Reproductive Deficits Induced by Prenatal Antimüllerian Hormone Exposure Require Androgen Receptor in Kisspeptin Cells.

Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterized by elevated androgens and antimüllerian hormone (AMH). These hormones remain elevated throughout pregnancy, and potential effects of hormone exposure on offspring from women with PCOS remain largely unexplored. Expanding on recent reports of prenatal AMH exposure in mice, we have fully characterized the reproductive consequences of prenatal AMH (pAMH) exposure throughout the lifespan of first- and second-generation offspring of both sexes. We also sought to elucidate mechanisms underlying pAMH-induced reproductive effects. There is a known reciprocal relationship between AMH and androgens, and in PCOS and PCOS-like animal models, androgen feedback is dysregulated at the level of the hypothalamus. Kisspeptin neurons express androgen receptors and play a critical role in sexual development and function. We therefore hypothesized that pAMH-induced reproductive phenotypes would be mediated by androgen signaling at the level of kisspeptin cells. We tested the pAMH model in kisspeptin-specific androgen receptor knockout (KARKO) mice and found that virtually all pAMH-induced phenotypes assayed are eliminated in KARKO offspring compared to littermate controls. By demonstrating the necessity of androgen receptor in kisspeptin cells to induce pAMH phenotypes, we have advanced understanding of the interactions between AMH and androgens in the context of prenatal exposure, which could have significant implications for children of women with PCOS.

Retracted: Anticancer Action of Psilostachyin-A in 5-Fluorouracil-Resistant Human Liver Carcinoma are Mediated Through Autophagy Induction, G2/M Phase Cell Cycle Arrest and Inhibiting Extracellular-Signal-Regulated Kinase/Mitogen Activated Protein Kinase (ERK/MAPK) Signaling Pathway.

An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. Reference: Jun Liu, Yan Liu, Yan Liu, Lei Huang, Guoliang Wang, Jun Wang, Xiangang Xu, Chengxian Shi, Jianzhao Huang: Anticancer Action of Psilostachyin-A in 5-Fluorouracil-Resistant Human Liver Carcinoma are Mediated Through Autophagy Induction, G2/M Phase Cell Cycle Arrest and Inhibiting Extracellular-Signal-Regulated Kinase/Mitogen Activated Protein Kinase (ERK/MAPK) Signaling Pathway. Med Sci Monit 2019; 25:6711-6718. 10.12659/MSM.916635.

Effect of prophylactic transcatheter arterial chemoembolization on hepatocellular carcinoma with microvascular invasion after R0 resection. A case-control study.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is thought to prevent recurrence of hepatocellular carcinoma (HCC), but its efficacy is a matter of controversy. OBJECTIVES: We investigated the effect of preventive TACE on the tumor, nodes, metastasis (TNM) classification in cases of stage II HCC (T2N0M0) after R0 resection. DESIGN AND SETTING: Case-control study conducted in a tertiary-level public hospital. METHODS: We analyzed recurrence rates and mortality rates over time for 250 consecutive cases of HCC in TNM classification cases of stage II HCC (T2N0M0) after R0 resection. These cases were divided into patients who underwent TACE (TACE+) and presented microvascular invasion (MVI+; n = 80); TACE+ but did not present MVI (MIV-; n = 100); MVI+ but did not undergo TACE (TACE-, n = 30); and TACE-/MVI- (n = 40). RESULTS: MVI+ patients in the TACE+ group had significantly lower recurrence rates and mortality rates at one, two and three years than those in the TACE- group (all P < 0.05). Among MVI- patients, the TACE+ group did not have significantly lower recurrence rates and mortality rates at one, two and three years than the TACE- group (all P > 0.05). Regardless of whether TACE was performed or not, MVI- patients had significantly lower recurrence rates and mortality rates at two and three years after their procedures than did MVI+ patients (all P < 0.05). CONCLUSION: Recurrence rates and mortality rates for MVI+ patients were significantly higher than for MVI- patients, beyond the first year after TACE. Postoperative adjuvant TACE may be beneficial for HCC patients with MVI.

Effect of prophylactic transcatheter arterial chemoembolization on hepatocellular carcinoma with microvascular invasion after R0 resection. A case-control study

ABSTRACT BACKGROUND: Transcatheter arterial chemoembolization (TACE) is thought to prevent recurrence of hepatocellular carcinoma (HCC), but its efficacy is a matter of controversy. OBJECTIVES: We investigated the effect of preventive TACE on the tumor, nodes, metastasis (TNM) classification in cases of stage II HCC (T2N0M0) after R0 resection. DESIGN AND SETTING: Case-control study conducted in a tertiary-level public hospital. METHODS: We analyzed recurrence rates and mortality rates over time for 250 consecutive cases of HCC in TNM classification cases of stage II HCC (T2N0M0) after R0 resection. These cases were divided into patients who underwent TACE (TACE+) and presented microvascular invasion (MVI+; n = 80); TACE+ but did not present MVI (MIV−; n = 100); MVI+ but did not undergo TACE (TACE−, n = 30); and TACE−/MVI− (n = 40). RESULTS: MVI+ patients in the TACE+ group had significantly lower recurrence rates and mortality rates at one, two and three years than those in the TACE- group (all P < 0.05). Among MVI- patients, the TACE+ group did not have significantly lower recurrence rates and mortality rates at one, two and three years than the TACE- group (all P > 0.05). Regardless of whether TACE was performed or not, MVI− patients had significantly lower recurrence rates and mortality rates at two and three years after their procedures than did MVI+ patients (all P < 0.05). CONCLUSION: Recurrence rates and mortality rates for MVI+ patients were significantly higher than for MVI− patients, beyond the first year after TACE. Postoperative adjuvant TACE may be beneficial for HCC patients with MVI.

Anticancer Action of Psilostachyin-A in 5-Fluorouracil-Resistant Human Liver Carcinoma are Mediated Through Autophagy Induction, G2/M Phase Cell Cycle Arrest and Inhibiting Extracellular-Signal-Regulated Kinase/Mitogen Activated Protein Kinase (ERK/MAPK) Signaling Pathway.

BACKGROUND Liver cancer is one of the most common malignancies around the world and one of the major causes of cancer related mortality. The objective of this study was to evaluate the anticancer effect of the natural compound psilostachyin-A on 5-fluorouracil-resistant human liver carcinoma cells and its effects on autophagy, cell cycle, caspase activation, and the ERK/MAPK signaling pathway. MATERIAL AND METHODS Cell Counting Kit 8 (CCK-8) assay was used to evaluate the effects on HepG2 cell viability at different doses of psilostachyin-A. Cell cycle analysis was performed using flow cytometry, and Transwell assay was used to check effects on cell invasion. Transmission electron microscopic studies were done to evaluate autophagy induced by psilostachyin-A, and the western blot method was carried out to evaluate the effects on autophagy and the ERK/MAPK signaling pathway. RESULTS CCK-8 assay revealed that the psilostachyin-A reduced the cell viability of HepG2 cancer cells in a dose dependent manner. Psilostachyin-A also reduced the colony forming potential of HepG2 cells, concentration dependently. The IC50 of psilostachyin was found to be 25 µM. The anticancer effects of psilostachyin-A were due to the induction of autophagy which was accompanied by enhancement of LC3B II expression. Psilostachyin also caused cell cycle arrest by enhancing the accumulation of HepG2 cells in the G2/M phase. Transwell assay showed that psilostachyin-A suppressed the invasion of HepG2 cells. The results also showed that psilostachyin-A could block the ERK/MAPK pathway, indicative of the cytotoxic effects of psilostachyin-A on liver cancer. CONCLUSIONS These preliminary observations suggested that psilostachyin-A might prove beneficial in the treatment of liver cancer.

Advantages of laparoscopic common bile duct exploration in common bile duct stones.

OBJECTIVE: To compare the efficacy, safety, and surgical outcomes of laparoscopic common bile duct exploration, endoscopic retrograde cholangiopancreatography, and open common bile duct exploration for treatment of common bile duct stones. METHODS: In total, 210 patients were prospectively randomized into 3 groups: laparoscopic common bile duct exploration, endoscopic retrograde cholangiopancreatography, and open common bile duct exploration. The primary outcome measures were the common bile duct stone clearance rate and the complication rate. The secondary outcome measures were mortality, total costs, and length of hospital stay. RESULTS: The success rates in the laparoscopic common bile duct exploration group (97.14%, 68 out of 70) and open common bile duct exploration group (98.57%, 69/70) were significantly higher than that in the endoscopic retrograde cholangiopancreatography group (85.71%, 60/70, both p < 0.05). The complication rates in the laparoscopic common bile duct exploration group (2.86%, 2/70) and open common bile duct exploration group (1.43%, 1/70) were significantly lower than that in the endoscopic retrograde cholangiopancreatography group (14.29%, 10/70, both p < 0.05). The success rate and complication rate were not significantly different between the laparoscopic common bile duct exploration group and open common bile duct exploration group (both p > 0.05). CONCLUSION: Laparoscopic common bile duct exploration provides an alternative therapeutic approach that was safer and more reliable, allowed for earlier recovery, and provided more cost-effective treatment of common bile duct stones.

Simplified pancreatoduodenectomy for complex blunt pancreaticoduodenal injury.

A 34-year-old man admitted to our department with complex blunt pancreaticoduodenal injury after a car accident. The wall of the first, second, and third portions of the duodenum was extensively lacerated, and the pancreas was longitudinally transected along the superior mesenteric vein-portal vein trunk. The pancreatic head and the uncinate process were devitalized and the distal common bile duct and the proximal main pancreatic duct were completely detached from the Vater ampulla. The length of the stump of distal common bile located at the cut surface of remnant pancreas was approximately 0.6 cm. A simplified Kausch-Whipple's procedure was performed after debridement of the devitalized pancreatic head and resection of the damaged duodenum in which the stump of distal common bile duct and the pancreatic remnant were embedded into the jejunal loop. Postoperative wound abscess appeared that eventually recovered by conservative treatment. During 16 months follow-up the patient has been stable and healthy. A simplified pancreaticoduodenectomy is a safe alternative for the Whipple procedure in managing complex pancreaticoduodenal injury in a hemodynamically stable patient.

[Altered expression of mitochondrial DNA encoding ATP 6, 8 and encoding protein in energy metabolism during cold preservation and reperfusion injury in rat liver transplantation].

OBJECTIVE: To study the expression changes of mitochondrial (mt) DNA encoding ATP6, 8 of hepatocytes in rat liver transplantation with cold preservation-reperfusion and explore the relationship between the expression of F(0)F(1)-ATPase induced by changes of ATP 6, 8 genes. METHODS: Orthotopic liver transplantation was performed in Wistar rats using the cuff technique as described by Kamada with modifications. Rats were randomly divided into four groups: group A (30 min cold preservation), group B (6 h cold preservation), group C (12 h cold preservation) and group D (sham operation). Samples were collected at 12 h, 24 h and on Day 3, 5 and 7 post-operation. The levels of mtDNA encoding ATPase 6, ATPase 8 mRNA were determined by RT-PCR. The expression changes of F(0)F(1)-ATPase protein were examined by Western blot. The ATP level of liver was observed in each group. RESULTS: The expression of ATPase 6, ATPase8 mRNA, F(0)F(1)-ATPase protein expression (ng/mg protein) and the level of ATP decreased (U/L) in groups A, B and C at 12 h post-operation. The lowest was in group C (0.81 +/- 0.08, 0.71 +/- 0.07, 0.47 +/- 0.07, 0.44 +/- 0.05) when compared with groups A (1.11 +/- 0.04, 1.07 +/- 0.07, 0.86 +/- 0.15, 0.70 +/- 0.11) and B (1.02 +/- 0.07, 0.90 +/- 0.10, 0.65 +/- 0.07, 0.55 +/- 0.08) (P < 0.05). The expression of ATPase 6, ATPase 8 mRNA increased after 24 h in groups A, B and C. The changes of F(0)F(1)-ATPase protein expression and ATP level were consistent with the expression of ATPase 6, ATPase 8 mRNA. Both ATPase 6 mRNA, ATPase 8 mRNA and F(0)F(1)-ATPase protein in group C increased slowly compared with groups A and B after 24 h. The mtDNA encoding ATPase 6, ATPase 8 changes of hepatocytes in rats liver transplantation with cold preservation-reperfusion suggested that mitochondrial function disorders are related to the changes of mitochondrial DNA encoding ATPase6, ATPase8. mtDNA encoding ATPase 6, ATPase 8 genes of hepatocytes decreased significantly and F(0)F(1)-ATPase protein expression decreased remarkably and resulted in the decrease of ATP levels. The energy deficiency led to liver injury during cold preservation-reperfusion in rats liver transplantation. The injury of liver was more obvious with the prolongation of cold preservation period. CONCLUSION: The abnormal expressions of mtDNA ATPase 6, ATPase 8 genes are important causes of the changes of F(0)F(1)-ATPase protein expression resulting in a disorder of mitochondrial energy metabolism.

[Effect of Salviae miltiorrhizae on mRNA expression of inducible nitric oxide synthase and organ injury in rats with severe acute pancreatitis].

OBJECTIVE: To investigate the relationship between mRNA expression of inducible nitric oxide synthase (iNOS) and organ injury, and the effect of Salviae Miltiorrhizae on iNOS mRNA in severe acute pancreas (SAP) rats. METHODS: Forty-five Wistar rats were randomly divided into 3 groups, the model group (MG), the Salviae Miltiorrhizae group (SMG), and the control group (CG), with 15 rats in each group. Rats in MG and SMG were established to SAP model by intraductal injection with 5% sodium taurocholate in a dose of 1.0 ml/kg, while rats in CG were merely performed sham-operation. Immediately after modeling, rats in SMG were injected with Salviae Miltiorrhizae injection (SMI) 2 ml/kg every 6 h for 4 times in total, but to rats in other two groups same volume of normal saline were administered. The level of serum amylase (AMY), nitric oxide (NO) and the volume of ascites of rats were determined 24h after modeling, and intensity of iNOS mRNA expression in pancreas, lung and kidney were detected in the same time using in situ hybridization and image analysis. The pathologic change was observed as well. RESULTS: The volume of ascites and serum levels of AMY and NO in MG were significantly higher then those in SMG and CG (P < 0.05 and P <0.01). The expression of iNOS mRNA in pancreas, lung and kidney increased in MG and SMG, it was significantly higher in MG than that in SMG. And the pathological change of pancreas, lung and kidney in SMG was milder than that in MG. CONCLUSIONS: Over-expression of iNOS mRNA could cause excessive synthesis of NO, and lead to injury of pancreas, lung and kidney in SAP. Salviae Miltiorrhizae in early stage of the disease can inhibit the over-expression of iNOS mRNA to ameliorate the injury of the pancreas, lung and kidney.