Caffeic acid and diabetic neuropathy: Investigating protective effects and insulin-like growth factor 1 (IGF-1)-related antioxidative and anti-inflammatory mechanisms in mice.

Diabetic neuropathy (DN) represents a common and debilitating complication of diabetes, affecting a significant proportion of patients. Despite available treatments focusing on symptom management, there remains an unmet need for therapies that address the underlying pathophysiology. In pursuit of novel interventions, this study evaluated the therapeutic effects of caffeic acid-a natural phenolic compound prevalent in various foods-on diabetic neuropathy using a mouse model, particularly examining its interaction with the Insulin-like Growth Factor 1 (IGF-1) signaling pathway. Caffeic acid was administered orally at two dosages (5 mg/kg and 10 mg/kg), and a comprehensive set of outcomes including fasting blood glucose levels, body weight, sensory behavior, spinal cord oxidative stress markers, inflammatory cytokines, and components of the IGF-1 signaling cascade were assessed. Additionally, to determine the specific contribution of IGF-1 signaling to the observed benefits, IGF1R inhibitor Picropodophyllin (PPP) was co-administered with caffeic acid. Our results demonstrated that caffeic acid, at both dosages, effectively reduced hyperglycemia and alleviated sensory behavioral deficits in diabetic mice. This was accompanied by a marked decrease in oxidative stress markers and an increase in antioxidant enzyme activities within the spinal cord. Significantly lowered microglial activation and inflammatory cytokine expression highlighted the potent antioxidative and anti-inflammatory effects of caffeic acid. Moreover, increases in both serum and spinal levels of IGF-1, along with elevated phosphorylated IGF1R, implicated the IGF-1 signaling pathway as a mediator of caffeic acid's neuroprotective actions. The partial reversal of caffeic acid's benefits by PPP substantiated the pivotal engagement of IGF-1 signaling in mediating its effects. Our findings delineate the capability of caffeic acid to mitigate DN symptoms, particularly through reducing spinal oxidative stress and inflammation, and pinpoint the integral role of IGF-1 signaling in these protective mechanisms. The insights gleaned from this study not only position caffeic acid as a promising dietary adjunct for managing diabetic neuropathy but also highlight the therapeutic potential of targeting spinal IGF-1 signaling as part of a strategic treatment approach.

Application value of MRI-guided wire localization to the non-palpable breast lesions only shown in Breast MRI.

Introduction: Magnetic resonance imaging (MRI)-guided wire localization can be applied to assist to remove suspected breast lesions accurately. This study aimed to evaluate the clinical application value of this technique in Chinese women. Methods: A total of 126 patients (131 lesions) who had underwent such technique in our hospital from April 2017 to June 2023 were enrolled. 1.5T MRI system and a wire localization device were used. Image characteristics, clinical features and postoperative pathology were collected and analyzed. Results: All of 126 patients (131 lesions) were successfully localized by MRI and excised for biopsy. There were 39 malignant lesions (29.77%) and 92 benign lesions (70.23%). There was no significant correlation between the morphology of DCE-MRI and the ratio of malignant lesions (P=0.763), while there was a statistical correlation between the BPE, TIC curve and the malignancy rate (P<0.05). All the lesions were assessed according to BI-RADS category of MRI (C4A=77, C4B=40, C4C=12, C5=2). The malignancy rates were as follows: 16.88% for 4A lesions (13/77), 37.50% for 4B lesions (15/40), 75.00% for 4C lesions (9/12) and 100% for 5 lesions (2/2). There was a significant correlation between the BI-RADS category and the incidence of benign-to-malignant lesions (P<0.001). Conclusion: MRI-guided wire localization can assist to remove suspected breast lesions early, safely and accurately. This technique makes up for the deficiency of X-ray and ultrasound, improves the accuracy of diagnosis and resection therapy in intraductal carcinoma and early invasive carcinoma, and helps to improve the the prognosis of breast cancer.

Implanting Iodine-125 Seed Strand Inside the Portal Vein Stent: An Improved Approach to Endovascular Brachytherapy for Treatment of Patients with Hepatocellular Carcinoma and Main Portal Vein Tumor Thrombus.

Purpose: To investigate the feasibility and efficacy of implanting an iodine-125 (125I) seed strand inside a portal vein stent (PVS) in the treatment of patients with hepatocellular carcinoma (HCC) and main portal vein tumor thrombus (mPVTT). Patients and Methods: Twenty-three patients who diagnosed with HCC and mPVTT and underwent endovascular implantation 125I seed strands and portal vein stenting were included in this study. Patients were divided into two groups. For patients in group A (n = 12), the 125I seed strand was placed outside the PVS, and for those in group B (n = 11), the strand was placed inside the PVS. Technical success, pain intensity during the procedure (numeric rating scale), procedure-related complications, changes in liver function, stent patency, and survival rates were recorded and analyzed. Results: The procedures were successful in all patients, and no serious procedure-related complications occurred in either group. Pain intensity during the procedure was significantly lower in group B than in group A (2.64 ± 1.50 vs 4.08 ± 1.78, p = 0.048), and there were no significant differences between pre- and post-procedure liver function in either group. The median duration of stent patency was 9 months (95% CI 2.21-15.79 months) in group A and 12 months (95% CI 3.63-18.37 months) in group B (p = 0.670). Median survival was 12 months (95% CI 10.30-13.70 months) in group A and 13 months (95% CI 10.03-15.97 months) in group B (p = 0.822). The cumulative stent patency and survival rates at 3, 6, and 12 months were 75%, 50%, and 41.7%, and 83.3%, 75%, and 50% in group A and 72.7%, 62.3%, and 31.2%, and 90.9%, 80.8%, and 50.5%, respectively. Conclusion: Implantation of 125I seed strand inside the PVS is effective and feasible for treating patients with HCC and mPVTT.

Targeted RASSF1A expression inhibits proliferation of HER2­positive breast cancer cells in vitro.

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer, which accounts for 15-20% of all breast cancer, is associated with tumor recurrence and poor prognosis. RAS association domain family protein 1 subtype A (RASSF1A) is a tumor suppressor that is silenced in a variety of human cancers. The present study aimed to investigate the role of RASSF1A in HER2+ breast cancer and the therapeutic potential of RASSF1A-based targeted gene therapy for this malignancy. RASSF1A expression in human HER2+ breast cancer tissues and cell lines was evaluated by reverse transcription PCR and western blot analysis. The associations between tumorous RASSF1A level and tumor grade, TNM stage, tumor size, lymph node metastasis and five-year survival were examined. HER2+ and HER2-negative (HER2-) breast cancer cells were transfected with a lentiviral vector (LV-5HH-RASSF1A) that could express RASSF1A under the control of five copies of the hypoxia-responsive element (5HRE) and one copy of the HER2 promoter (HER2p). Cell proliferation was evaluated by the MTT and colony formation assays. It was found that tumorous RASSF1A level was negatively associated with tumor grade (P=0.014), TNM stage (P=0.0056), tumor size (P=0.014) and lymph node metastasis (P=0.029) and positively associated with five-year survival (P=0.038) in HER2+ breast cancer patients. Lentiviral transfection of HER2+ breast cancer cells resulted in increased RASSF1A expression and decreased cell proliferation, especially under hypoxic conditions. However, lentiviral transfection of HER2-breast cancer cells did not affect RASSF1A expression. In conclusion, these findings verified the clinical significance of RASSF1A as a tumor suppressor in HER2+ breast cancer and supported LV-5HH-RASSF1A as a potential targeted gene therapy for this malignancy.

Serum hsa_circ_0054633 Is Elevated and Correlated with Clinical Features in Type 2 Diabetes Mellitus.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a chronic disease that seriously threatens human health with high incidence and various complications. Circular RNA has become a research hotspot in recent years due to its high stability and wide expression, and has been found to be related to many diseases. The main purpose of this study was to investigate the expression of serum hsa_circ_0054633 in T2DM patients and explore the potential role of serum hsa_circ_0054633 in T2DM diagnosis and its association with clinical characteristics. METHODS: This retrospective case-control study enrolled 88 participants including 44 patients with T2DM and 44 age- and sex-matched controls between January 2018 and March 2019 at Ningxia Medical University General Hospital. Serum hsa_circ_0054633 levels were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) with absolute quantification. Baseline information including clinical background, glucose control and biochemical variables were collected. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic effect. RESULTS: We found that serum expression of hsa_circ_0054633 was dramatically increased in patients with T2DM. Serum hsa_circ_0054633 levels had high sensitivity (75.0%) and specificity (95.5%) for differentiating T2DM. Besides, serum expression of circ_0054633 was significantly correlated with fasting blood glucose (r=0.698), hemoglobin A1c (r=0.503) and low-density lipoprotein (r=0.399). CONCLUSION: Serum hsa_circ_0054633 is a potential noninvasive biomarker in discerning T2DM and is associated with changes in blood glucose and lipid.

Effect of pre-emptive analgesia by continuous femoral nerve block on early postoperative cognitive function following total knee arthroplasty in elderly patients.

To the best of our knowledge, the effect of pre-emptively blocking pain transmission on acute postoperative cognitive dysfunction (POCD) has not yet been assessed. Therefore, the present study aimed to investigate the effect of pre-emptive analgesia via a continuous femoral nerve block (CFNB) on postoperative pain and early cognitive function following total knee arthroplasty (TKA) surgery in elderly patients. CFNB was performed prior to TKA surgery in the pre-emptive analgesia group (n=30) and following TKA surgery in the control group (n=30). POCD was defined as a two-point reduction in the postoperative score compared with the preoperative score in the mini-mental state examination. The visual analog scale (VAS) was used to evaluate the intensity of pain at rest and during exercise. The intraoperative dose of remifentanil in the pre-emptive analgesia group was significantly lower than in the control group (P<0.01). In the preemptive analgesia group, VAS scores at three days post-surgery were lower than those in the control group (P<0.01). The incidence of POCD on the third postoperative day was slightly lower in the pre-emptive analgesia group compared with the control group. In conclusion, the results demonstrate that pre-emptive analgesia by CFNB may promote the recovery of early cognitive function following TKA in elderly patients.