Hepatoma-derived growth factor participates in concanavalin A-induced hepatitis.

Hepatitis is an important health problem worldwide. Novel molecular targets are in demand for detection and management of hepatitis. Hepatoma-derived growth factor (HDGF) has been delineated to participate in hepatic fibrosis and liver carcinogenesis. However, the relationship between hepatitis and HDGF remains unclear. This study aimed to elucidate the role of HDGF during hepatitis using concanavalin A (ConA)-induced hepatitis model. In cultured hepatocytes, ConA treatment-elicited HDGF upregulation at transcriptional level and promoted HDGF secretion while reducing intracellular HDGF protein level and cellular viability. Similarly, mice receiving ConA administration exhibited reduced hepatic HDGF expression and elevated circulating HDGF level, which was positively correlated with serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. By using HDGF knockout (KO) mice, it was found the ConA-evoked cell death was prominently alleviated in KO compared with control. Besides, it was delineated HDGF ablation conferred protection by suppressing the ConA-induced neutrophils recruitment in livers. Above all, the ConA-mediated activation of tumor necrosis factor-α (TNF-α)/interleukin-1ß (IL-1ß)/interleukin-6 (IL-6)/cyclooxygenase-2 (COX-2) inflammatory signaling was significantly abrogated in KO mice. Treatment with recombinant HDGF (rHDGF) dose-dependently stimulated the expression of TNF-α/IL-1ß/IL-6/COX-2 in hepatocytes, further supporting the pro-inflammatory function of HDGF. Finally, application of HDGF antibody not only attenuated the ConA-mediated inflammatory cascade in hepatocytes, but also ameliorated the ConA-induced hepatic necrosis and AST elevation in mice. In summary, HDGF participates in ConA-induced hepatitis via neutrophils recruitment and may constitute a therapeutic target for acute hepatitis.

Association analyses of apolipoprotein E genotypes and cognitive performance in patients with Parkinson's disease.

BACKGROUND: Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. METHODS: A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson's Progression Marker Initiative (PPMI). RESULTS: No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aß42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. CONCLUSIONS: APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aß42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.

Effect of Conventional and "Dental Truth or Dare" Board Game on Oral Hygiene Knowledge and Oral Hygiene Status of Preschool Children.

Aim: To compare the benefits of didactic versus board game-based oral health instruction on oral health knowledge (OHK) and oral hygiene of preschool students. Materials and Methods: Participants were selected through computer-assisted randomization. (Eighty students were selected in both the 3- to 4-year-old and 5- to 6-year-old age groups, respectively, for a total of 160 participants). Forty participants of each age group were assigned randomly to Group A (PowerPoint® presentation) and 40 to Group B ("Dental Truth or Dare" board game-based instruction). OHK and debris index-simplified (DI-S) were assessed at preintervention, and at 1-week, 1-month, and 3-month postintervention timepoints. Results: OHK scores increased significantly in the 3- to 4-year-old subset of Group A at the 1-week postintervention timepoint but declined and approximated the baseline value at the 3-month timepoint. In contrast, compared to baseline, significantly improved OHK scores were observed at all 3 timepoints in both age groups in Group B, and were especially pronounced in the 5- to 6-year-old subset. Although the 3-month scores were slightly lower than the 1-week scores, they were well above baseline values. Pre- and postintervention DI-S scores did not change significantly in the 3- to 4-year-old subset of Group A. However, significant increases in good DI-S scores and decreases in fair and poor scores were observed between baseline and 3-month timepoints in the 5- to 6-year-old subset of Group A and in both age subsets of Group B (P ≤ 0.05). OHK and DI-S scores were significantly higher among 5-6-year-olds than among the 3-4-year olds in both Groups A and B (P ≤ 0.05). Age and board game intervention were the main determinants of higher OHK and lower DI-S scores. The impact of intervention mode (board game) was greater than that of age. Conclusion: Board game-based oral hygiene education conferred significant short-term retention, enhanced OHK, and reduced DI-S. We conclude that gaming is an easily implemented and cost-effective educational tool for the improvement of oral hygiene in preschool children.

Prevalence of and risk factors for hepatitis C virus infection among blood donors in Chengdu, China.

The objectives of the study were to estimate the prevalence of anti-hepatitis C virus (HCV) positivity among blood donors from Chengdu, China, and to determine risk factors associated with infection. In this study, data were collected from volunteer blood donors between July 2006 and June 2007. Anti-HCV test was performed in 119,518 donors. To identify risk factors associated with HCV infections a case-control study was conducted in 305 unique HCV-seropositive blood donors and 610 seronegative donors matched for age and sex. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. The population attributable risk (PAR) to risk factor was estimated according to the Bruzzi's formula. The prevalence of anti-HCV positivity was 0.53% (95% CI: 0.489-0.572%). The final multivariate model included the following independent HCV risk factors: razor sharing (OR=29.16; 95% CI: 12.89-66.00), blood transfusion (OR=20.84; 95% CI: 3.76-115.45), acupuncture (OR=8.01; 95% CI: 3.16-20.30), a history of hospitalization, injections >10 years earlier, a family history of hepatitis B, dental treatment, and ear piercing. The PAR of risk factors are 68.4%, 6.3%, 14.1%, 23.1%, 29.5%, 29.3%, 38.9%, and 27.8%, respectively, and the total PAR is 98.3%. Infection with HCV among blood donors in Chengdu is associated with iatrogenic risk factors and beauty treatment-related risk. Razor sharing is an important risk factor for HCV infection. These results indicate that infection control measures in healthcare settings may reduce the burden of HCV infection and there is a need for development of effective educational programs to improve HCV knowledge among beauty culture professionals, barber cosmetologists, and the general public to avoid risk behaviors.

[Expression of phosphatase and tensin homolog in lower rectal cancer on neoadjuvant chemoradiotherapy].

OBJECTIVE: To explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in low rectal cancer on neoadjuvant chemoradiotherapy with capecitabine plus radiotherapy. METHODS: Sixty-six patients with low rectal cancer on therapy with capecitabine (1650 mg×m(-2)×d(-1) in 2 divided doses) for two course and concurrent radiotherapy (50 Gy, 2 Gy/day, 5 days a week). Then the investigators analyzed the relationship between the preoperative neoadjuvant chemoradiotherapy and prognosis and measured the expression of PTEN during neoadjuvant chemoradiotherapy. RESULTS: 92.4% (61/66) of patients received neoadjuvant chemoradiotherapy as planned. 87.9% (58/66) tumor stages were down-staged, tumor size decreased while the distance from anal edge increased. And curative resection with sphincter-sparing was carried out in all patients. The rate of sphincter preservation was 90.9% (60/66). Among which, 85.5% patients showed an excellent function of sphincter. The 2-year survival rate was 87.9% (58/66). The survival period was an average of 35.3 months (range: 25-60). The PTEN mRNA and protein expression in cancer tissues on neoadjuvant chemoradiotherapy were significantly higher than those before neoadjuvant chemoradiotherapy (P=0.0079, 0.0269). CONCLUSIONS: The preoperative neoadjuvant chemoradiotherapy in lower rectal cancer patients has shown its efficacy in down-staging cancer, enhancing resectability, offering sphincter preservation, up-regulating PTEN expression, promoting the apoptosis of cancer cell and achieving a better survival rate. Thus preoperative neoadjuvant chemoradiotherapy is an effective adjuvant measure.

Irisin Mitigates Oxidative Stress, Chondrocyte Dysfunction and Osteoarthritis Development through Regulating Mitochondrial Integrity and Autophagy.

Compromised autophagy and mitochondrial dysfunction downregulate chondrocytic activity, accelerating the development of osteoarthritis (OA). Irisin, a cleaved form of fibronectin type III domain containing 5 (FNDC5), regulates bone turnover and muscle homeostasis. Little is known about the effect of Irisin on chondrocytes and the development of osteoarthritis. This study revealed that human osteoarthritic articular chondrocytes express decreased level of FNDC5 and autophagosome marker LC3-II but upregulated levels of oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG) and apoptosis. Intra-articular administration of Irisin further alleviated symptoms of medial meniscus destabilization, like cartilage erosion and synovitis, while improved the gait profiles of the injured legs. Irisin treatment upregulated autophagy, 8-OHdG and apoptosis in chondrocytes of the injured cartilage. In vitro, Irisin improved IL-1ß-mediated growth inhibition, loss of specific cartilage markers and glycosaminoglycan production by chondrocytes. Irisin also reversed Sirt3 and UCP-1 pathways, thereby improving mitochondrial membrane potential, ATP production, and catalase to attenuated IL-1ß-mediated reactive oxygen radical production, mitochondrial fusion, mitophagy, and autophagosome formation. Taken together, FNDC5 loss in chondrocytes is correlated with human knee OA. Irisin repressed inflammation-mediated oxidative stress and extracellular matrix underproduction through retaining mitochondrial biogenesis, dynamics and autophagic program. Our analyses shed new light on the chondroprotective actions of this myokine, and highlight the remedial effects of Irisin on OA development.

Pembrolizumab for recurrent/metastatic head and neck squamous cell carcinoma in an Asian population.

Head and neck squamous cell carcinoma (HNSCC) has a high prevalence and is a major cause of cancer deaths in Taiwan. However, there is still no effective salvage therapy that prolongs the life expectancy of patients with recurrent/metastatic (R/M) HNSCC. Immune checkpoint therapy that targets the programmed cell death protein 1 (PD-1) may provide clinical benefit for these patients. We analyzed 22 R/M HNSCC patients who received pembrolizumab, a monoclonal antibody against PD-1, as salvage therapy. Intravenous pembrolizumab was given at a fixed dosage of 100 or 200 mg every 3 weeks. Three patients also received local palliative radiotherapy, but no patients received chemotherapy or targeted drugs. Seventeen patients (77.3%) received at least 3 cycles of pembrolizumab. Based on Response Evaluation Criteria in Solid Tumors criteria (ver. 1.1), 2 patients (9.1%) had complete response, 5 (22.7%) had partial response, and 6 (27.3%) had stable disease, corresponding to a disease control rate of 59.1%. Four patients had confirmed disease progression, 2 of whom had continuous progression over the target lesion after shrinkage of other metastases. One patient developed immune-related pneumonitis that resolved quickly after steroid treatment. Another patient developed itchy skin rashes immediately after administration of pembrolizumab, and this was controlled by an antihistamine. There were no other severe adverse effects. Pembrolizumab is beneficial and well-tolerated for some patients with refractory R/M HNSCC. However, it is important to identify biomarkers to identify the most responsive patients when designing future trials.

Pathologic response during chemo-radiotherapy and variation of serum VEGF levels could predict effects of chemo-radiotherapy in patients with esophageal cancer.

BACKGROUND: To investigate the relationship between pathologic tumor response to concurrent chemo- radiotherapy and variation of serum VEGF in patients with esophageal cancer. MATERIALS AND METHODS: Forty six patients with esophageal cancer who were treated with concurrent chemo-radiotherapy were enrolled. Endoscopic and pathologic examination was conducted before and four weeks afterwards. Serum level of VEGF was documented before, four weeks later and after chemo-radiotherapy. The relationship between pathologic response and the variation of serum level of VEGF and its influence on the prognosis were investigated. RESULTS: Serum level of VEGF decreased remarkably during and after chemo-radiotherapy in patients whose pathologic response was severe (F=5.393, 4.587, P(0.05). There were no statistical differences of serum VEGF level before, during and after chemo-radiotherapy for patients whose pathologic response was moderate or mild. There were 18 (85.7%), 7 (53.8%) and 6 patients (50.0%) whose serum VEGF level dropped in the severe, moderate and mild group, respectively, with significant differences among these groups (p=0.046). Two year survival rates of patients with severe, moderate and mild pathologic response were 61.9%, 53.8% and 33.3% respectively, and no statistically difference between severe and mild group regarding OS (p=0.245) was tested. CONCLUSIONS: Tumor pathologic response during chemo-radiotherapy and the changes of serum VEGF lever could predict curative effects of chemo-radiotherapy in patients with esophageal cancer.

[Effect of gap size between tooth and restorative materials on microbiolism based caries in vitro].

OBJECTIVE: To evaluate the effect of gap size between tooth and restorative materials on microbiolism based caries in vitro. METHODS: Tooth blocks made of human molars without caries and the same size composite resin blocks were selected and prepared. Tooth-resin matrix was mounted on resin base with a gap size of 0, 25, 50, 100, 190, 250 µm and a control group was dealed with adhesive system. Six experimental groups and one control group were included, with 8 samples in one group and a total of 56 samples. The samples were cultured by a 14-day sequential batch culture technique. The development of outer surface lesion and wall lesion was assessed with confocal laser scanning microscope (CLSM) by measuring the maximum lesion depth, fluorescence areas and average fluorescence value. The data were collected and statistically analyzed. The deposits of the tooth-restoration interface and the development of the carious lesion were observed by scanning electron microscope (SEM). RESULTS: Most groups showed outer surface lesion and wall surface lesions observed by CLSM and SEM except 2 samples in control group. There was no significant difference on the outer surface lesion (P > 0.05). The maximum lesion depth [(1145.37 ± 198.98), (1190.12 ± 290.80) µm respectively], the maximum lesion length, fluorescence areas and average fluorescence value of 190 and 250 µm groups' wall lesions were significantly higher than the 0, 25, 50 and 100 µm groups [the maximum lesion depth was (205.25 ± 122.61), (303.87 ± 118.80), (437.75 ± 154.88), (602.87 ± 269.13) µm respectively], P < 0.01. With the increase of the gap size, the demineralization developed more seriously. While the maximum lesion depth, the maximum lesion length and fluorescence areas of 0, 25, 50 µm groups' wall lesions were of no significant difference. CONCLUSIONS: There was close relationship between gap size and wall lesion when the gap was above 100 µm at tooth-composite resin interface. The existence of gap was the main influencing factor on the development of microbiolism based caries lesion.

[Relationship of gallstone formation after radical gastrectomy with the polymorphisms of apolipoprotein B Xba I and lipoprotein lipase Hind III gene].

OBJECTIVE: To investigate the relationship of gallstone formation after radical gastrectomy with the polymorphisms of apolipoprotein B (ApoB) Xba I gene and lipoprotein lipase (LPL) Hind III gene. METHODS: A total of 80 gastric cancer patients who underwent radical gastrectomy at our hospital between January 2006 and December 2006 were divided into different groups according to the polymorphisms of ApoB Xba I gene and LPL Hind III gene. The gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism. Gallstone formation 2 years after radical gastrectomy was compared among different genotype groups. RESULTS: Eight patients were lost to follow-up. According to the genotype detection, 72 patients were divided into X(+)X(-) group (10 cases), X(-)X(-) group (62 cases), H(-) group (27 cases) and H(-) deletion group (45 cases). The incidence of gallstone was significantly higher in X(+)X(-) group than that in X(-)X(-) group (60.0% vs 6.5%, P<0.01). The serum levels of total cholesterol TC and low density lipoprotein were significantly higher in X(+)X(-) group than those in X(-)X(-) group (P<0.05), but the level of ApoB was not significantly different between the two groups. The incidence of gallstone was not significantly different between H(-) group and H(-) deletion group (14.8% vs 13.3%). The level of triglyceride in H(-) group was significantly lower than that in H(-) deletion group before operation, however the difference disappeared after operation. CONCLUSION: X(+) allele may be associated with gallstone formation after radical gastrectomy, while H(-) may not.

XbaI polymorphisms of apolipoprotein B gene: another risk factor of gallstone formation after radical gastrectomy.

AIM: To prospectively investigate the association between the XbaI polymorphisms of apolipoprotein B (APOB) gene and gallstone formation following gastrectomy. METHODS: The study was conducted between January 2005 and December 2006. A total of 186 gastric cancer patients who had undergone radical gastrectomy were grouped according to XbaI polymorphisms of APOB gene (X(+)X(-) group, n = 24 and X(-)X(-) group, n = 162) and compared. The XbaI polymorphisms of APOB gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The incidence of gallstone was significantly higher in the X(+)X(-) group than in the X(-)X(-) group [54.2% vs 9.3%, RR = 5.85 (2.23-15.32), P < 0.001]. The serum levels of total cholesterol (TC) and low-density lipoprotein (LDL) were higher in the X(+)X(-) than in the X(-)X(-) group (4.02 +/- 1.12 vs 3.48 +/- 0.88, P = 0.004 before surgery and 3.88 +/- 1.09 vs 3.40 +/- 0.86, P = 0.008 after surgery). LDL was 2.21 +/- 0.96 vs 1.89 +/- 0.84 (P = 0.042) before surgery and 2.09 +/- 0.95 vs 1.72 +/- 0.85 (P = 0.029) after surgery in the two groups. No relationship was found between XbaI polymorphisms and gallbladder motility. CONCLUSION: In Chinese patients after radical gastrectomy, X(+) allele of APOB gene is another risk factor for the development of gallstone besides the gallbladder motility disorder after surgery.

[Expression of RhD antigen on RBC of different RhD serotype by flow cytometry].

This study was purposed to establish the method of quantifying RhD antigen on red blood cells (RBC) by flow cytometry (FCM) and to explore the expression of D antigen on RBC of different RhD serotype. RhD(+) RBCs and RhD(-) RBCs were mixed in 1:1 ratio. Cells were stained by the indirect method (IgG anti-D as the first antibody, FITC-anti-IgG F(ab')2 as the second antibody), and the ratio of RhD(+) on RBCs was quantified by FCM. The optimal dosage of IgG anti-D was defined. Expression of RhD antigen on RBC of RhD(+), weak D, RhDel and RhD(-) type were detected by FCM. The results showed that optimal dilution of IgG anti-D monoclonal antibody was 1:4, 1x10(6) cells/50 microl. The percentage of D(+) RBC of RhD(+), weak D, RhDel and RhD(-) type were 96.8+/-2.97%, 79.5+/-9.88%, 47.8+/-11.43%, 3.7+/-2.96%, respectively. The mean fluorescence intensity (MFI) of RhD antigen expression of RhD(+), weak D, RhDel and RhD(-) type were 33.3+/-6.21 Dal, 18.6+/-5.39 Dal, 7.10+/-1.17 Dal, 0.79+/-0.55 Dal, respectively. In conclusion, there are significant differences of RhD antigen expressions among RBC of different RhD serotypes. The level of antigen on RhD(+) RBC is the highest and then weak D the next, while the level of antigen on RhDel RBC is the lowest level.