Purpose: To investigate the therapeutic potential of eliminating insulin-like growth factor-binding protein 5 (IGFBP5) expression in improving erectile function in mice with cavernous nerve injury (CNI)-induced erectile dysfunction (ED). Materials and Methods: Eight-week-old male C57BL/6 mice were divided into four groups: a sham-operated group and three CNI-induced ED groups. The CNI-induced ED groups were treated with intracavernous injections 3 days before the CNI procedure.These injections included phosphate-buffered saline, scrambled control short hairpin RNA (shRNA), or shRNA targeting mouse IGFBP5 lentiviral particles. One week after CNI, erectile function was evaluated and the penile tissue was then harvested for histological examination and western blot analysis. Additionally, the major pelvic ganglia (MPG) and dorsal root ganglia (DRG) were cultured for ex vivo neurite outgrowth assays. Results: Following CNI, IGFBP5 expression in the cavernous tissues significantly increased, reaching its peak at day 7. First, ablation of IGFBP5 expression promotes neurite sprouting in MPG and DRG when exposed to lipopolysaccharide. Second, ablating IGFBP5 expression in CNI-induced ED mice improved erectile function, likely owing to increased neurovascular contents, including endothelial cells, pericytes, and neuronal processes. Third, ablating IGFBP5 expression in CNI-induced ED mice promoted neurovascular regeneration by increasing cell proliferation, reducing apoptosis, and decreasing Reactive oxygen species production. Finally, western blot analysis demonstrated that IGFBP5 ablation attenuated the JNK/c-Jun signaling pathway, activated the PI3K/AKT signaling pathway, and increased vascular endothelial growth factor and neurotrophic factor expression. Conclusions Ablating IGFBP5 expression enhanced neurovascular regeneration and ultimately improved erectile function in CNI-induced ED mice.

Objective To understand the disease spectrum of a natural village in an area with high incidence of esophageal cancer to provide a reference for precise prevention and control. Methods From 2008 to 2024, 711 asymptomatic people over the age of 35 years in a natural village with high incidence of esophageal cancer in China were surveyed, and 171 of them were subjected to gastroscopy, biopsy, and pathological examination. All participants were followed up for a long time, and their disease history was recorded. Results A total of 16 years of follow-up were performed, and 703 people were effectively followed up. In 2008, 171 people underwent gastroscopy, and 160 people had biopsy and pathological results in endoscopic screening. By 2024, 76 people had been diagnosed with malignant tumors of 12 different types, and among these people, 45 had esophageal cancer. Conclusion Esophageal cancer remains a significant cause of morbidity and mortality from malignant tumors in this region. Biopsy and pathological examination should be strengthened during gastroscopy, and follow-ups and regular check-ups should be given high importance to reduce the incidence and mortality rates of esophageal cancer.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Pericytes are multifunctional mural cells that surround the abluminal wall of endothelial cells and are associated with vascular development, vascular permeability, and angiogenesis. Additionally, pericytes demonstrate stem cell-like properties and contribute to neuroinflammatory processes. Pericytes have been extensively studied in the central nervous system. However, specific mechanisms underlying its involvement in various physiological and pathological conditions, especially in erectile dysfunction (ED), remain poorly understood. Advancements in in vitro and in vitro techniques, such as single-cell RNA sequencing, are expanding our understanding of pericytes. Recent studies have shown that pericyte dysfunction is considered an important factor in the pathogenesis of vascular and neurological ED. Therefore, this study aims to analyze the specific role of pericytes in ED, focusing on diabetic and neurogenic ED. This article provides a comprehensive review of research findings on PubMed from 2000 to 2023, concerning pericyte dysfunction in the process of ED, offering valuable insights, and suggesting directions for further research.
Pericytes/physiology* ; Humans ; Male ; Penis/innervation* ; Erectile Dysfunction/physiopathology* ; Nerve Regeneration/physiology* ; Neovascularization, Physiologic/physiology* ; Animals ; Angiogenesis

Prostate cancer is the second most common malignancy and the sixth leading cause of cancer-related death in men worldwide. Radical prostatectomy (RP) is the standard treatment for localized prostate cancer, but the procedure often results in postoperative erectile dysfunction (ED). The poor efficacy of phosphodiesterase 5 inhibitors after surgery highlights the need to develop new therapies to enhance cavernous nerve regeneration and improve the erectile function of these patients. In the present study, we aimed to examine the potential of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in preserving erectile function in cavernous nerve injury (CNI) mice. We found that HB-EGF expression was reduced significantly on the 1 st day after CNI in penile tissue. Ex vivo and in vitro studies showed that HB-EGF promotes major pelvic ganglion neurite sprouting and neuro-2a (N2a) cell migration. In vivo studies showed that exogenous HB-EGF treatment significantly restored the erectile function of CNI mice to 86.9% of sham levels. Immunofluorescence staining showed that mural and neuronal cells were preserved by inducing cell proliferation and reducing apoptosis and reactive oxygen species production. Western blot analysis showed that HB-EGF upregulated protein kinase B and extracellular signal-regulated kinase activation and neurotrophic factor expression. Overall, HB-EGF is a major promising therapeutic agent for treating ED in postoperative RP.
Animals ; Male ; Heparin-binding EGF-like Growth Factor/therapeutic use* ; Erectile Dysfunction/etiology* ; Mice ; Penis/drug effects* ; Nerve Regeneration/drug effects* ; Penile Erection/drug effects* ; Peripheral Nerve Injuries/drug therapy* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Prostatectomy/adverse effects* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism*

OBJECTIVE: To investigate lymph node metastasis (LNM) in the prostatic anterior fat pad (PAFP) of PCa patients after robot-assisted radical prostatectomy (RARP), and analyze the clinicopathological features and prognosis of LNM in the PAFP. METHODS: We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urology of PLA General Hospital from January 2017 to December 2022. All the patients underwent routine removal of the PAFP during RARP and pathological examination, with the results of all the specimens examined and reported by pathologists. Based on the presence and locations of LNM, we grouped the patients for statistical analysis, compared the clinicopathological features between different groups using the Student's t, Mann-Whitney U and Chi-square tests, and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio. RESULTS: Lymph nodes were detected in 77 (7.7%) of the 1 003 PAFP samples, and LNM in 11 (14.3%) of the 77 cases, with a positive rate of 1.1% (11/1 003). Of the 11 positive cases, 9 were found in the upgraded pathological N stage, and the other 2 complicated by pelvic LNM. The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group (81.8% ［9/11］ vs 36.2% ［359/992］, P = 0.005), and so did the cases with Gleason score ≥8 (87.5% ［7/8］ vs 35.5% ［279/786］, P = 0.009). No statistically significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the patients with PAFP LNM only and those with pelvic LNM only. CONCLUSION The PAFP is a potential route to LNM, and patients with LNM in the PAFP are characterized by poor pathological features. There is no statistically significant difference in biochemical recurrence-free survival between the patients with PAFP LNM only and those with pelvic LNM only. Routine removal of the PAFP and independent pathological examination of the specimen during RARP is of great clinical significance.
Humans ; Male ; Prostatectomy/methods* ; Robotic Surgical Procedures ; Lymphatic Metastasis ; Retrospective Studies ; Prognosis ; Prostatic Neoplasms/pathology* ; Adipose Tissue/pathology* ; Prostate/pathology* ; Lymph Nodes/pathology* ; Middle Aged ; Aged

Purpose: To identify the optimal photobiomodulation (PBM) parameters using molecular, histological, and erectile function analysis in cavernous nerve injury. Materials and Methods: A cavernous nerve injury was induced in 8-week-old C57BL/6J male mice that were subsequently divided randomly into age-matched control groups. Erectile function tests, penile histology, and Western blotting were performed 2 weeks after surgery and PBM treatment. Results: The PBM treatment was administered for five consecutive days with a light-emitted diode (LED) device that delivers 660 nm±3% RED light, and near infra-red 830 nm±2% promptly administered following nerve-crushing surgery and achieved a notable restoration of erectile function approximately 90% of the control values. Subsequent in-vitro and ex-vivo analyses revealed the regeneration of neurovascular connections in both the dorsal root ganglion and major pelvic ganglion, characterized by the sprouting of neurites. Furthermore, the expression levels of neurotrophic, survival, and angiogenic factors exhibited a substantial increase across all groups subjected to PBM treatment. Conclusions The utilization of PBM employing LED with 660 nm, 830 nm, and combination of both these wavelengths, exhibited significant efficacy to restore erectile function in a murine model of cavernous nerve injury. Thus, the PBM emerges as a potent therapeutic modality with notable advantages such as efficacy, noninvasiveness, and non-pharmacological interventions for erectile dysfunction caused by nerve injury.

BACKGROUND:Hypoxia is strongly associated with the development and progression of osteoarthritic chondrocyte injury,but the specific targets and regulatory mechanisms are unclear. OBJECTIVE:A machine learning approach was used to identify KDEL(Lys-Asp-Glu-Leu)receptor 3(KDELR3)as a characteristic gene for osteoarthritis hypoxia and immune infiltration analysis,to provide new ideas and methods for the treatment of osteoarthritis. METHODS:The osteoarthritis-related datasets were downloaded from the GEO database and the GSEA website to obtain hypoxia-related genes.The osteoarthritis datasets were batch-corrected and immune infiltration analyzed using R language,and osteoarthritis hypoxia genes were extracted for differential analysis.Differentially expressed genes were analyzed for GO function and KEGG signaling pathway.Weighted correlation network analysis(WGCNA)and machine learning were also used to screen osteoarthritis hypoxia signature genes,and in vitro cellular experiments were performed to validate expression and correlate immune infiltration analysis using the datasets and qPCR. RESULTS AND CONCLUSION:(1)8492 osteoarthritis genes were obtained by batch correction and principal component analysis,mainly strongly associated with immune cells such as Macrophages M2 and Mast cells resting;200 hypoxia genes were also obtained,resulting in 41 osteoarthritis hypoxia differentially expressed genes.(2)GO analysis involved mainly biological processes such as response to nutrient levels and glucocorticoids;cellular components such as lysosomal lumen and Golgi lumen;and molecular functions such as 14-3-3 protein binding and DNA-binding transcriptional activator activity.(3)KEGG analysis of osteoarthritis hypoxia differentially expressed genes was associated with signaling pathways such as PI3K-Akt,FoxO,and microRNAs in cancer.(4)The characteristic gene KDELR3 was obtained after using WGCNA analysis and machine learning screening.(5)The gene expression of KDELR3 was found to be higher in the test group than in the control group in the synovium(P=0.014)but lower in the meniscus(P=0.024)after validation by gene microarray.(6)In vitro chondrocyte assay showed that the expression of KDELR3 was higher in cartilage than in the control group(P=0.005),while KDELR3 was closely associated with Macrophages M0(P=0.014)and T cells follicular helper(P=0.014).Using a machine learning approach,we confirmed that KDELR3 can be used as a hypoxic signature gene for osteoarthritis and may intervene in osteoarthritis pathogenesis by improving hypoxia,expecting to provide a new direction for better treatment of osteoarthritis.

BACKGROUND:Ferroptosis is strongly associated with the occurrence and progression of osteoarthritis,but the specific characteristic genes and regulatory mechanisms are not known. OBJECTIVE:To identify osteoarthritis ferroptosis signature genes and immune infiltration analysis using the WGCNA and various machine learning methods. METHODS:The osteoarthritis dataset was downloaded from the GEO database and ferroptosis-related genes were obtained from the FerrDb website.R language was used to batch correct the osteoarthritis dataset,extract osteoarthritis ferroptosis genes and perform differential analysis,analyze differentially expressed genes for GO function and KEGG signaling pathway.WGCNA analysis and machine learning(random forest,LASSO regression,and SVM-RFE analysis)were also used to screen osteoarthritis ferroptosis signature genes.The in vitro cell experiments were performed to divide chondrocytes into normal and osteoarthritis model groups.The dataset and qPCR were used to verify expression and correlate immune infiltration analysis. RESULTS AND CONCLUSION:(1)12 548 osteoarthritis genes were obtained by batch correction and PCA analysis,while 484 ferroptosis genes were obtained,resulting in 24 differentially expressed genes of osteoarthritis ferroptosis.(2)GO analysis mainly involved biological processes such as response to oxidative stress and response to organophosphorus,cellular components such as apical and apical plasma membranes,and molecular functions such as heme binding and tetrapyrrole binding.(3)KEGG analysis exhibited that differentially expressed genes of osteoarthritis ferroptosis were related to signaling pathways such as the interleukin 17 signaling pathway and tumor necrosis factor signaling pathway.(4)After using WGCNA analysis and machine learning screening,we obtained the characteristic gene KLF2.After validation by gene microarray,we found that the gene expression of KLF2 was higher in the test group than in the control group in the meniscus(P=0.000 14).(5)In vitro chondrocyte assay showed that type Ⅱ collagen and KLF2 expression was lower in the osteoarthritis group than in the control group in chondrocytes(P<0.05),while in osteoarthritis ferroptosis,mast cells activated was closely correlated with dendritic cells(r=0.99);KLF2 was closely correlated with natural killer cells(r=-1,P=0.017)and T cells follicular helper(r=-1,P=0.017).(6)The findings indicate that using WGCNA analysis and machine learning methods confirmed that KLF2 can be a characteristic gene for osteoarthritis ferroptosis and may improve osteoarthritis ferroptosis by interfering with KLF2.

Objective To investigate the balance control abilities and cortical activation characteristics of elderly individuals under different sensory strategies. Methods From January to May,2023,19 healthy young adults and 20 elderly individuals were recruited in Changzhou as control group and experimental group,respectively.Both groups wore functional near-infrared spectroscopy(fNIRS)caps and performed balance control tasks on a balance platform under three different sensory strategies.Test A was 40 seconds of standing on a stable surface with eyes closed,Test B was 40 seconds of standing on an unstable surface with eyes open,and Test C was 40 seconds of standing on an unstable surface with eyes closed.Before and after the tests,both groups performed 40 seconds of standing on a stable surface with eyes open.The overall stability index(OSI)and cortical activation β values of the regions of interest(ROI)were measured and compared between two groups.The ROIs included the left premotor cortex(LPMC),right premotor cortex(RPMC),left sensorimotor cortex(LSMC),right sensorimotor cortex(RSMC),left prefrontal cortex(LPFC)and right prefrontal cortex(RPFC). Results There was no significant difference in OSI and β values of each ROI in Tests A and B between two groups(P>0.05).In Test C,there was a lower OSI in the experimental group(Z=-2.056,P<0.05),and there were signifi-cant differences in the β values of RSMC(t=2.623,PFDR<0.05),LPMC(Z=-2.360,PFDR<0.05)and LPFC(t=3.202,PFDR<0.05)between two groups. Conclusion Elderly individuals experience a decline in balance control abilities,accompanied by increased activation in related brain regions,when both vision and proprioception are restricted.