Oxidized ATP Suppresses B Lymphocyte Activity to Attenuate Antibody-mediated Rejection of Kidney Allografts in Mice.

BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of renal allograft dysfunction and loss. Targeting B cells and/or donor-specific antibody removal using plasma exchange and anti-CD20 antibodies are increasingly used in clinical practice, but the efficacy remains limited. Recent studies suggest that targeting purinergic P2X7 receptor/ATP axis can have profound immune regulatory effects in transplant models, but the mechanisms involved remain incompletely defined. METHODS: Purified B cells were isolated from the spleen of Balb/C mice and cultured with oxidized ATP at different concentrations. Proliferation and differentiation of B cells were examined. Effects of oxidized ATP were examined in a presensitized animal model where kidney allograft rejection mimics aspects of clinical AMR. Histopathology was assessed at the time of rejection or on day 5 after kidney transplantation. Infiltrating immune cells in renal allografts were detected by flow cytometry. RESULTS: Oxidized ATP inhibited B-cell activation and proliferation in vitro, significantly attenuated histological signs of graft injury and prolonged kidney allograft survival. Mechanistically, oxidized ATP inhibited antibody secretion by activated B cells in response to lipopolysaccharide stimulation and markedly suppressed the production of donor-specific antibody in kidney allograft recipients. Oxidized ATP also reduced graft infiltration by other inflammatory cells. CONCLUSIONS: These findings provide evidence for the involvement of the purinergic P2X7 receptor pathway in AMR and suggest that targeting this pathways may have important clinical implications.

Novel deformable self-assembled magnetic anastomosis ring for endoscopic treatment of colonic stenosis via natural orifice.

BACKGROUND: Although endoscope-assisted magnetic compression anastomosis has already been reported for colonic anastomosis, there is no report on a single-approach operation using the natural orifice. AIM: To design a deformable self-assembled magnetic anastomosis ring (DSAMAR) for colonic anastomosis for use in single-approach operation and evaluate its feasibility and safety through animal experiments. METHODS: The animal model for colonic stenosis was prepared by partial colonic ligation in eight beagles. The magnetic compression anastomosis of their colonic stricture was performed by endoscopically assisted transanal implantation of the DSAMAR. The anastomotic specimen, obtained 2 wk after the operation, was observed by both the naked eye and a light microscope. RESULTS: The DSAMAR was successfully inserted into the proximal end of colon stenosis through the anus. The DSAMAR of seven dogs was successfully transformed into rings, while that of the remaining dog was removed after the first deformation failed. The rings were successfully retransformed after optimization. All animals underwent colonic anastomosis using the DSAMAR. No device-related or procedure-related adverse events were observed. The colostomy specimens of the experimental dogs were obtained 2 wk after the operation. Both gross and histological observations showed good anastomotic healing. CONCLUSION: The DSAMAR is a safe and feasible option for the treatment of colon stenosis. Its specific deformation and self-assembly capability maximize the applicability of the minimally invasive treatment.

Magnetic anchor technique assisted laparoscopic cholecystectomy in swine.

Magnetic anchor device based on the principle of magnet heteropolar attraction can assist laparoscopic surgery and reduce abdominal wall trauma. This study explored the feasibility of use of our self-designed magnetic anchor device for reduced-port laparoscopic cholecystectomy (LC) through animal experiments. Twelve experimental pigs (15-20 kg) were randomly divided into study group (magnetic anchor technique assisted 2-port LC, n = 6) and control group (conventional 3-port LC, n = 6). Operative time, intraoperative blood loss, and postoperative complications were compared between the two groups. LC was successfully performed in all 12 pigs. There was no significant between-group difference with respect to operative time (study group: 35.83 ± 5.12 min; control group: 34.50 ± 5.13 min, P = 0.662) or intraoperative blood loss (< 50 mL per animal in both groups). In the experimental group, there was no malfunction of the magnetic anchoring device, the use process was smooth, and the tissue traction and surgical field exposure were satisfactory. There were no perioperative complications such as bile duct injury, bile leakage, or bleeding in both groups. We demonstrated the feasibility of use of the self-designed magnetic anchor device in reduced-port LC. The device has important clinical application value.

A novel magnetic compression technique for cystostomy in rabbits.

Magnetic compression technique (MCT) is a popular new anastomosis method. In this paper, we aimed to explore the feasibility of use of MCT for performing cystotomy in rabbits. The parent magnets and daughter magnets for rabbit cystostomy were designed and manufactured according to the anatomical characteristics of rabbit lower urinary tract. Twelve female New Zealand rabbits were used as animal models. After anesthesia, a daughter magnet was inserted into the bladder through the urethra, and the parent magnet was placed on the body surface projection of the bladder over the abdominal wall. The two magnets automatically attract each other. Postoperatively, the state of magnets was monitored daily, and the time when the magnets fell off was recorded. Cystostomy with MCT was successfully performed in all twelve rabbits. The mean operation time was 4.46 ± 0.75 min. The magnets fell off from the abdominal wall after a mean duration of 10.08 ± 1.62 days, resulting in the formation of bladder fistula. Macroscopic and microscopic examination showed that the fistula was well formed and unobstructed. The junction between bladder and abdominal wall was tight and smooth. We provide preliminary experimental evidence of the safety and feasibility of cystostomy based on MCT.

Creation of gastroenteric anastomosis through natural orifice in rats by magnetic compression technique.

BACKGROUND: Being one of the core techniques of magnetic surgery, magnetic compression technique (MCT) has been used for digestive tract anastomosis reconstruction in experimental studies. This study verified the feasibility of gastroenteric anastomosis through natural orifice using MCT in rats. METHODS: The parent and daughter magnets were designed and manufactured for oral and anal insertion in 20 Sprague-Dawley rats. After anesthesia, the parent magnet was inserted into the colon spleen area through the anus, and the daughter magnet was inserted into the stomach through the mouth. Then the two magnets were positioned to attract each other and bind together. The position of the two magnets was monitored using X-ray. The time required for the formation of the anastomosis and expulsion of the magnets were recorded. 2 weeks later, the animal was sacrificed and the anastomotic specimen was obtained which was observed under naked eye and microscope. RESULTS: The gastroenteric anastomosis was successfully performed via natural orifices in 18 out of 20 rats. The mean time to construct the anastomosis was 3.78 ± 0.88 min. X-ray examination showed that the magnets were in the appropriate position in 17 rats. The magnets were excreted in 9.47 ± 1.62 days after surgery. The gross and microscopic examination of the specimen showed that the anastomoses were patent and the mucosa at the anastomotic was smooth. The mean bursting pressure of the anastomosis was 136.94 ± 6.79 mmHg. CONCLUSION: It is feasible to perform gastroenteric anastomosis through natural orifices by MCT.