Background: To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT). Methods: Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46 - 54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30 < 30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram. Results: HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively. Conclusion: Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.

Background: Diabetes or hypertension contributes to erectile dysfunction (ED). We hypothesized that excess reactive oxygen species (ROS) production evoked by diabetes combined with hypertension may further suppress endothelial nitric oxide (NO) expression/activity and promote oxidative stress in the ED penis. Methods: Twenty-four adult male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were divided into four groups: normal WKY, diabetic WKY, normal SHR and diabetic SHR. Intraperitoneal streptozotocin (65 mg/kg) was applied to induce type I diabetes. After 4-week diabetes and/or hypertension induction, we determined the intra-cavernous pressure (ICP) using electrical stimulation of cavernous nerves, intra-cavernosum NO amount using an electrochemical NO probe, and blood ROS using an ultrasensitive chemiluminescence-amplified analyzer. Western blot analysis and immunohistochemistry were used to explore the pathophysiologic mechanisms of inflammation, apoptosis and autophagy in the penis. A novel NO donor, CysaCysd Lu-5 (CCL5, (RCH₂CH₂S)(R’R”CHCH₂S)Fe(NO)₂, 1-4 µg), was intravenously administered to these ED rats for evaluating their ICP responses. Results: In the baseline status, the lucigenin- and luminol-amplified blood ROS were significantly enhanced in the diabetic SHR rats vs normal WKY rats. Significantly decreased ICP, eNOS expression and NO amount were found in the normal SHR, diabetic WKY, and diabetic SHR vs normal WKY rats. Intravenous NO donor L-Arginine markedly increased ICP and NO amount, whereas eNOS inhibitor, N_ω-Nitro-L-Arginine methyl ester hydrochloride depressed ICP in all four groups. Diabetes and/or hypertension alone increased fibrosis, proinflammatory NF-kB/ICAM-1 expression, mast cell numbers, CD68 expression and infiltration, Caspase 3-mediated apoptosis, Beclin-1/LC3-II–mediated autophagy and mild Nrf-2/HO-1 expression and depressed eNOS expression in the ED penis. The novel NO donor, CCL5, was more efficient than L-arginine to improve diabetes and/or hypertension–induced ED by the significant increase of ICP. Conclusion: Diabetes combined with hypertension synergistically exacerbated ED through enhanced oxidative stress, inflammation, apoptosis and autophagy and depressed eNOS activity and NO production.

Aim Enhancement of thromboxane A₂ (TXA₂) synthase (TXAS) activity, TXA₂ release, and thromboxane prostanoid (TP) receptor activation leads to vasoconstriction and oxidative injury. We explored whether genetic deletion of TXAS/TXA₂/TP signalling may reduce renal ischaemia/reperfusion (I/R) injury in mice. Materials and Methods Renal haemodynamics and function were evaluated in TXAS^+/+TP^+/+ (wild-type, WT), TXAS^−/− (TXS^−/−), TP^−/− and TXAS^−/−TP^−/− (double knockout, dKO) mice in response to intravenous TXA₂ mimetic-U46619 and 45-minute renal ischaemia and 4-hour reperfusion injury. We examined renal TXAS and TP expression, blood urea nitrogen (BUN) and creatinine, reactive oxygen species (ROS) amount, pro-inflammatory cytokines and pathophysiologic mechanisms, including apoptosis, autophagy and pyroptosis under I/R injury. Results Renal I/R enhanced the levels of TXAS, TP, nuclear factor-κB, nicotinamide adenine dinucleotide phosphate oxidase gp91, Bax/Bcl-2/caspase-3/apoptosis, Beclin-1/LC3-II/autophagy, caspase-1/gasdermin D/interleukin-1β/pyroptosis, renal thromboxane B₂ (TXB₂) concentration, ROS amount, plasma BUN, creatinine and TXB₂ and decreased renal endothelial nitric oxide synthase expression in WT mice. All these enhanced parameters were significantly decreased in three KO mice. Intravenous U46619 significantly decreased renal microcirculation and enhanced gp91 and Bax/Bcl-2 in WT and TXS^−/− but not TP^−/− in dKO mice. I/R significantly decreased renal microcirculation in all mice; however, the time for recovery to baseline renal blood flow level was significantly shortened in TXS^−/−, TP^−/−and dKO mice versus WT mice. Blockade of TXAS/TP signalling attenuated I/R-enhanced pro-inflammatory cytokine profile. Conclusion Blockade of TXAS/TXA₂/TP signalling confers renal protection against I/R injury through the actions of anti-oxidation, anti-inflammation, anti-apoptosis, anti-autophagy and anti-pyroptosis. Research idea and study design: T.H.C., Y.H.C., K.H.C., C.T.C.; data acquisition: T.H.C., Y.H.C.; data analysis/interpretation: T.H.C., K.H.C., C.T.C.; statistical analysis: T.H.C., C.T.C.; supervision or mentorship: K.H.C., C.T.C. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. ^* These senior authors contributed equally to this work.

Donor operation in adult living donor liver transplantation is associated with significant postoperative morbidity. To avoid laparotomy wound complications and shorten postoperative recovery, laparoscopic liver graft harvest has been developed recently. However, to determine the cut point of bile duct is challenging. Herein, we report the application of totally laparoscopic approach for right liver graft harvest in a donor with trifurcation of the bile duct. A19-year-old man volunteered for living donation to his father who suffered from hepatitis B virus-related cirrhosis of liver and hepatocellular carcinoma. The graft was 880 mL with a single right hepatic artery and portal vein. The graft to recipient weight ratio was 1.06. The middle hepatic vein was preserved for the donor and the liver remnant was 42.3%. Two branches of middle hepatic veins were > 5 mm in diameter and needed reconstruction with cryopreserved allograft. Ductoplasty using laparoscopic intracorporeal suture technique was done to achieve single orifice of the graft bile duct. The postoperative course was uneventful for the donor. This report adds evidence of the feasibility of pure laparoscopic right donor hepatectomy and describes the necessary steps for bile duct division in donors with trifurcation of bile duct.

Toll-like receptors (TLRs) play crucial roles in host immune defenses. Recently, TLR-mediated autophagy is reported to promote immune responses via increasing antigen processing and presentation in antigen presenting cells. The present study examined whether the synthetic TLR4 activator (CCL-34) could induce autophagy to promote innate and adaptive immunity. In addition, the potential of CCL-34 as an immune adjuvant in vivo was also investigated. Our data using RAW264.7 cells and bone marrow-derived macrophages showed that CCL-34 induced autophagy through a TLR4-NF-κB pathway. The autophagy-related molecules (Nrf2, p62 and Beclin 1) were activated in RAW264.7 cells and bone marrow-derived macrophages under CCL-34 treatment. CCL-34-stimulated macrophages exhibited significant antigen-processing activity and induced the proliferation of antigen-specific CD4+T cells as well as the production of activated T cell-related cytokines, IL-2 and IFN-γ. Furthermore, CCL-34 immunization in mice induced infiltration of monocytes in the peritoneal cavity and elevation of antigen-specific IgG in the serum. CCL-34 treatment in vivo did not cause toxicity based on serum biochemical profiles. Notably, the antigen-specific responses induced by CCL-34 were attenuated by the autophagy inhibitor, 3-methyladenine. In summary, we demonstrated CCL-34 can induce autophagy to promote antigen-specific immune responses and act as an efficient adjuvant.