enhances activities of daily living,improves muscle strength,balance,and physical function in older adults,and is more effective than conventional rehabilitation exercise programs,making it suitable for extensive clinical application.

Objective To investigate the effect of obstructive sleep apnea(OSA)on behavioral problems in children and the association between them.Methods A simple random sampling method was used to select 100 children aged 4 to 12 years for the case group.All of them were diagnosed with OSA through overnight polysomnography at the Sleep Medicine Center,West China Fourth Hospital,Sichuan University between October 2022 and October 2023.An additional 100 children without snoring symptoms and clinically evaluated and confirmed as not having OSA were enrolled as the control group.General demographic data of the participants were collected.The Caregiver Report Form of the Achenbach Child Behavior Checklist(CBCL)was used for behavioral problem assessment,and polysomnography data were collected.The chi-square/t test was used to analyze the inter-group differences in general data,the total score of behavioral problems,and scores for each dimension.Linear regression was performed to analyze the relationship between OSA and the total score for children's behavioral problems and those for the different dimensions.Logistic regression was applied to analyze the relationship between the obstructive apnoea-hypopnea index(OAHI)and behavioral problems in children with OSA.A logistic regression model integrating the OAHI×sex interaction term was constructed to evaluate the moderating effect of sex on the association between OAHI and behavioral problems.Results No significant differences were observed in general demographic data between the case and control groups.The total score for behavioral problems and those for each dimension were higher in the case group than those in the control group,with the total score of the case group being 24.60±1.55 and that of the control group being 8.85±0.75(P<0.001).The results of the linear regression analysis showed a positive association between OSA and both the total score for behavioral problems(b=16.01;95%CI,12.56-19.47)and those for each dimension.The results of the logistic regression analysis showed that,after adjusting for covariates,OAHI was a risk factor for behavioral problems in children with OSA(odds ratio[OR]=1.17;95%CI,1.04-1.31).After stratification by sex and adjustment for covariates,the OR value of the effect of OAHI on behavioral problems was slightly higher in female participants(1.57)than that in male participants(1.21).The interaction effect analysis showed that sex moderated the association between OAHI and behavioral problems(OR=1.64;95%CI,1.02-2.64;P=0.04).Conclusion Children with OSA are prone to developing behavioral problems.OAHI is a risk factor for behavioral problems in children with OSA,with a potentially greater effect observed in girls.

Objective To identify the key differentially expressed genes in the patients with lupus nephritis(LN)using bioinformatics methods and discover potential diagnostic biomarkers of LN for exploring the pathogenic mechanisms of LN.Methods The GSE99339 dataset related to chronic kidney disease was obtained from the Gene Expression Omnibus(GEO)database.Weighted gene co-expres-sion network analysis(WGCNA)was performed to identify the core modules highly correlated with LN.The differentially expressed genes(DEGs)between the two groups(32 LN patients and 14 healthy controls)from GSE32591 dataset were identified using Limma package.The intersection of DEGs and the LN-related module genes was obtained.The Gene Ontology(GO)function annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses of intersection genes were conducted using DAVID online tool to construct protein-protein interaction(PPI)network,and the key genes were screened using Cytoscape software.Boxplots and receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic efficiency of the key genes based on the the gene expression data of GSE112943 validation dataset.Results The greenyellow module(102 genes)was strongly correlated with LN(r=0.85,P＜0.01).A total of 361 DEGs were identified from GSE32591 dataset,among which 53 genes were found to intersect with the green-yellow module genes.The LN-related genes were mainly enriched in the biological processes and pathways which related to antiviral response,innate immunity,hepatitis C,and influenza A virus.The top five key genes in the PPI network were IFIT3,MX1,OAS1,RSAD2,and OAS3.The expression levels of 1FIT3,MX1,OAS1 and RSAD2 in LN were significantly different from con-trol groups(P＜0.05).ROC curve analysis showed that the AUC values for the four genes in predicting LN were all greater than 0.8,indicating high diagnostic efficiency.Conclusion IFIT3,MX1,OAS1 and RSAD2 may be the key differentially expressed genes in LN and may be potential diagnostic biomarkers and therapeutic targets for LN.

Objective To identify the key differentially expressed genes in the patients with lupus nephritis(LN)using bioinformatics methods and discover potential diagnostic biomarkers of LN for exploring the pathogenic mechanisms of LN.Methods The GSE99339 dataset related to chronic kidney disease was obtained from the Gene Expression Omnibus(GEO)database.Weighted gene co-expres-sion network analysis(WGCNA)was performed to identify the core modules highly correlated with LN.The differentially expressed genes(DEGs)between the two groups(32 LN patients and 14 healthy controls)from GSE32591 dataset were identified using Limma package.The intersection of DEGs and the LN-related module genes was obtained.The Gene Ontology(GO)function annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses of intersection genes were conducted using DAVID online tool to construct protein-protein interaction(PPI)network,and the key genes were screened using Cytoscape software.Boxplots and receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic efficiency of the key genes based on the the gene expression data of GSE112943 validation dataset.Results The greenyellow module(102 genes)was strongly correlated with LN(r=0.85,P＜0.01).A total of 361 DEGs were identified from GSE32591 dataset,among which 53 genes were found to intersect with the green-yellow module genes.The LN-related genes were mainly enriched in the biological processes and pathways which related to antiviral response,innate immunity,hepatitis C,and influenza A virus.The top five key genes in the PPI network were IFIT3,MX1,OAS1,RSAD2,and OAS3.The expression levels of 1FIT3,MX1,OAS1 and RSAD2 in LN were significantly different from con-trol groups(P＜0.05).ROC curve analysis showed that the AUC values for the four genes in predicting LN were all greater than 0.8,indicating high diagnostic efficiency.Conclusion IFIT3,MX1,OAS1 and RSAD2 may be the key differentially expressed genes in LN and may be potential diagnostic biomarkers and therapeutic targets for LN.

Objective:To evaluate the effectiveness of an integrated management model involving the Centers for Disease Control and Prevention (CDC), general hospitals, and community health service centers in improving outcomes for community-dwelling patients with chronic obstructive pulmonary disease (COPD), with the aim of optimizing existing COPD management strategies.Methods:This study was a cluster randomized controlled trial. From January to March 2022, a total of 236 patients with COPD were recruited from four communities in Chibi City, Hubei Province. Ultimately, 223 patients completed follow-up and participated in the intervention evaluation. The participants were cluster-randomized into an intervention group ( n=121) and a control group ( n=102). The intervention group received a one-year "trinity" integrated community management model, while the control group received only basic follow-up. Face-to-face questionnaires were administered before and after the intervention to collect data on demographics, disease awareness, risk factors, respiratory symptoms, medication use, and disease management. Quality of life scores and pulmonary function tests were also assessed. Pre-and post-intervention outcomes were compared using t-tests or chi-square tests. Results:The intervention group demonstrated significantly higher rates of COPD awareness and disease-related knowledge compared to the control group (94.12% vs 77.78% and 78.15% vs 49.49%; both P<0.05), along with lower overall smoking rate and current smoking rate (57.14% vs 70.71% and 29.41% vs 47.47%; both P<0.05). The intervention group showed reduced household polluting fuel use for heating (17.65% vs 28.93%; P<0.05), while the control group exhibited no significant change. Significant improvements were observed in the intervention group for inhaler medication usage (14.05% vs 2.94%), exercise training, and respiratory muscle training (22.31% vs 2.94% and 26.45% vs 0.98%)(all P<0.05). Additionally, the intervention group reported lower prevalence of chronic sputum production, wheezing, and dyspnea (12.40%, 0.83%, 27.27% vs 24.51%, 9.80%, 41.18%; all P<0.05) compared to controls. Pulmonary function tests revealed that the percentage of forced expiratory volume in one second (FEV 1%predicted) was significantly higher in the intervention group than in the control group [(69.53±18.01)% vs (54.90±12.39)%; both P<0.05]. Conclusions:The "trinity" integrated management model effectively enhances health literacy, self-management capabilities, and quality of life among COPD patients, while reducing behavioral risk factors. This model aligns with the long-term and individualized management needs of COPD patients.

Objective:To explore the mechanism by which miRNA-4469 (miR-4469) regulates the proliferation and invasion of renal cancer cells in vitro.Methods:The survival differences of patients with different expression levels of miR-4469 were analyzed based on the OncomiR database. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) method was used to detect the expression of miR-4469 in renal cancer cell lines ACHN, OS-RC-2, SK-RC-20, 769-P, A498 and normal renal tubular epithelial cell line HK-2, and the renal cancer cells with the lowest expression level of miR-4469 were divided into miR-4469 group and control group, and were transfected with miR-4469 mimic and negative control sequence, respectively. The CCK-8 assay was used to detect the cell proliferation ability (expressed as absorbance value) in the two groups, and Transwell assay was used to analyze the number of invasive cells in the two groups. TargetScan Release 8.0 software was used to predict the binding site between miR-4469 and protein disulfide isomerase A4 (PDIA4) mRNA, and dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-4469 and PDIA4 mRNA. qRT-PCR method was used to detect the expression of PDIA4 mRNA in cells of each group, and Western blotting method was used to detect the expression levels of PDIA4 protein and PI3K-AKT-m-TOR pathway proteins in cells of each group.Results:Analysis of relevant data from the OncomiR database showed that compared with patients with low miR-4469 expression, the overall survival of renal cancer patients with high miR-4469 expression was better ( P < 0.001). The relative expression of miR-4469 in each renal cancer cell line was lower than that in HK-2 cells (all P < 0.05), and the expression of miR-4469 in 769-P cells was the lowest, which were selected to perform the subsequent experiments. The proliferation ability of 769-P cells in the miR-4469 group was lower than that in the control group ( P < 0.01). The number of 769-P cell invasions in the miR-4469 group were less than that in the control group [(19±3) cells vs. (64±7) cells, t = 5.44, P = 0.002]. Compared with the co-transfection of wild-type PDIA4 and miR-4469 negative sequence group, the relative luciferase activity of cells in the co-transfection of wild-type PDIA4 and miR-4469 mimic sequence group was lower (0.42±0.07 vs. 1.01±0.08, t = 5.74, P = 0.001); there was no statistical difference in cell luciferase activity between the co-transfected mutant PDIA4 and miR-4469 negative sequence group and the co-transfected mutant PDIA4 and miR-4469 mimic sequence group (0.99±0.11 vs. 1.02±0.11, t = 0.19, P = 0.001). The relative expression levels of PDIA4 mRNA in 769-P cells in the miR-4469 group were lower than that in the control group (0.98±0.23 vs. 7.19±2.23, t = 2.77, P = 0.032). Compared with the control group, the expression of PDIA4 protein and PI3K-AKT-m-TOR pathway-related p-PI3K, p-AKT, p-mTOR, and p-SGK1 proteins in 769-P cells in the miR-4469 group were all lower (all P < 0.05). Conclusions:miR-4469 may be related to the survival of renal cancer patients, and its expression is down-regulated in various renal cancer cell lines. miR-4469 may inhibit the proliferation and invasion of renal cancer 769-P cells by regulating the PI3K-AKT-m-TOR pathway through PDIA4.

BACKGROUND:Studies have shown that both Panax notoginseng saponins and concentrated growth factor can promote fracture healing,but there are few studies addressing their combined effects on fracture healing.Panax notoginseng saponins may accelerate fracture healing by promoting the release of concentrated growth factor-related factors over a certain period of time. OBJECTIVE:To study the effect of Panax notoginseng saponins on concentrated growth factor release and fracture healing in rats. METHODS:Eighteen 8-week-old Sprague-Dawley rats were numbered and randomly divided into three groups:Panax notoginseng saponins group,model control group and blank group.Panax notoginseng saponins group was fed with Panax notoginseng saponins for 2 weeks.Model control group was given 2 mL of normal saline for 2 weeks and blank group was fed normally.Concentrated growth factor was obtained by the centrifugation method both from the Panax notoginseng saponins group and model control group.After 1 week of normal feeding,all animals underwent modeling for femoral fracture.The Panax notoginseng saponins group and the model control group were implanted with autologous concentrated growth factor,and then the release concentration of growth factors at different time points(1 hour,1,3,5,7,9 and 11 days)were measured by ELISA.Fracture healing was assessed based on postoperative X-ray and hematoxylin-eosin staining of bone tissues. RESULTS AND CONCLUSION:Compared with the model control group,the Panax notoginseng saponins group had higher release concentrations of vascular endothelial growth factor A and transforming growth factor β at 7,9,and 11 days,Platelet-derived growth factor BB at 5,9,and 11 days,and basic fibroblast growth factor at 1-11 days(P<0.01).X-ray examinations indicated that fracture healing in the Panax notoginseng saponins group was better than that in the model control group,and fracture healing in these two groups was better than that in the blank group at 2 months after surgery.Hematoxylin-eosin staining results found that the constituent osteocyte density in the Panax notoginseng saponins group was greater than that in the model control group,and the constituent osteocyte density in these two groups was better than that in the blank group.These findings indicate that Panax notoginseng saponins can increase the concentration of concentrated growth factor-related factors.After intervention with Panax notoginseng saponins,concentrated growth factors are more advantageous in promoting fracture healing in rats.