Metabolic profiling putatively identifies plasma biomarkers of male infertility using UPLC-ESI-IT-TOFMS.

Male infertility has become a global health problem. Currently, the diagnosis of male infertility depends on the results of semen quality or requires invasive surgical intervention. The process is complex and time-consuming. Metabolomics is an emerging platform with unique advantages in disease diagnosis and pathological mechanism research. In this study, ultra-performance liquid chromatography-electrospray ionization-ion trap-time of flight mass spectrometry (UPLC-ESI-IT-TOFMS) combined with chemometrics methods was used to discover potential biomarkers of male infertility based on non-targeted plasma metabolomics. Plasma samples from healthy controls (HC, n = 43) and various types of infertile patients, i.e., patients having oligozoospermia (OS, n = 36), asthenospermia (AS, n = 56) and erectile dysfunction (ED, n = 45) were analyzed by UPLC-ESI-IT-TOFMS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed. The results of OPLS-DA showed that HCs could be discriminated from infertile patients including OS (R 2 = 0.903, Q 2 = 0.617, AUC = 0.992), AS (R 2 = 0.985, Q 2 = 0.658, AUC = 0.999) or ED (R 2 = 0.942, Q 2 = 0.500, AUC = 0.998). Some potential biomarkers were successfully discovered by variable selection methods and variable important in the projection (VIP) in combination with the T-test. Statistical significance was set at p < 0.05; the Benjamini-Hochberg false discovery rate was used to reduce type 1 errors resulting from multiple comparisons. The identified biomarkers were associated with energy consumption, hormone regulation and antioxidant defenses in spermatogenesis. To elucidate the pathophysiology of male infertility, relative metabolic pathways were studied. It was found that male infertility is closely related to disturbed phospholipid metabolism, amino acid metabolism, steroid hormone biosynthesis metabolism, metabolism of fatty acids and products of carnitine acylation, and purine and pyrimidine metabolisms. Plasma metabolomics provides a novel strategy for the diagnosis of male infertility and offers a new insight to study pathogenesis mechanism.

The survival and value of liver transplantation for liver carcinoma: a single-center experience.

UNLABELLED: Liver transplantation for liver carcinoma with cirrhosis is a treatment still in dispute. The objectives were to summarize the survival and cost of 50 liver transplant cases performed for liver carcinoma over nearly 3 years. METHODS: We performed 138 liver transplants from January 1999 to February 2002. There were 50 cases (36.2%) of liver carcinoma with HBV cirrhosis, which were divided into three stages based on the tumor pathology: Stage 1 cases showed a single mass (< or = 5 cm), 4 cases; Stage 2, a single mass > 5 cm or intrahepatic multiple masses without PV cancer embolus, 32 cases; and Stage 3: tumor invasion of the PV or perihepatic lymph nodes or organs, 14 cases. All patients received three to six courses of chemotherapy postoperatively. RESULTS: All four cases of stage 1 survived > 1 year; one of them is at 3 years with good liver function and tumor free. The mean half-year medical cost was $27.100 +/- 108 in stage 1. The half-year survival and medical costs were 62.5% and $31,500 +/- 260 in stage 2 and 15.0% and $35,500 +/- 134 in stage 3. CONCLUSION: Liver transplantation is an effective treatment for early-stage liver carcinoma, that achieves good medical and economic results, but should be limited to advanced liver cancer.

Variation of haemorheological parameters in renal and pancreatic rejection.

Abnormalities of haemorheology were found in animal and human recipients of kidney and/or pancreas allografts during rejection episodes. Thirteen diabetic canines received solitary pancreatic transplantation and another 13 diabetic and uremic canines underwent combined pancreas and kidney transplantation. Determination of haemorheological parameters was performed before and after operation respectively. During rejection episodes of kidney or pancreas allografts, the values of plasma viscosity, blood reductive viscosity and fibrinogen were significantly higher than those without rejection. On the basis of animal experiments, the determination of haemorheological parameters had been performed on 33 patients (30 receiving renal transplant, 2 pancreatic transplant alone and the remaining 1 combined renal and pancreatic transplant). Consecutive monitoring on these patients showed that a rise in the values of plasma viscosity, blood reductive viscosity and fibrinogen could be demonstrated during rejection episodes. The changes appeared one to three days prior to clinical manifestations and were in accordance with the termination of rejection. Our studies suggest that variation of haemorheological parameters are associated with rejection and the abnormal haemorheology may be an essential factor contributing to graft dysfunction. Moreover, the use of these assays will be beneficial to early diagnosis and better management of rejection in the future.

Presence of pro-vasopressin mRNA, neurophysin and arginine vasopressin in mouse anterior pituitary cells and the AtT-20 corticotrophic tumour cell line.

Pro-vasopressin mRNA, neurophysin and arginine vasopressin (AVP) were assayed in the mouse anterior pituitary gland, in mouse anterior pituitary cells in culture and in the AtT-20 corticotrophic tumour cell line. Northern blot analysis revealed the presence of an approximately 700 base pair pro-vasopressin mRNA in anterior pituitary and AtT-20 cells. Neurophysin, identified by immunoblots, and AVP, identified by high-performance liquid chromatography and cross-reactivity with AVP antiserum, were detected in anterior pituitary cells and AtT-20 cells. Immunocytochemical staining with anti-neurophysin showed that approximately 40-45% of the dissociated anterior pituitary cells in culture and greater than 95% of the AtT-20 cells were stained. Anterior pituitary cells in culture and AtT-20 cells had a basal level of release of AVP in the 0.01-0.1 nM range. These results indicate that anterior pituitary cells and AtT-20 cells have the ability to synthesize and process pro-vasopressin to AVP and neurophysin, endogenously.