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 assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To evaluate long-term outcomes of endoscopic papillectomy (EP) for duodenal papillary adenomas and to identify risk factors for incomplete resection.Methods:Clinical data of 180 patients diagnosed as having duodenal papillary adenoma via postoperative pathology after EP in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2010 to December 2022 were retrospectively analyzed. Patients were divided into two groups based on their postoperative margin status: the complete resection group (negative resection margins) and the incomplete resection group (positive/uncertain resection margins). Recurrence rates were compared between the two groups, and logistic regression analysis was performed to identify risk factors for incomplete resection.Results:Among the 180 patients included in the study, 137 underwent complete resection, and 43 had incomplete resections. Recurrence rate was significantly higher in the incomplete resection group than that in the complete resection group (30.2% VS 15.3%, χ2=4.75, P=0.029). logistic regression analysis indicated that high-grade intraepithelial neoplasia was an independent risk factor for incomplete resection ( OR=2.43, 95% CI:1.12-5.26, P=0.024). Conclusion:Patients with incomplete resection after EP have a higher recurrence rate in the long-term follow-up. High-grade intraepithelial neoplasia is an independent risk factor for incomplete resection. Close surveillance and aggressive management are warranted for patients with positive or uncertain resection margins to mitigate the recurrence risk.

Objective To predict the hospitalization expense of pneumonia patients using the CatBoost and LightGBM models and explore associated influencing factors,providing a scientific basis for reasonable control of medical expenses and alle-viating the financial burden on society and patients'families.Methods Data from 1407 inpatients with pneumonia admitted to a tertiary hospital between November 1,2021 and January 31,2023 were collected from the hospital information system.The Cat-Boost and LightGBM models were employed to predict the hospitalization expenses of pneumonia patients and analyze the influen-cing factors.Results The full-variable CatBoost model fitted better than the full-variable LightGBM model,with the R-square value of 0.859 and Mean Absolute Percentage Error(MAPE)of 0.352.The full-variable CatBoost model predicted better than the full-variable LightGBM model,with the R-square value of 0.820 and MAPE of 0.363.Notably,the average length of stay was the most important factor affecting the hospitalization expenses of pneumonia patients.Conclusion Compared to the LightGBM model,the CatBoost model indicated more advantages and higher accuracy in predicting hospitalization expenses for pneumonia patients.These accurate predictions of hospitalization expenses can provide decision-making references for hospital administra-tors.Therefore,on the premise of ensuring medical quality,reasonably reducing the length of hospitalization can effectively con-trol the increase in hospitalization expenses.

Objective:To evaluate the efficacy of lamb′s tripe extract and vitamin B 12 capsule (LTEVB 12C) on chronic atrophic gastritis (CAG) at different locations (antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and corpus greater curvature). Methods:From August 2011 to January 2013, 715 patients with CAG in a multicenter, randomized, double-blind, placebo-controlled trial were enrolled from 16 tertiary first-class hospitals across the country, including the First Affiliated Hospital of Air Force Medical University, Nanfang Hospital of Southern Medical University, the First Hospital of Jilin University, West China Hospital of Sichuan University, etc., there were 476 cases in the LTEVB 12C group and 239 cases in the placebo group. The patients of the LTEVB 12C group received LTEVB 12C, and the patients of placebo group received LTEVB 12C mimetic, all the medications were taken 3 capsules each time and 3 times a day after meals, and the treatment course of 2 groups were both 6 months. The efficacy evaluation criteria included the effective rate (a decrease of ≥1 in histopathological score compared with baseline after 6 months of treatment) and the reversal rate (a decrease of ≥ 2 in histopathological score compared with baseline after 6 months of treatment in the patients with moderate to severe CAG). The impact of lesion sites on the therapeutic effects of LTEVB 12C was analyzed by logistic regression analysis. The two-way unordered Cochran-Mantel-Haenszel chi-square test considering the center effect and Pearson chi-square test were used for statistical analysis. Results:The effective rates of chronic inflammation at the antrum greater curvature and corpus greater curvature (23.3%, 110/473 vs. 13.0%, 31/239; 20.3%, 96/472 vs. 12.6%, 30/239), the effective rates of atrophy at the antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and the corpus greater curvature (27.0%, 118/437 vs. 15.7%, 34/216; 29.2%, 126/432 vs. 18.5%, 38/205; 27.8%, 121/435 vs. 16.7%, 36/216; 32.5%, 127/391 vs. 19.8%, 37/187; 33.0%, 119/361 vs. 21.8%, 39/179), and the effective rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (45.0%, 112/249 vs. 29.8%, 31/104; 53.8%, 86/160 vs. 33.9%, 21/62; 45.8%, 103/225 vs. 24.0%, 25/104; 51.9%, 83/160 vs. 28.3%, 17/60) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=10.76, 6.39, 9.69, 7.91, 11.05, 9.62, 8.57, 5.20, 7.11, 12.45, and 6.73; all P<0.05). The reversal rates of chronic inflammation at the corpus lesser curvature and corpus greater curvature (5.2%, 12/231 vs. 0, 0/123; 4.7%, 8/170 vs. 0, 0/88), the reversal rates of atrophy at the antrum lesser curvature, antrum greater curvature, corpus lesser curvature, and the corpus greater curvature (6.8%, 22/323 vs. 1.3%, 2/151; 9.2%, 29/315 vs. 1.4%, 2/144; 14.2%, 38/267 vs. 2.5%, 3/121; 20.8%, 35/168 vs. 5.8%, 4/69), and the reversal rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (29.8%, 39/131 vs. 9.1%, 4/44; 41.0%, 32/78 vs. 12.5%, 3/24; 33.3%, 44/132 vs. 4.8%, 3/63; 50.0%, 37/74 vs. 8.7%, 2/23) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=6.58, 5.12, 5.60, 8.61, 11.43, 6.59, 7.30, 4.95, 15.92, 7.62; all P<0.05). There were no statistically significant differences in the effective rates and reversal rates of active inflammation at different locations between the LTEVB 12C group and the placebo group (all P>0.05). The results of logistic regression analysis (taking the antrum lesser curvature as the reference) further confirmed that the reversal rates of chronic inflammation ( OR=0.22, 95% confidence interval (95% CI): 0.07 to 0.67; OR=0.24, 95% CI: 0.07 to 0.80), atrophy ( OR=0.28, 95% CI: 0.16 to 0.49; OR=0.28, 95% CI: 0.16 to 0.49), and intestinal metaplasia ( OR=0.42, 95% CI: 0.24 to 0.77; OR=0.20, 95% CI: 0.08 to 0.52) at the corpus lesser curvature and corpus greater curvature were all higher than those at the antrum lesser curvature, and the differences were statistically significant (all P<0.05). There were no statistically siginificant differences in the reversal rates of the aforementioned pathological features between the antrum greater curvature, gastric angle, and the antrum lesser curvature (all P>0.05). Conclusion:LTEVB 12C can achieve good efficacy in the treatment of CAG, and the chronic inflammation, atrophy, and intestinal metaplasia at multiple locations are improved, especially at the corpus lesser curvature and the corpus greater curvature.

Objective To investigate the effect of dexmedetomidine on the median effect concentration(EC50)of ropivacaine during sciatic nerve block combined with femoral nerve block in patients undergoing lower extremity surgery.Methods Patients with sciatic nerve block combined with femoral nerve block anesthesia who underwent lower extremity surgery from November 2021 to November 2023 were selected as the study objects.They were randomly divided into control group(0.9％saline),group D1(0.50 μg·kg-1 dexmedetomidine),group D2(0.75 μg·kg-1 dexmedetomidine)and group D3(1.00 μg·kg-1 dexmedetomidine).The stress response,serum pain mediators,vital signs and visual analogue scale(VAS)of patients at different time points during operation were analyzed by repeated measures ANOVA.ropivacaine EC50 was measured by sequential method,and the relationship between dexmedetomidine dose and ropivacaine EC50 was analyzed by Logistic regression.Results A total of 208 patients were include and each group was 52 patients.Compared with the same group before surgery,the stress response level of the 4 groups after surgery and 1 h after surgery was significantly decreased,and the serum pain mediators level was significantly increased(P＜0.05).Compared with the control group,the stress response and serum pain mediators levels in groups D1,D2 and D3 were more normal after surgery and 1 h after surgery,among them,group D3 was most close to the normal value(P＜0.05).There were no significant differences in blood oxygen saturation and bifrequency index of EEG among the four groups at each time point(P＞0.05).At T1 and T2,the heart rate(HR)of the control group was significantly higher than that of the group D2 and D3(P＜0.05).At T1,the control group had a significantly higher mean arterial pressure(MAP)than the other three groups,at T2,the control group had a significantly higher MAP than the group D2 and D3,and at T3,the control group had a significantly higher MAP than the group D3(P＜0.05).VAS scores in 4 groups were significantly lower after surgery and 1 h after surgery than before surgery(P＜0.05).The VAS score in group D3 was significantly lower than that in group D1 and D2(P＜0.05).Repeated measurement ANOVA showed that the effects of time on stress response and serum pain mediators were different with different anesthesia methods.The influence of time on HR,MAP and VAS scores varied with different anesthesia methods.Sequential assay results showed that the EC50 of ropivacaine in control group,group D1,group D2 and group D3 was 5.985,5.631,5.329 and 5.125 μg·mL-1,respectively.Logistic results showed that the dose of dexmedetomide was a protective factor for ropivacaine EC50 in sciatic nerve block combined with femoral nerve block in limb surgery patients(P＜0.05).Conclusion The ropivacaine EC50 can be significantly reduced by 1.00 μg·kg-1 dexmedetomidine.This is a protective factor for sciatic nerve block combined with femoral nerve block in patients undergoing lower limb surgery,and it can be applied clinically.

Background:Duodenal papillary adenoma is a benign tumor with relatively low incidence but significant carcinogenesis potential.Despite the minimal invasiveness and low complication rate,endoscopic papillectomy is associated with a definite risk of recurrence for duodenal papillary adenoma.Investigating the driver genes of duodenal papillary adenoma and establishing predictive models for recurrence and malignant progression could facilitate the precision medicine.Aims:To identify the key driver genes for tumor occurrence,carcinogenesis and recurrence in duodenal papillary adenoma by integrating multi-dimensional bioinformatics approaches based on transcriptomics data,and validate clinically.Methods:Expression profiles of duodenal papillary adenoma and adenocarcinoma were obtained from the GEO database(including data sets GSE189035,GSE94919,GSE111156,and GSE102208).Differentially expressed genes(DEGs)between adenomatous and normal tissues were screened.Weighted gene co-expression network analysis(WGCNA)and pseudo-time analysis were combined to identify the core genes exhibiting an"initial rise followed by decline"expression pattern during the dynamic progression from normal tissue to adenoma and adenocarcinoma.Functional annotation,immune microenvironment profiling,and protein-protein interaction network analysis were performed to explore the tumor-promoting mechanisms of these core genes.Clinical validation was conducted using immunohistochemistry to estimate the gene expression level and its relationship with tumor recurrence.Results:A total of 469 common DEGs were identified.WGCNA revealed that the blue module(including 1 051 genes)was associated with adenoma development and progression(Cor=-0.29,0.15,and 0.11 for normal tissue,adenoma,and adenocarcinoma,respectively).Intersection with DEGs pinpointed four key genes:SLC12A2,BEST4,SLC37A2,and SOAT2.Pseudo-time analysis demonstrated that only SLC12A2 maintained sustained high expression in both adenoma and adenocarcinoma tissues.KEGG enrichment analysis indicated that SLC12A2 was linked to various malignant pathways(e.g.,PD-1/PD-L1 signaling pathway),and its high expression correlated with the reduced immune cell infiltration(e.g.,γδ T cells,CD8+T cells,etc.).Clinical validation by immunohistochemistry confirmed the trend of initial upregulation and subsequent downregulation of SLC12A2 expression in normal,adenoma,and adenocarcinoma tissues.Patients with tumor recurrence showed higher SLC12A2 expression level(P=0.004);likewise,SLC12A2 high expression was associated with an elevated recurrence risk(P=0.034).Conclusions:SLC12A2 serves as a critical driver of tumorigenesis and progression for duodenal papillary adenoma,and might be a promising biomarker for recurrence prediction.

Background:Duodenal papillary adenoma is a benign tumor with relatively low incidence but significant carcinogenesis potential.Despite the minimal invasiveness and low complication rate,endoscopic papillectomy is associated with a definite risk of recurrence for duodenal papillary adenoma.Investigating the driver genes of duodenal papillary adenoma and establishing predictive models for recurrence and malignant progression could facilitate the precision medicine.Aims:To identify the key driver genes for tumor occurrence,carcinogenesis and recurrence in duodenal papillary adenoma by integrating multi-dimensional bioinformatics approaches based on transcriptomics data,and validate clinically.Methods:Expression profiles of duodenal papillary adenoma and adenocarcinoma were obtained from the GEO database(including data sets GSE189035,GSE94919,GSE111156,and GSE102208).Differentially expressed genes(DEGs)between adenomatous and normal tissues were screened.Weighted gene co-expression network analysis(WGCNA)and pseudo-time analysis were combined to identify the core genes exhibiting an"initial rise followed by decline"expression pattern during the dynamic progression from normal tissue to adenoma and adenocarcinoma.Functional annotation,immune microenvironment profiling,and protein-protein interaction network analysis were performed to explore the tumor-promoting mechanisms of these core genes.Clinical validation was conducted using immunohistochemistry to estimate the gene expression level and its relationship with tumor recurrence.Results:A total of 469 common DEGs were identified.WGCNA revealed that the blue module(including 1 051 genes)was associated with adenoma development and progression(Cor=-0.29,0.15,and 0.11 for normal tissue,adenoma,and adenocarcinoma,respectively).Intersection with DEGs pinpointed four key genes:SLC12A2,BEST4,SLC37A2,and SOAT2.Pseudo-time analysis demonstrated that only SLC12A2 maintained sustained high expression in both adenoma and adenocarcinoma tissues.KEGG enrichment analysis indicated that SLC12A2 was linked to various malignant pathways(e.g.,PD-1/PD-L1 signaling pathway),and its high expression correlated with the reduced immune cell infiltration(e.g.,γδ T cells,CD8+T cells,etc.).Clinical validation by immunohistochemistry confirmed the trend of initial upregulation and subsequent downregulation of SLC12A2 expression in normal,adenoma,and adenocarcinoma tissues.Patients with tumor recurrence showed higher SLC12A2 expression level(P=0.004);likewise,SLC12A2 high expression was associated with an elevated recurrence risk(P=0.034).Conclusions:SLC12A2 serves as a critical driver of tumorigenesis and progression for duodenal papillary adenoma,and might be a promising biomarker for recurrence prediction.

Objective To investigate the effect of dexmedetomidine on the median effect concentration(EC50)of ropivacaine during sciatic nerve block combined with femoral nerve block in patients undergoing lower extremity surgery.Methods Patients with sciatic nerve block combined with femoral nerve block anesthesia who underwent lower extremity surgery from November 2021 to November 2023 were selected as the study objects.They were randomly divided into control group(0.9％saline),group D1(0.50 μg·kg-1 dexmedetomidine),group D2(0.75 μg·kg-1 dexmedetomidine)and group D3(1.00 μg·kg-1 dexmedetomidine).The stress response,serum pain mediators,vital signs and visual analogue scale(VAS)of patients at different time points during operation were analyzed by repeated measures ANOVA.ropivacaine EC50 was measured by sequential method,and the relationship between dexmedetomidine dose and ropivacaine EC50 was analyzed by Logistic regression.Results A total of 208 patients were include and each group was 52 patients.Compared with the same group before surgery,the stress response level of the 4 groups after surgery and 1 h after surgery was significantly decreased,and the serum pain mediators level was significantly increased(P＜0.05).Compared with the control group,the stress response and serum pain mediators levels in groups D1,D2 and D3 were more normal after surgery and 1 h after surgery,among them,group D3 was most close to the normal value(P＜0.05).There were no significant differences in blood oxygen saturation and bifrequency index of EEG among the four groups at each time point(P＞0.05).At T1 and T2,the heart rate(HR)of the control group was significantly higher than that of the group D2 and D3(P＜0.05).At T1,the control group had a significantly higher mean arterial pressure(MAP)than the other three groups,at T2,the control group had a significantly higher MAP than the group D2 and D3,and at T3,the control group had a significantly higher MAP than the group D3(P＜0.05).VAS scores in 4 groups were significantly lower after surgery and 1 h after surgery than before surgery(P＜0.05).The VAS score in group D3 was significantly lower than that in group D1 and D2(P＜0.05).Repeated measurement ANOVA showed that the effects of time on stress response and serum pain mediators were different with different anesthesia methods.The influence of time on HR,MAP and VAS scores varied with different anesthesia methods.Sequential assay results showed that the EC50 of ropivacaine in control group,group D1,group D2 and group D3 was 5.985,5.631,5.329 and 5.125 μg·mL-1,respectively.Logistic results showed that the dose of dexmedetomide was a protective factor for ropivacaine EC50 in sciatic nerve block combined with femoral nerve block in limb surgery patients(P＜0.05).Conclusion The ropivacaine EC50 can be significantly reduced by 1.00 μg·kg-1 dexmedetomidine.This is a protective factor for sciatic nerve block combined with femoral nerve block in patients undergoing lower limb surgery,and it can be applied clinically.

Objective To predict the hospitalization expense of pneumonia patients using the CatBoost and LightGBM models and explore associated influencing factors,providing a scientific basis for reasonable control of medical expenses and alle-viating the financial burden on society and patients'families.Methods Data from 1407 inpatients with pneumonia admitted to a tertiary hospital between November 1,2021 and January 31,2023 were collected from the hospital information system.The Cat-Boost and LightGBM models were employed to predict the hospitalization expenses of pneumonia patients and analyze the influen-cing factors.Results The full-variable CatBoost model fitted better than the full-variable LightGBM model,with the R-square value of 0.859 and Mean Absolute Percentage Error(MAPE)of 0.352.The full-variable CatBoost model predicted better than the full-variable LightGBM model,with the R-square value of 0.820 and MAPE of 0.363.Notably,the average length of stay was the most important factor affecting the hospitalization expenses of pneumonia patients.Conclusion Compared to the LightGBM model,the CatBoost model indicated more advantages and higher accuracy in predicting hospitalization expenses for pneumonia patients.These accurate predictions of hospitalization expenses can provide decision-making references for hospital administra-tors.Therefore,on the premise of ensuring medical quality,reasonably reducing the length of hospitalization can effectively con-trol the increase in hospitalization expenses.