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We studied an amorphous solid dispersion of berberine with absorption enhancer sodium caprate (Huang-Gui solid dispersion preparations, HGSD). A therapeutic effect of HGSD was revealed in mice with type 2 diabetes mellitus and palmitate-induced injury to MIN6 β-cells. HGSD treatment (150 mg/kg) improved glucose metabolism and decreased β-cell apoptosis in diabetic mice. Furthermore, the effective component of HGSD berberine significantly attenuated the palmitate-induced decrease in MIN6 β-cells viability and insulin secretion. Moreover, molecular docking analysis and Western blotting showed that berberine decreased cell apoptosis and expression of group VIA phospholipase A 2 (iPLA 2 ), p38 mitogen-activated protein kinase (p38 MAPK), and caspase-3. These data suggest that HGSD treatment protected β-cells via inhibiting the iPLA 2 /p38 MAPK pathway., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Rheumatoid arthritis (RA) is an autoimmune disease, which attacks human joint system and causes lifelong inflammatory condition. To date, no cure is available for RA and even the ratio of achieving remission is very low. Hence, to enhance the efficacy of RA treatment, it is essential to develop novel approaches specifically targeting pathological tissues. In this study, we discovered that RA synovial fibroblasts exhibited higher reactive oxygen species (ROS) and mitochondrial superoxide level, which were adopted to develop ROS-responsive nano-medicines in inflammatory microenvironment for enhanced RA treatment. A selenocystamine-based polymer was synthesized as a ROS-responsive carrier nanoplatform, and berberine serves as a tool drug. By assembling, ROS-responsive berberine polymeric micelles were fabricated, which remarkably increased the uptake of berberine in RA fibroblast and improved in vitro and in vivo efficacy ten times higher. Mechanistically, the anti-RA effect of micelles was blocked by the co-treatment of AMPK inhibitor or palmitic acid, indicating that the mechanism of micelles was carried out through targeting mitochondrial, suppressing lipogenesis and finally inhibiting cellular proliferation. Taken together, our ROS-responsive nano-medicines represent an effective way of preferentially releasing prodrug at the inflammatory microenvironment and improving RA therapeutic efficacy.

Objective: The major barrier to transumbilical endoscopic surgery is external interference between the instrument handles around the umbilicus. We describe technique of totally transumbilical endoscopic cholecystectomy using improved instruments., Methods: New trocars (5 and 3 mm in diameter, respectively) without proximal seal system on the sleeves were designed for this procedure. The maximum diameters of the trocars were reduced to 8 and 5 mm, respectively. The instruments used in this study were 5 cm longer than commercially available instruments. Ten cases of totally transumbilical cholecystectomy were performed successfully., Results: All the gallbladders were removed successfully without severe bleeding during dissection, except one case of gallbladder wall perforation by cautery. Mean operating time was 62 +/- 25 min (range 45-110 min). All patients were satisfied with abdominal cosmetic results, discharged 48 h after the operation, and returned to work within seven postoperative days., Conclusions: External interference between trocars and instruments can be partially avoided by using the improved instruments. Totally transumbilical endoscopic cholecystectomy becomes feasible with this technique.

Objective: There has been great interest in natural orifice transluminal endoscopic surgery (NOTES) in recent years. We report another new approach--transumbilical endoscopic surgery (TUES)--which we have performed in 40 cases for liver cysts (3), bleeding ascites (1), chronic appendicitis (10), and gallbladder diseases (26)., Methods: Transumbilical endoscopic liver cyst fenestration, abdominal cavity exploration, appendectomy, and cholecystectomy were performed in a total of 40 patients., Results: All the operations were completed successfully except one case of intraoperative bleeding in TUES cholecystectomy which was converted to routine laparoscopic surgery. The operating times for TUES cholecystectomy, appendectomy, and liver cyst fenestration were 30-150 min,15-40 min, and 30-90 min, respectively. No postoperative bleeding or bile leakage occurred in this group of patients., Conclusions: Transumbilical endoscopic surgery is feasible, and would be another option for scarless abdominal surgery. TUES cholecystectomy is technically challenging. Careful selection of patients is important in the initial period of this technique.