ObjectiveTo clarify the associations between plasma fibrinogen （Fbg） and volumetric bone mineral density （vBMD） as well as osteoporosis measured by quantitative computed tomography （QCT）， and to explore the role of plasma Fbg in early screening and diagnosis of osteoporosis. MethodsPatients with hypertension who were hospitalized in the Department of Endocrinology of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to June 2022 and underwent QCT examinations were included for cross-sectional analysis. The study analyzed the correlation between plasma Fbg and osteoporosis in patients. The diagnostic efficacy of plasma Fbg for osteoporosis was evaluated by the area under the receiver operating characteristic （ROC） curve （AUC）. ResultsTotally 441 subjects were included in the analysis， with an average age of 46.0±14.5 years and a prevalence of osteoporosis of 6.4% （28/441）. As the level of plasma fibrinogen increased， the incidence of osteoporosis significantly increased （P<0.000 1）while the average bone mineral density of L1 and L2 were significantly decreased （P<0.05）. Compared with the first quartile of plasma Fbg（1.99g/L -2.37g/L）， the risk of osteoporosis in the fourth quartile of plasma Fbg （3.67g/L-4.46g/L） increased by 8.85 times after adjusting for related confounding factors. ConclusionThis study found a negative correlation between plasma fibrinogen levels and bone density in patients with hypertension. Plasma fibrinogen levels may serve as a potential screening indicator for osteoporosis， aiding in early diagnosis and therapeutic monitoring. This discovery offers a new perspective for the study of bone metabolic diseases and warrants further investigation.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

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.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

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.

OBJECTIVE: To investigate the potential mechanism by which electroacupuncture (EA) induces macrophage polarization to promote muscle satellite cell proliferation and differentiation, accelerating the repair of acute skeletal muscle injury. METHODS: Forty-two SPF-grade SD rats were randomly divided into three groups: a blank group (n=6), a model group (n=18), and an EA group (n=18). The model and EA groups established acute blunt contusion model of the right gastrocnemius muscle using a self-made striking device. From day 1 after modeling, rats in the EA group received EA at "Chengshan" (BL57) and "Yanglingquan" (GB34) on the right side, using disperse-dense wave with a frequency of 2 Hz/100 Hz and a current of approximately 2 mA. The EA treatment was administered once daily for 30 minutes for 3, 7, or 14 days based on the designated sampling time points. Gait analysis was performed using the Cat Walk XT^TM system. Hematoxylin-eosin (HE) staining was used to observe the morphological changes in the gastrocnemius muscle. Masson staining was applied to evaluate collagen fiber content. Immunofluorescence was used to detect the expression of proliferating cell nuclear antigen (PCNA) in muscle satellite cells. Immunohistochemistry was used to assess the expression levels of CD68 and CD206, markers of macrophages. Serum levels of pro-inflammatory cytokines (TNF-α, IL-1β) and anti-inflammatory cytokines (IL-10, IL-13) were detected using ELISA. RESULTS: Compared with the blank group, the model group showed a significant reduction in average movement speed on days 3 and 7 after modeling (P<0.05), and a decrease in the right hind limb stride length on day 3 (P<0.05). Compared with the model group, the EA group showed increased average movement speed and right hind limb stride length on day 7 (P<0.05). In the blank group, the gastrocnemius muscle on the right side showed uniform and consistent inter-fiber spacing, with neatly and regularly arranged muscle cells. In contrast, the model group exhibited enlarged inter-fiber spacing, edema, and significant infiltration of red blood cells and inflammatory cells, with progressively increasing fibrosis over time. By day 14 after modeling, the EA group showed a return to baseline levels of inflammatory cell infiltration, and the degree of fibrosis was significantly lower than that observed in the model group. Compared with the blank group, the ratio of collagen fibers in the gastrocnemius muscle of the model group increased significantly on days 3, 7, and 14 after modeling (P<0.05). Compared with the model group, the EA group exhibited a lower collagen fiber ratio on days 3, 7, and 14 (P<0.05). Compared with the blank group, PCNA positive expression in the gastrocnemius muscle of the model group was significantly increased on days 3, 7, and 14 after modeling (P<0.05). Compared with the model group, the EA group exhibited significantly higher PCNA positive expression on days 3 and 7 (P<0.05). Compared with the blank group, the model group showed a significant increase in CD68-positive macrophage expression in the gastrocnemius muscle on day 3 after modeling (P<0.05), while CD206-positive macrophage expression increased on days 3, 7, and 14 (P<0.05). Compared with the model group, CD68 expression was significantly lower in the EA group on day 3 (P<0.05), whereas CD206 expression was significantly higher on days 3 and 7 (P<0.05), peaking on day 7 with CD206 expression. Compared with the blank group, serum TNF-α levels were significantly elevated in the model group on days 3 and 7 after modeling (P<0.05), while serum IL-1β levels were increased on days 3, 7, and 14 (P<0.05). Serum IL-10 and IL-13 levels were significantly higher on day 7 after modeling (P<0.05). Compared with the model group, the EA group exhibited lower serum TNF-α level on day 3 (P<0.05) and reduced serum IL-1β levels on days 3 and 7 (P<0.05), while serum IL-10 and IL-13 levels were significantly increased on day 7 (P<0.05). CONCLUSION EA could promote the repair of acute blunt contusion-induced gastrocnemius muscle injury by regulating the proliferation and differentiation of muscle satellite cells. This process is closely related to macrophage polarization.
Animals ; Electroacupuncture ; Rats, Sprague-Dawley ; Rats ; Macrophages/immunology* ; Muscle, Skeletal/immunology* ; Male ; Humans ; Female ; Tumor Necrosis Factor-alpha/immunology* ; Cell Proliferation

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*