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1.  Can steroidal ovarian suppression during the luteal phase after oocyte retrieval reduce the risk of severe OHSS? 
Ovarian stimulation in IVF cycle results in luteal supraphysiological steroid concentrations especially for high response patients. The aim of this study was to evaluate the efficacy of ovarian steroid hormone suppression in luteal phase after oocyte retrieval for preventing severe ovarian hyperstimulation syndrome (OHSS) in high-risk patients with embryo cryopreservation.
281 patients with high risk of OHSS were enrolled in this study among 4735 infertile women undergoing their first IVF treatment. The subjects were allocated into treatment and control group. The treatment group (n = 161) received letrozole (n = 43), mifepristone (n = 51), cetrotide (n = 39) and three-drug combinations (n = 28) during the luteal phase after oocyte retrieval, respectively. The control group (n = 120) received no medicine. Fertilization rate, good embryo rate, serum steroid concentration, clinical outcome, and incidence of severe OHSS were compared between the two groups.
On days 2, 5 and 8 after oocyte retrieval, serum estradiol levels in the letrozole and three-drug combination therapy group were significantly lower than in the other three groups at the same time (P < 0.001, respectively). There were no significantly difference of serum luteinizing hormone concentration on days 2, 5 and 8 and progesterone concentration on day 8 after oocyte retreival among the five groups (P > 0.05, respectively). Compared with the control group, the incidence of severe OHSS, the paracentesis rate, the duration of hospitalization and the days of luteal phase in each subgroup of treatment groups was not significantly decreased (P > 0.05, respectively).
Our findings indicate that steroidal ovarian suppression in luteal phase after oocyte retrieval seems to be unable to prevent severe OHSS in high-risk patients with embryo cryopreservation.
PMCID: PMC4579791  PMID: 26400057
Ovarian hyperstimulation syndrome; In vitro fertilization; Luteal phase; Mifepristone; Aromatase inhibitors; Gonadotropin-releasing hormone antagonist; Prevention
2.  Radiation-induced hepatitis B virus reactivation in hepatocellular carcinoma: A case report 
Oncology Letters  2015;10(5):3213-3215.
Hepatitis B virus (HBV) reactivation associated with radiotherapy is rare. The present study reports the case of a 46-year-old man that experienced fatal HBV reactivation. The patient suffered from hepatocellular carcinoma (HCC) with portal vein tumor thrombus, which was treated by radiotherapy at a daily fraction of 2 Gy over 5 weeks, up to a total radiation dose of ~50 Gy. The patient presented with fatigue, yellow sclera and abdominal distension ~8 weeks subsequent to the administration of radiotherapy. The liver function tests, including the level of total bilirubin and prothrombin time, suggested acute-on-chronic liver failure. The serum HBV-DNA level had also increased between undetectable levels and 7.2×104 copies/ml. Although the present patient with HCC was treated with 0.5 mg/day entecavir for 8 weeks, in addition to radiotherapy, radiation-induced HBV reactivation occurred. The condition of the patient worsened gradually. The present study emphasizes the importance of liver function and HBV-DNA screening and pre-emptive antiviral prophylaxis prior to radiotherapy in patients with HCC.
PMCID: PMC4665339  PMID: 26722314
radiation; reactivation; hepatitis B virus; hepatocellular carcinoma
3.  A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice 
PLoS ONE  2015;10(7):e0130643.
It is well documented that serotonin (5-HT) plays an important role in psychiatric illness. For example, myalgic encephalomyelitis (ME/CFS), which is often provoked by infection, is a disabling illness with an unknown aetiology and diagnosis is based on symptom-specific criteria. However, 5-HT2A receptor expression and peripheral cytokines are known to be upregulated in ME. We sought to examine the relationship between the 5-HT system and cytokine expression following systemic bacterial endotoxin challenge (LPS, 0.5mg/kg i.p.), at a time when the acute sickness behaviours have largely resolved. At 24 hours post-injection mice exhibit no overt changes in locomotor behaviour, but do show increased immobility in a forced swim test, as well as decreased sucrose preference and reduced marble burying activity, indicating a depressive-like state. While peripheral IDO activity was increased after LPS challenge, central activity levels remained stable and there was no change in total brain 5-HT levels or 5-HIAA/5-HT. However, within the brain, levels of TNF and 5-HT2A receptor mRNA within various regions increased significantly. This increase in receptor expression is reflected by an increase in the functional response of the 5-HT2A receptor to agonist, DOI. These data suggest that regulation of fatigue and depressive-like moods after episodes of systemic inflammation may be regulated by changes in 5-HT receptor expression, rather than by levels of enzyme activity or cytokine expression in the CNS.
PMCID: PMC4493081  PMID: 26147001
4.  Cetrotide administration in the early luteal phase in patients at high risk of ovarian hyperstimulation syndrome: A controlled clinical study 
The aim of the present pilot study was to assess the feasibility and efficacy of Cetrotide administration in the early luteal phase in patients at high risk of ovarian hyperstimulation syndrome (OHSS), undergoing embryo cryopreservation following superovulation. A total of 135 patients at high risk of OHSS and undergoing embryo cryopreservation were divided into two groups. In the treatment group (n=39), the patients received daily subcutaneous injections of 0.25 mg Cetrotide between days 1 and 5 following ooctye retrieval, and volume expansion and symptomatic treatment were also provided. In the control group (n=96), the patients received routine treatments, including volume expansion therapy. The serum steroid hormone concentrations of the patients were measured on days 2, 5 and 8 following ooctye retrieval, while the incidence of moderate or severe OHSS, self-evaluated clinical symptoms and various clinical indicators were recorded. The serum estradiol (E2), luteinizing hormone and progesterone levels in the treatment group on days 2, 5 and 8 following oocyte retrieval were not found to differ significantly when compared with the patients in the control group (P>0.05). The incidence of severe OHSS did not differ significantly between the two groups (P>0.05). The average length of hospital stay and length of luteal phase were not found to be significantly different between the treatment and control groups (P>0.05). In conclusion, Cetrotide injections in the early luteal phase did not alter the serum steroid levels of patients at high risk of OHSS undergoing embryo cryopreservation, and were unable to reduce the incidence of severe early OHSS. However, further randomized studies are required to evaluate the effectiveness of Cetrotide in the prevention of OHSS.
PMCID: PMC4217764  PMID: 25371744
gonadotropin-releasing hormone antagonist; ovarian hyperstimulation syndrome; in vitro fertilization; luteal phase; prevention
5.  Magnetic endoscopic imaging vs standard colonoscopy: Meta-analysis of randomized controlled trials 
AIM: To assess the theoretical advantages of magnetic endoscope imaging (MEI) over standard colonoscopies (SCs) and to compare their efficacies.
METHODS: Electronic databases, including PubMed, EMBASE, the Cochrane library and the Science Citation Index, were searched to retrieve relevant trials. In addition, abstracts from papers presented at professional meetings and the reference lists of retrieved articles were reviewed to identify additional studies. The meta-analyses were performed using RevMan 5.1. A random effect model with the Mantel-Haenszel method was used for pooling dichotomous and continuous data. A sensitivity analysis was performed by excluding the trials with a small number of patients and by excluding the trials performed by inexperienced providers.
RESULTS: Eight randomized controlled trials (RCTs), including 2967 patients, were included in the meta-analysis to compare cecal intubation rates and times, sedation dose, abdominal pain scores and the use of ancillary maneuvers between MEI and SC. The overall OR was 1.92 (95%CI: 1.13-3.27, eight RCTs), as indicated by the cecal intubation rate of MEI compared with SC, but MEI did not have any distinct advantage over SC for cecal intubation time (MD = -0.07, 95%CI: -0.16-0.02; three RCTs). MEI did not generally result in lower pain scores. Outcomes were also analyzed for the two subgroups based on the endoscopists’ experience level to evaluate cecal intubation rates. MEI presented better outcomes for non-experienced colonoscopists than experienced colonoscopists.
CONCLUSION: The real-time magnetic imaging system is of benefit in training and educating inexperienced endoscopists and improves the cecal intubation rate for experienced and inexperienced endoscopists.
PMCID: PMC3819558  PMID: 24222966
Colonoscope; Magnetic endoscope imaging; Magnetic; Standard colonoscope; Meta-analysis
6.  Does the variable-stiffness colonoscope makes colonoscopy easier? A meta-analysis of the efficacy of the variable stiffness colonoscope compared with the standard adult colonoscope 
BMC Gastroenterology  2012;12:151.
The variable-stiffness colonoscope (VSC) appears to have advantages over the standard adult colonoscope (SAC), although data are conflicting. To provide a comprehensive up-to-date review, we conducted a meta-analysis to compare the efficacies of the VSC and SAC.
Electronic databases, including PubMed, EMBASE, the Cochrane library and the Science Citation Index, were searched to retrieve relevant trials. In addition, meeting abstracts and the reference lists of retrieved articles were reviewed for further relevant studies.
Eight randomized controlled trials (RCTs), enrolling a total of 2033 patients, were included in the meta-analysis. There was no significant heterogeneity among these studies. The cecal intubation rate was higher with the use of VSC (RR = 1.03, 95% CI 1.01 to 1.06, 8 RCTs). The VSC was also associated with fewer position changes made during colonoscopy. Time to cecal intubation was similar with VSC and SAC (WMD −0.54, 95% CI −1.40 to 0.32) but shorter in subgroup analysis with the use of VSC (WMD = −1.36, 95% CI −2.29 to −0.43). Sedation dose used with the two types of instruments showed no evidence of differences either. For all trials, only patients were blinded because of the nature of the interventions.
Use of the VSC significantly improved the cecal intubation rate and reduced ancillary maneuvers made during the procedure. Cecal intubation time was similar for the two colonoscope types over all trials, whereas a shortened time with the use of the adult VSC was seen in subgroup analysis.
PMCID: PMC3503737  PMID: 23095461
Colonoscope; Variable-stiffness colonoscope; Stiffness; Meta-analysis
7.  Thyroid transcription factor 1 represses the expression of Ki-67 and induces apoptosis in non-small cell lung cancer 
Oncology Reports  2012;28(5):1544-1550.
The thyroid transcription factor 1 (TTF-1) gene is associated with the differentiation of lung epithelial cells and has been reported to be an independent prognostic factor for lung adenocarcinoma patients. The aim of the present study was to detect the expression of TTF-1 in human lung cancer cell lines and to evaluate the association of overexpressed TTF-1 with Ki-67 and apoptosis in the A549 cell line. We also investigated the expression of TTF-1 and Ki-67 in Xuanwei lung adenocarcinoma. TTF-1 mRNA expression was evaluated in 10 non-small cell lung cancer (NSCLC) cell lines by quantitative real-time RT-PCR (qRT-PCR). Overexpression of TTF-1 in A549 cells was achieved by transient transfection. The TTF-1 and Ki-67 proteins were detected by immunohistochemistry and apoptosis was detected by flow cytometry. We also investigated immunohistochemically the expression of TTF-1 and Ki-67 in 62 resected cases of Xuanwei lung adenocarcinoma. Overall the expression of TTF-1 mRNA in the 10 cell lines was low. Overexpression of TTF-1 mRNA was found only in 3 (30%) of 10 NSCLC cell lines, including 1 (25%) of 4 adenocarcinoma cell lines. A549 cells overexpressing TTF-1 were found to have repressed expression of Ki-67 (P=0.012) and increased apoptosis (P=0.000). Immunohistochemical analysis of resected cases of Xuanwei lung adenocarcinoma (n=62) showed the expression of TTF-1 in 58 (93%) of 62 and Ki-67 in 22 (35%) of 62. Patients with strong immunohistochemical expression TTF-1 were statistically associated with well-differentiated phenotype (P=0.006) and inverse correlation with Ki-67 expression (P=0.016). These data suggest that TTF-1 may serve as a tumor suppressor gene based on its inverse correlation with Ki-67 proliferative activity and increase of cellular apoptosis.
PMCID: PMC3583567  PMID: 22940844
thyroid transcription factor 1; Ki-67; apoptosis; non-small cell lung cancer lines; Xuanwei lung adenocarcinoma
8.  Th17 promotes acute rejection following liver transplantation in rats*  
T help cell 17 (Th17), recently identified as a new subset of CD4+ T cells, has been implicated in autoimmune diseases, tumor immunity, and transplant rejection. To investigate the role of Th17 in acute hepatic rejection, a rat model of allogeneic liver transplantation (Dark Agouti (DA) to Brown Norway (BN)) was established and isogeneic liver transplantation (BN to BN) was used as controls in the study. The expression of Th17-related cytokines in the liver and peripheral blood was determined by immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assay (ELISA), or real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Strong expression of interleukin-17A (IL-17A), IL-6, transforming growth factor-β (TGF-β), IL-8, and myeloperoxidase (MPO) was observed in liver allografts. The ratios of Th17 to CD4+ lymphocytes in the liver and peripheral blood were dramatically increased in the allograft group compared with the control (P<0.01). Secreted IL-17 and IL-6 in liver homogenate and serum were significantly elevated in the allograft group, while secreted TGF-β was increased in liver homogenate and decreased in serum compared with the control (P<0.01). The messenger RNA (mRNA) levels of IL-17, IL-21, and IL-23 were enhanced in the allografts compared with the control (P<0.01). Correlation analysis showed significant correlations between IL-17 and IL-6 and TGF-β and between IL-17 and IL-21 and IL-23. The present study demonstrates that Th17 plays a role in promoting rat liver allograft rejection.
PMCID: PMC2970890  PMID: 21043049
Th17; Liver transplantation; Rejection; Transplant immunology
9.  Controversies about the use of serological markers in diagnosis of inflammatory bowel disease 
The serological markers are increasingly used in diagnosis of inflammatory bowel disease (IBD). D-lactate and diamine oxidase are new indicators that can be used to reveal the damage to intestinal mucosa and permeability alteration in IBD. Although the two biological markers seem more sensitive, recent clinical trials and animal experiments have shown controversies about the use of them in diagnosis of IBD. Therefore, these markers should be interpreted cautiously and further prospective studies are needed to establish their clinical role in diagnosis of IBD.
PMCID: PMC2806570  PMID: 20066751
Inflammatory bowel diseases; D-lactate; Diamine oxidase; Intestinal permeability; Diagnosis
12.  A Randomized Controlled Phase IIb Trial of Antigen-Antibody Immunogenic Complex Therapeutic Vaccine in Chronic Hepatitis B Patients 
PLoS ONE  2008;3(7):e2565.
The safety of the immune complexes composed of yeast-derived hepatitis B surface antigen (HBsAg) and antibodies (abbreviated as YIC) among healthy adults and chronic hepatitis B patients has been proved in phase I and phase IIa trial. A larger number of patients for study of dosage and efficacy are therefore needed.
Methods and Principal Findings
Two hundred forty two HBeAg-positive chronic hepatitis B patients were immunized with six injections of either 30 µg YIC, 60 µg of YIC or alum adjuvant as placebo at four-week intervals under code. HBV markers and HBV DNA were monitored during immunization and 24 weeks after the completion of immunization. The primary endpoint was defined as loss of HBeAg, or presence of anti-HBe antibody or suppression of HBV DNA, while the secondary endpoint was both HBeAg seroconversion and suppression of HBV DNA. Statistical significance was not reached in primary endpoints four weeks after the end of treatment among three groups, however, at the end of follow-up, HBeAg sero-conversion rate was 21.8%(17/78) and 9% (7/78) in the 60 µg YIC and placebo groups respectively (p = 0.03), with 95% confidence intervals at 1.5% to 24.1%. Using generalized estimating equations (GEEs) model, a significant difference of group effects was found between 60 µg YIC and the placebo groups in terms of the primary endpoint. Eleven serious adverse events occurred, which were 5.1%, 3.6%, and 5.0% in the placebo, 30 µg YIC and 60 µg YIC groups respectively (p>0.05).
Though statistical differences in the preset primary and secondary endpoints among the three groups were not reached, a late and promising HBeAg seroconversion effect was shown in the 60 µg YIC immunized regimen. By increasing the number of patients and injections, the therapeutic efficacy of YIC in chronic hepatitis B patients will be further evaluated.
Trial Registration ChiCTR-TRC-00000022
PMCID: PMC2430617  PMID: 18596958
13.  Characterization and enrichment of hepatic progenitor cells in adult rat liver 
World Journal of Gastroenterology  2004;10(10):1480-1486.
AIM: To detect the markers of oval cells in adult rat liver and to enrich them for further analysis of characterization in vitro.
METHODS: Rat model for hepatic oval cell proliferation was established with 2-acetylaminofluorene and two third partial hepatectomy (2-AAF/PH). Paraffin embedded rat liver sections from model (11 d after hepatectomy) and control groups were stained with HE and OV6, cytokeratin19 (CK19), albumin, alpha fetoprotein (AFP), connexin43, and c-kit antibodies by immunohistochemistry. Oval cell proliferation was measured with BrdU incorporation test. C-kit positive oval cells were enriched by using magnetic activated cell sorting (MACS) .The sorted oval cells were cultured in a low density to observe colony formation and to examine their characterization in vitro by immunocytochemistry and RT-PCR.
RESULTS: A 2-AAF/PH model was successfully established to activate the oval cell compartment in rat liver. BrdU incorporation test of oval cell was positive. The hepatic oval cells coexpressed oval cell specific marker OV6, hepatocyte-marker albumin and cholangiocyte-marker CK19. They also expressed AFP and connexin 43. C-kit, one hematopoietic stem cell receptor, was expressed in hepatic oval cells at high levels. By using c-kit antibody in conjunction with MACS, we developed a rapid oval cell isolation protocol. The sorted cells formed colony when cultured in vitro. Cells in the colony expressed albumin or CK19 or coexpressed both and BrdU incorporation test was positive. RT-PCR on colony showed expression of albumin and CK19 gene.
CONCLUSION: Hepatic oval cells in the 2-AAF/PH model had the properties of hepatic stem/progenitor cells. Using MACS, we established a method to isolate oval cells. The sorted hepatic oval cells can form colony in vitro which expresses different combinations of phenotypic markers and genes from both hepatocytes and cholangiocyte lineage.
PMCID: PMC4656289  PMID: 15133858

Results 1-13 (13)