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Abstract Background Endometrial carcinoma is one of the most common gynecological malignancies in women. The diagnosis of the disease at early or premalignant stages is crucial for the patient's prognosis. To date, diagnosis and follow-up of endometrial carcinoma and hyperplasia require invasive procedures. Therefore, there is considerable demand for the identification of biomarkers to allow non-invasive detection of these conditions. Methods In this study, we performed a quantitative proteomics analysis on serum samples from simple endometrial hyperplasia, complex endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma patients, as well as healthy women. Serum samples were first depleted of high-abundance proteins, labeled with isobaric tags (iTRAQ™), and then analyzed via two-dimensional liquid chromatography and tandem mass spectrometry. Protein identification and quantitation information were acquired by comparing the mass spectrometry data against the International Protein Index Database using ProteinPilot software. Bioinformatics annotation of identified proteins was performed by searching against the PANTHER database. Results In total, 74 proteins were identified and quantified in serum samples from endometrial lesion patients and healthy women. Using a 1.6-fold change as the benchmark, 12 proteins showed significantly altered expression levels in at least one disease group compared with healthy women. Among them, 7 proteins were found, for the first time, to be differentially expressed in atypical endometrial hyperplasia. These proteins are orosomucoid 1, haptoglobin, SERPINC 1, alpha-1-antichymotrypsin, apolipoprotein A-IV, inter-alpha-trypsin inhibitor heavy chain H4, and histidine-rich glycoprotein. Conclusions The differentially expressed proteins we discovered in this study may serve as biomarkers in the diagnosis and follow-up of endometrial hyperplasia and endometrial carcinoma.

Brain aging is accompanied by alternations of brain structure, functions and the cognitive impairment. With respect to cognitive decline, the elderly population is far from homogeneous, as well as heterogeneous, which presents successful aging, normal aging, mild cognitive impairment and Alzheimer's disease. Studies demonstrated that higher serum leptin levels are associated with normal cognition in older adults without significant neurological conditions, while it is lower in most mild cognitive impairment patients. Leptin can improve cognitive disorders and referred to as a potential cognitive enhancer. Therefore, low level of leptin plays an significant role in cognitive impairment development in elderly people.

Objective: To evaluate the risk of the occurrence of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer in the oral HPV carriers through a population-based investigation in Shanghai., Methods: A total of 1200 cases of outpatients who attended the annual cervical examination and 50 preoperational cases of inpatients with CINIII or invasive cervical cancer were enrolled from three clinical centers in Shanghai. The oral HPV infection was determined by real-time PCR. In 1200-case cross-sectional study, the incidence rate of CIN was compared between the oral HPV positive and negative cohort. In 1250-case case-control study, the positive rate of oral HPV DNA test was compared among normal control group, CINI-III, and invasive cancer case groups, and all odds ratio (OR) values were calculated, respectively. The HPV transmission-related demographic and behavioral characters of the oral HPV carriers were also analyzed., Results: The oral HPV carriers accounted for 5.9% (71/1200) of the investigated outpatients. The oral HPV DNA positive rates were gradually increased with the cervical disease grades, which were 5.8% (68/1182, normal), 2/13 (CIN I), 1/5 (CINII), 31.4% (11/35, CINIII) and 5/15 (invasive cancer). In cross-sectional cohort studies, the relative risks (RR) of CINI,II were 2.9 and 4.0 for oral HPV carriers, respectively. In case-control study, the OR values for CINI-III and invasive cervical cancer were 3.1(95%CI: 1.6-10.1), 4.2(95%CI: 1.7-28.4), 7.1(95%CI: 4.8-19.8) and 10.1(95%CI: 3.2-32.1), respectively. The oral sex and multi-sexual partner were two major risk factors for the oral and cervical HPV co-infection, HPV-related cervical cancer and precancerous diseases according to behavioral analysis., Conclusions: There are complicated transmission pathways between oral and cervical HPV. Oral HPV carriers should be intensively followed up and their oral HPV infection and HPV-related cervical diseases should be treated together.

Objective: To explore the role and mechanism of Duffy antigen receptor for chemokines (DARC) of tissue in promoting the inflammatory reaction of the limb with venous hypertension., Methods: moral arteriovenous fistula was surgically created to establish the rat model of venous hypertension. A total of 36 SD rats were randomly divided into pcDNA3.1-DARC (Group A), empty plasmid of pcDNA3.1 (Group B) and control (Group C) groups. The animals were sacrificed at Days 14 and 42 post-operation respectively. The expressions of DARC at the RNA and protein level were detected by real-time polymerase chain reaction (PCR) and Western blot. And the serum level of interleukin (IL)-8 was detected by enzyme linked immunosorbent assay (ELISA) and the degrees of apoptosis and leukocytic infiltration of local tissue were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and hematoxylin and eosin (HE) staining., Results: With the elapsing time of venous hypertension, the DARC expression in tissue, the extent of apoptosis and leukocytic infiltration in tissue showed an increasing trend in Groups A and B. Group A was obviously higher than Group B during the corresponding period. And the differences were statistically significant (P < 0.05). The serum levels of IL-8 of Groups A and B showed a decreasing trend. And Group A was obviously lower than Group B. Both groups were higher than the control group. The differences were statistically significant (P < 0.05)., Conclusions: The level of DARC in tissue and the degree of inflammatory reaction of venous hypertension have a positive correlation. And DARC may promote the development of venous hypertension inflammation through augmenting the adhesion and migration of leukocytes.

Objective: To assess the feasibility, safety and outcome of anatomical laparoscopic left lateral hepatic lobectomy for benign and malignant liver tumors., Methods: From April 2005 to May 2008, 11 patients (7 male, 4 female; mean age 51.7 years) underwent anatomical laparoscopic left lateral hepatic lobectomy. Four patients presented with hepatocellular carcinoma and cirrhosis, while 1 patient had metastatic liver tumors from postoperatively colon cancer, five patients had hemangioma (2 cases with gallstones underwent cholecystectomy), 1 patient had a huge symptomatic angiolipoleiomyoma. Mean tumor size was 5.8 cm (range 2.1 to 12.0 cm). All the lesions were localized in the anatomical left lateral lobe (segments II to III)., Results: The mean operative time was 147 min (range 120 to 180 min). There were no intraoperative or postoperative complications, and blood transfusions were not required. The mean postoperative hospital stay was 5.9 days., Conclusions: Anatomical laparoscopic left lateral hepatic lobectomy are feasible and safety.

Objective: In cervical lesions, the overexpression of p16INK4a has been reported to be closely associated with human papillomavirus (HPV) infection. This study is designed to evaluate the role of p16INK4a as a biomarker in liquid-based cervical cytology screening., Methods: Seventy-four specimens from the patients in our hospital were collected for this study. After cytological examination with liquid-based cervical smears, high-risk HPV (HR-HPV) DNA was then detected by Hybrid Capture II assay, and the rest cells were immunostained for p16INK4a., Results: Of the 74 specimens, 10 were diagnosed as negative, 15 as atypical squmous cells of undetermined significance (ASC-US), 28 as low-grade squamous intraepithelial lesion (LSIL), 5 as atypical squmous cells which could not be excluded as HSIL (ASC-H), 11 high-grade squamous intraepithelial lesion (HSIL) and 5 as squamous cell carcinoma (SCC). The positive specimens of p16INK4a were 2, 5, 8, 3, 9, 5, respectively, in the above subgroups; meanwhile, the positive specimens of HR-HPV were 1, 4, 9, 3, 7, 5, respectively, in the above groups. The positive rate of both p16INK4a and HR-HPV in HSIL, ASC-H and SCC were obviously higher than that in LSIL, ASC-US and negative cases., Conclusion: Positive rate of p16INK4a and HR-HPV is highly correlated with the grade of the cervical lesion. p16INK4a immunocytochemical staining may be used as a biomarker to increase the sensitivity of cervical cytology screening and the specificity of HPV test.

Aim: To report a retrospective analysis of preliminary results of 36 patients who received sirolimus (SRL, Rapamune, rapamycin) in a consecutive cohort of 248 liver allograft recipients., Methods: Thirty-six liver transplant patients with hepatocellular carcinoma (HCC) who were switched to SRL-based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation (OLT) were divided into group A (n = 11), those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B (n = 18), and those who developed renal insufficiency caused by calcineurin inhibitor (CNI) were assigned to group C (n = 7) after OLT., Results: The patients were followed up for a median of 10.4 mo (range, 3.8-19.1 mo) after conversion to SRL therapy and 12.3 mo (range, 5.1-34.4 mo) after OLT. Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% (12/18) patients (2 with progressive tumor, 7 with stable tumor and 3 without tumor) were still alive due to conversing to SRL and/or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia (n = 2), anemia (n = 8), and oral aphthous ulcers (n = 7) found in our cohort were easily manageable., Conclusion: The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.

Objective: To analyze the risk factors influencing the prognosis of orthotopic liver transplantation for hepatocellular carcinoma (HCC) and sum up the relevant clinical experience in diagnosis and treatment of HCC., Methods: The clinical data of 198 HCC patients, 177 males and 21 females, aged 49 (24-83), were analyzed., Results: The 0.5-, 1-, and 2-year survival rates were 89%, 78%, and 65 respectively. The rates of disease-free survival (DFS) were 85%, 73, and 67% respectively. Univariate analysis revealed that tumor size, presence of vascular invasion, Edmondson grade, TNM classification, and preoperative alpha-fetoprotein (AFP) were significantly related to DFS, and the 4 foregoing factors were also related to the survival rate. Cox regression analysis suggested that presence of vascular invasion was an independent prognostic factor of survival rate and DFS., Conclusion: Vascular invasion plays a leading role in evaluating the prognosis of orthotopic liver transplantation for HCC. It is important to discover the micro-metastasis and explore more effective approaches to prevent recurrence after transplantation.

Objective: To investigate the measures to further improve the therapeutic efficacy of liver transplantation., Methods: The clinical data of 203 consecutive cases of orthotopic liver transplantation (OLT) performed in Zhongshan Hospital, Fudan University April 2001 to October 2004, with the indications for considering OLT of hepatocellular carcinoma (HCC) (142 cases), liver cirrhosis (36 cases), fulminant hepatic failure (7 cases), Wilson's disease (6 cases), and other end-stage liver diseases (12 cases), including 199 cases of cadaveric OLT, inclusive of 2 cases of reduced-size and 1 case of splitting liver transplantation, and 4 cases of living-donor liver transplantation, were retrospectively analyzed. Multivariate analysis using Cox proportional hazards regression model was applied to determine the risk factors predicting liver transplantation prognosis for HCC., Results: For the whole group of the 201 patients, the 1-year and 2-year cumulative survival rates were 85.0% and 82.4% respectively and the rejection rate was 12.3%. In the HCC group the 1- and 2-year cumulative survival rates were 80.2% and 78.4%, and the 1- and 2-year disease-free survival (DFS) rates were 85.3% and 80.3% respectively. HCC recurrence was observed in 20 patients after OLT with a recurrence rate of 14.1%. Multivariate analysis revealed that the tumor size and portal vein tumor thrombus were the most independent and statistically significant factors affecting the DFS., Conclusion: OLT may be the most effective treatment option for patients with end-stage liver diseases and may also provide the opportunity of curative treatment or survival improvement for selected patients with hepatic malignancies.

Background: Selection of patients with hepatocellular carcinoma (HCC) for orthotopic liver transplantation (OLT) remains controversial. Since there is a trend to expand the transplant criteria for HCC patients, we reviewed the data of patients with HCC who had received OLT at our institute to determine their survival and prognostic factors., Methods: A total of 67 patients with HCC who had undergone OLT from April 2001 through December 2003 were reviewed retrospectively. Selection OLT candidates with HCC was dependent on the anatomical characteristics and/or the severity of underlying liver cirrhosis. The 67 patients were followed up for more than 6 months after transplantation. Their survival rate was calculated by the Kaplan-Meier method. Univariate and multivariate analyses using the Cox proportional hazards regression model were performed to reveal the factors affecting the survival rate., Results: No perioperative death occurred in this series. The 1- and 2-year cumulative survival rates were 90.0% and 65.6%, and the disease-free survival (DFS) rates were 77.5% and 62.5% respectively. Univariate analysis revealed the tumor size, portal vein tumor thrombus (PVTT), serum alpha-fetoprotein level, bilobular distribution of tumors, pTNM stage and histological differentiation were statistically significant factors affecting the DFS (P < 0.05). Multivariate analysis showed tumor size and PVTT were independent and statistically significant factors affecting the DFS (P = 0.005 and 0.010, respectively). In this series, all but 2 received systemic chemotherapy, among them 13 had tumor recurrence within 8 months after OLT., Conclusions: OLT is indicated for patients with HCC, even for some patients with end-stage liver disease who may survive longer without tumor recurrence. Adjuvant chemotherapy may decrease the recurrence of HCC after OLT.