Efficacy and safety of radiofrequency ablation versus surgical sympathectomy in palmar hyperhidrosis.

Radiofrequency ablation (RFA) comparative efficacy of treatments using video-assisted thoracoscopic sympathectomy (VATS) in the long term remains uncertain in patients with palmar hyperhidrosis (PHH). This study aimed to compare the efficacy and safety of RFA and VATS in patients with PHH. We recruited patients aged ≥ 14 years with diagnosed PHH from 14 centres in China. The treatment options of RFA or VATS were assigned to two cohort in patients with PHH. The primary outcome was the efficacy at 1-year. A total of 807 patients were enrolled. After propensity score matching, the rate of complete remission was lower in RFA group than VATS group (95% CI 0.21-0.57; p < 0.001). However, the rates of palmar dryness (95% CI 0.38-0.92; p = 0.020), postoperative pain (95% CI 0.13-0.33; p < 0.001), and surgery-related complications (95% CI 0.19-0.85; p = 0.020) were lower in RFA group than in VATS group, but skin temperature rise was more common in RFA group (95% CI 1.84-3.58; p < 0.001). RFA had a lower success rate than VATS for the complete remission of PHH. However, the symptom burden and cost are lower in patients undergoing RFA compared to those undergoing VATS.Trial Registration: ChiCTR2000039576, URL: http://www.chictr.org.cn/index.aspx .

YBX1 Promotes MSC Osteogenic Differentiation by Activating the PI3K/AKT Pathway.

INTRODUCTION: Bone metabolism has an essential role in bone disease, but its specific mechanism remains unclear. Y-Box Binding Protein 1 (YBX1) is a gene with broad nucleic acid binding properties, which encodes a highly conserved cold shock domain protein. Previous studies have shown that YBX1 is closely related to cell differentiation. However, the function of YBX1 in osteoblast differentiation of bone marrow mesenchymal stem cells (MSCs) was unclear. METHODS: To explore the effect and specific mechanism of YBX1 in osteogenic differentiation of MSCs, we used PCR, Western blot, Alizarin red Staining, alkaline phosphatase (ALP) assays, and siRNA knockdown in our research. We found that YBX1 gradually increased during the process of osteogenic differentiation of MSCs. YBX1 siRNA could negatively regulate the MSCs osteogenic differentiation. Mechanistic studies revealed that YBX1 knockdown could inhibit PI3K/AKT pathway. Furthermore, the specific agonist (SC79) of PI3K/AKT pathway could restore the impaired MSCs osteogenic differentiation which was mediated by YBX1 knockdown. Taken together, we concluded that YBX1 could positively regulate the osteogenic differentiation of MSCs by activating the PI3K/AKT pathway. RESULTS AND DISCUSSION: These results helped us further understand the mechanism of osteogenesis and revealed that YBX1 might be a selectable target in the bone repair field. CONCLUSION: Our study provides a new target and theoretical basis for the treatment of bone diseases.

The impact of CRMP4 SUMOylation on the Cav1.2 interaction, neurite outgrowth and thermal pain sensitivity.

Collapsin response mediator protein 4 (CRMP4) is critical for neuronal development. However, whether CRMP4 could be SUMOylated and how the SUMOylation regulates the interaction with the L-type voltage-gated calcium channel (Cav1.2), neurite outgrowth, and thermal pain sensitivity remain to be elucidated. To determine the SUMOylation of CRMP4, Glutathione S-transferase (GST) - Small Ubiquitin-like Modifier 1 (-SUMO1), -SUMO2, and -SUMO3 proteins were purified for GST-pulldown. Immunofluorescence staining was performed to observe colocalization of CRMP4 and SUMOs. Co-immunoprecipitation (co-IP) was performed to assess the interaction between CRMP4 and SUMO2. GST-pulldown and co-IP were performed to verify the interaction between CRMP4 and Cav1.2. The impact of SUMOylation of CRMP4 on its interaction with Cav1.2 was determined. Then, the effect of CRMP4 SUMOylation on neurite outgrowth was observed. Whole-cell patch clamping revealed the effect of CRMP4 SUMOylation on Cav1.2 mediated calcium influx. Paw withdrawal latency was measured to assess the impact of CRMP4 SUMOylation on thermal pain sensitivity in rats. The data revealed that CRMP4 K374 is a potential site for SUMO modification. SUMO1, SUMO2, and SUMO3 can all interact with CRMP4. SUMO2 interacts with CRMP4, but not a variant of CRMP4 harboring a mutation of K374. CRMP4 and SUMO proteins colocalized in neurites, and CRMP4 deSUMOylation promoted neurite outgrowth. CRMP4 interacted with Cav1.2, and deSUMOylation of CRMP4 strengthened this interaction. CRMP4 promoted calcium influx via Cav1.2, and overexpression of CRMP4 significantly increased thermal pain sensitivity in rats, which CRMP4 deSUMOylation strengthened. In conclusion, these data demonstrate the SUMOylation of CRMP4, elucidate the impacts of SUMOylation on the interaction with Cav1.2 on neurite outgrowth and thermal pain sensitivity.