BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Objective To explore the intrinsic relationship between imaging features of the bony structure in varus-type knee osteoarthritis(KOA).Methods A total of 99 patients diagnosed with varus-type KOA were retrospectively selected.All patients underwent standard weight-bearing full-length X-ray radiographs of both lower extremities and 3D CT scans of the knee joints.The images were observed and analyzed at the picture archiving and communication system(PACS)workstation.The hip-knee-ankle(HKA)angle and tibial medial plateau settlement value were measured,the size of osteophyte was measured and graded,and the distribution of subchondral pseudocysts was counted.Correlation analysis was performed on the above imaging indicators,and scatter plots were drawn for linear correlations.Results There was a correlation between the HKA angle and the tibial medial plateau settlement value,with a correlation coefficient(r)of-0.548.The osteophyte grades in each subregion were correlated with the HKA angle,with r of-0.324,-0.307,-0.534,-0.581,-0.468,-0.245,-0.265,-0.244,-0.706,-0.741,-0.726,-0.326,-0.712,-0.218,respectively.There was correlation between the osteophyte grades in the medial patella,medial femoral subregion,and medial tibial subregion and the tibial medial settlement value,with r of 0.227,0.263,0.295,0.242,0.297,0.361,and 0.407,respectively.No correlation was found between the osteophyte grades in other subregions and the tibial medial settlement value.There was an overall correlation between osteophyte grades and subchondral pseudocysts,with a r of 0.245,but with regional differences.No correlation was found between the medial femoral osteophyte grades and subchondral pseudocysts,while correlations were observed in other zones,with r of 0.213,0.230,0.200,and 0.147,respectively.Conclusion KOA is a disease of the entire knee joint.The imaging features of its bony structure,including the HKA angle,tibial medial plateau settlement value,osteophyte grades,and subchondral pseudocysts,have both intrinsic relationship and regional differences,which are influenced by anatomical structures.

Objective To explore the intrinsic relationship between imaging features of the bony structure in varus-type knee osteoarthritis(KOA).Methods A total of 99 patients diagnosed with varus-type KOA were retrospectively selected.All patients underwent standard weight-bearing full-length X-ray radiographs of both lower extremities and 3D CT scans of the knee joints.The images were observed and analyzed at the picture archiving and communication system(PACS)workstation.The hip-knee-ankle(HKA)angle and tibial medial plateau settlement value were measured,the size of osteophyte was measured and graded,and the distribution of subchondral pseudocysts was counted.Correlation analysis was performed on the above imaging indicators,and scatter plots were drawn for linear correlations.Results There was a correlation between the HKA angle and the tibial medial plateau settlement value,with a correlation coefficient(r)of-0.548.The osteophyte grades in each subregion were correlated with the HKA angle,with r of-0.324,-0.307,-0.534,-0.581,-0.468,-0.245,-0.265,-0.244,-0.706,-0.741,-0.726,-0.326,-0.712,-0.218,respectively.There was correlation between the osteophyte grades in the medial patella,medial femoral subregion,and medial tibial subregion and the tibial medial settlement value,with r of 0.227,0.263,0.295,0.242,0.297,0.361,and 0.407,respectively.No correlation was found between the osteophyte grades in other subregions and the tibial medial settlement value.There was an overall correlation between osteophyte grades and subchondral pseudocysts,with a r of 0.245,but with regional differences.No correlation was found between the medial femoral osteophyte grades and subchondral pseudocysts,while correlations were observed in other zones,with r of 0.213,0.230,0.200,and 0.147,respectively.Conclusion KOA is a disease of the entire knee joint.The imaging features of its bony structure,including the HKA angle,tibial medial plateau settlement value,osteophyte grades,and subchondral pseudocysts,have both intrinsic relationship and regional differences,which are influenced by anatomical structures.

Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Objective To investigate the predictive value of combining MRI with full-length X-ray of both lower extremities in grading varus knee osteoarthritis(KOA).Methods A retrospective analysis was conducted on 176 patients diagnosed with varus KOA.All patients underwent X-ray K-L grading.Correlation analysis was performed between K-L grading and variables such as gen-der,age,side,meniscus grading,hip knee ankle(HKA)angle,meniscus peripheral displacement,medial osteochondral injury grad-ing,and medial bone marrow edema(BME)score.Varus KOA was converted into a binary classification variable of mild and severe osteoarthritis.Statistically significant variables were introduced into univariate and multivariate logistic regression models for analysis to screen out predictive factors for varus KOA grading.Diagnostic efficacy evaluation of predictive factors was further conducted using receiver operating characteristic(ROC)curves and other statistical methods.Results K-L grading was correlated with age,HKA angle,meniscus grading,meniscus peripheral displacement,medial osteochondral injury grading,and medial BME score,with r of 0.344,-0.584,0.369,0.443,0.586,and 0.616,respectively.Through univariate and multivariate logistic regression models,three predictive factors were finally selected:meniscus peripheral displacement,medial BME score,and HKA angle,with odds ratio(OR)values of 1.374,1.258,and 0.772,respectively.The area under the curve(AUC)of ROC curves were 0.736,0.804,and 0.799,with 95％confidence interval(CI)of 0.662-0.810,0.740-0.867,and 0.731-0.868,respectively.At cut-off values of 3.5 mm,5.5 and 174.5°,the sensitivity were 64.0％,62.3％,and 80.7％,the specificity were 80.6％,83.9％,and 66.1％,and the accuracy were 70.0％,70.0％,and 75.6％,respectively.Conclusion The three imaging indications of medial BME score,HKA angle,and meniscus periph-eral displacement can provide preliminary predictions for mild and severe grading of varus KO A,offering valuable references for clini-cal treatment selection.