(-)-Epigallocatechin-3-gallate plays an antagonistic role in the antitumor effect of bortezomib in myeloma cells via activating Wnt/ß-catenin signaling pathway.

BACKGROUND: (-)-Epigallocatechin-3-gallate (EGCG) is an active constituent of green tea, whose efficacy on chemoprevention and chemotherapy has been extensively researched. Its anticancer potency with low toxicity and easy administration allows for its widespread use. Bortezomib, a proteasome inhibitor, has a significant influence on multiple myeloma (MM) in chemotherapy. Previous studies about the role of EGCG in the antitumor effect induced by bortezomib remain controversial. OBJECTIVES: In our study, the effect of EGCG on the antitumor activity of bortezomib was investigated in myeloma cell lines U266 and RPMI8226, and the underlying mechanism was explored. MATERIAL AND METHODS: The effect of EGCG on the antiproliferative and pro-apoptotic activities of bortezomib were investigated in myeloma cells using MTT assay and cell cycle analysis, respectively. The Wnt/ß-catenin signaling pathway and related proteins were involved in this antagonistic effect and measured with western blot assay. RESULTS: Our results showed the inhibitory activity of EGCG on myeloma cells in a timeand dose-dependent manner. The EGCG neutralized the antiproliferative and pro-apoptotic effect induced by bortezomib by activating Wnt/ß-catenin signaling pathway with the accumulation of ß-catenin. An increase of the downstream target proteins as c-Myc and cyclin D1 was also observed. was also observed. These findings demonstrated the antagonistic role of EGCG in the antitumor effect of bortezomib likely through the activated Wnt/ß-catenin signaling pathway and the upregulated target proteins. CONCLUSIONS: When bortezomib is involved in the MM chemotherapy, the consumption of green tea should be avoided in order to maintain the biological efficacy of bortezomib.

HIV prevalence and incidence estimates among blood donors in five regions in China.

BACKGROUND: Previous data, although scant, indicated that the incidence of HIV in China has increased over the past decade. There is a growing concern about the impact of the HIV epidemic on blood safety. METHODS AND MATERIALS: We used donation data from five geographically-disperse blood centers in 2013-2016 participating in the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) China program to estimate HIV prevalence and incidence among blood donors. Multivariable logistic regression model was used to examine factors associated with HIV infection in Chinese blood donors. RESULTS: The overall HIV prevalence among first-time donors from 2013 through 2016 was 68.04 per 100,000 donors (95% CI 61.68-74.40). The HIV incidence rate was estimated to be 37.93 per 100,000 person-years (95% CI 30.62-46.97) among first-time donors and 20.55 per 100,000 person-years (95% CI 16.95-24.91) among repeat donors. There was substantial variation in HIV prevalence and incidence rates across blood centers. Multivariable logistic regression results showed that among first-time donors, being male, older than 25 years, minority ethnicity, less than college education, and certain occupations (commercial services, factory workers, retired, unemployed, or self-employed) were associated with positive HIV confirmatory testing results. CONCLUSION: HIV prevalence and incidence among blood donors remain low in the selected five regions in China; however, an increasing trend is observed at some blood centers. It is important to monitor HIV epidemiology in Chinese blood donors on a continuous basis, especially among populations and regions of higher risk.

Two Chinese Xia-Gibbs syndrome patients with partial growth hormone deficiency.

BACKGROUND: Heterozygous mutations in the AT-hook DNA-binding motif containing one (AHDC1, OMIM * 615790) gene cause an autosomal dominant multisystem developmental disorder known as Xia-Gibbs syndrome (OMIM #615829). Xia-Gibbs syndrome typically presented with global developmental delay, hypotonia, obstructive sleep apnea, seizures, delayed myelination, micrognathia, and other mild dysmorphic features. METHODS: Description of the clinical materials of two Chinese boys who were diagnosed with Xia-Gibbs syndrome based on clinical presentations and next generation sequencing. Review of clinical features and AHDC1 mutations in previously reported Xia-Gibbs syndrome patients together with our two new patients. RESULTS: The Xia-Gibbs syndrome patients exhibited short stature, hypotonia, global developmental delay, speech delay, simian crease, and mild dysmorphic features. Next generation sequencing revealed de novo heterozygous variants in AHDC1 gene. In addition, laboratory test revealed partial growth hormone deficiency. Both patients underwent growth hormone replacement therapy for 24 and 9 months, respectively, and exhibited good response to the treatment. CONCLUSION: This is the first report of Xia-Gibbs syndrome patients to be treated with growth hormone. Review of previously reported Xia-Gibbs syndrome patient indicated that short stature is a frequent feature of this condition, but its underlying cause needs to be further investigated.

The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014.

The increasing complexity and diversity of the human immunodeficiency virus-1 (HIV-1) infections challenge the disease control and anti-retrovirus treatment in China. The infection stages and molecular characteristics of HIV-1 from infected Chinese blood donors were examined to shed light on the HIV genotype distribution and the status of drug resistance mutations (DRMs) in the changing HIV epidemic in China. Western blot (WB) confirmed HIV-1 positive plasma samples were collected from blood donors at five Chinese blood centers from April 16, 2012, through June 30, 2014. The HIV infection stages were determined using the Lag-avidity assay. HIV Pol regions including whole protease and partial reverse transcriptase (RT) were amplified and sequenced to establish the profile of genotype distribution and drug resistance mutations (DRMs). Viral loads were determined using the ROCHE COBAS system. Of the 259 HIV-1 positive samples tested by the Lag-avidity assay, 23.6% (61/259) were identified as recent infections. A total of 205 amplified sequences displayed the following genotype distributions: circulating recombinant form (CRF) 07_BC (61.5%), CRF08_BC (8.3%), CRF01_AE (20%), B (6.3%), and 01B (3.9%). There was no significant difference in genotype distribution between recent and long-term infections. 31 DRMs were identified from 27 samples including four protease inhibitors (PIs) accessory DRMs, two PIs major DRMs (M46I), two nucleoside RT inhibitors DRMs (K219R and K70Q), and 23 nonnucleoside RT inhibitors DRMs. 27 samples had DRMs, yielding a drug resistance prevalence of 13.2% (27/205). Our findings provide important information for developing strategies for comprehensive HIV control and improving anti-retroviral treatment in China.

Risk factors for hepatitis B and C infection among blood donors in five Chinese blood centers.

BACKGROUND: Few studies were conducted on hepatitis B and C virus (HBV and HCV, respectively) risk factors among Chinese blood donors in recent years since voluntary donors replaced commercial donors. STUDY DESIGN AND METHODS: A case-control survey was conducted in HBV- or HCV-positive and -negative donors from five blood centers in China between September 2009 and April 2011. Case status was defined by having a reactive result on Monolisa HBsAg Ultra (Bio-Rad) for HBV and Ortho anti-HCV EIA 3.0 (Johnson & Johnson) for HCV. Controls were randomly selected qualified blood donors matched to cases by donation month and blood center. Specific test-seeking, medical-related, and behavioral risk factors were compared by HBV and HCV status using chi-square tests or Fisher's exact tests with Bonferroni correction. RESULTS: A total of 364 HBV cases, 174 HCV cases, and 689 controls completed the survey; response rates were 66.2, 47.3, and 82%, respectively. HCV-positive donors were significantly more likely to report having a blood transfusion history (23.4% vs. 3.0%, p < 0.0001) and ever living with a person with illegal drug injection (6.0% vs. 0.5%, p < 0.0001) than controls. Having intravenous and intramuscular injections in the past 12 months and ever having a tattoo are marginal risk factors for HCV (p values < 0.01). No specific risk factor for HBV was identified. CONCLUSION: History of previous transfusion and living with illegal drug users are risk factors for HCV infection among Chinese blood donors from five regions. Test-seeking behavior is not associated with HBV or HCV infections.

The persistence of hepatitis C virus transmission risk in China despite serologic screening of blood donations.

BACKGROUND: A total of 2%-2.9% of the population in China is infected with hepatitis C virus (HCV). This study estimated the prevalence and incidence of HCV among Chinese blood donors. STUDY DESIGN AND METHODS: We examined whole blood and apheresis platelet donations at five Chinese blood centers in 2008 to 2010. All donations were screened using two rounds of testing for alanine aminotransferase, antibody to human immunodeficiency virus Types 1 and 2, hepatitis B surface antigen, anti-HCV, and syphilis. Screening reactivity is defined by a reactive result in one or both rounds of screening tests. Confirmatory tests (Ortho third-generation HCV enzyme immunoassay, Johnson & Johnson) were performed on anti-HCV screening-reactive samples. Confirmatory positive rates among first-time donors (prevalence) and repeat donors (incidence) were calculated by blood center and demographic categories. Donor characteristics associated with HCV confirmatory status among first-time donors were examined using trend test and multivariable logistic regression analysis. RESULTS: Among 821,314 donations, 40% came from repeat donors. The overall anti-HCV screening-reactive rate was 0.48%. Estimated HCV prevalence was 235 per 100,000 first-time donors; incidence was 10 per 100,000 person-years in repeat donors. In multivariable logistic regression analysis, first-time donors older than 25 years displayed higher HCV prevalence than the younger donors. Less education is associated with higher HCV prevalence. Donors 26 to 35 years old and those above 45 years displayed the highest incidence rate. CONCLUSION: High prevalence and incidence in donors indicate high residual risks for transfusion-transmitted HCV in Chinese patients. Implementation of minipool nucleic acid testing in routine donation screening may prevent a substantial number of transfusion-transmitted HCV infections.

Long-term return behavior of Chinese whole blood donors.

BACKGROUND: It is important to understand donor return behavior to maintain sufficient numbers of blood donors in developing countries where blood supplies are often inadequate. STUDY DESIGN AND METHODS: A total of 54,267 whole blood (WB) donors who donated between January 1 and March 31, 2008, at the five blood centers in China were followed for 2.5 years. Logistic regression was conducted to identify factors associated with their return behavior. A recurrent-event Cox proportional-hazard model was used to evaluate the overall effect of demographic variables and return behavior among first-time donors. RESULTS: Donors with previous donation history were more likely to return and the number of previous returns was positively associated with future return (odds ratios, 3.31, 4.82, and 8.16 for one, two to three, and more than three times compared to none). Thirty-four percent of donors (first-time donor, 21%; repeat donor, 54%) made at least one return donation, with 14% returning in the first 9 months. The multivariable logistic regression model for all WB donors and the Cox proportional hazard model for first-time donors showed consistent predictors for return: female sex, older age (≥ 25 years), larger volume (300 or 400 mL), and donating in satellite collection site. CONCLUSION: Encouraging first-time donors to make multiple donations is important for keeping adequate blood supply. The finding that first-time and repeat donors shared the same predictors for return indicates that retention strategies on repeat donors may be effective on first-time donors. Studies on motivators and barriers to return are needed, so that successful retention strategies can be tailored.

Demographics of apheresis platelet donors in five blood centers in China.

BACKGROUND: Blood component donations by apheresis has become more common in modern blood transfusion practices. However, apheresis donation still remains less common in China. This study describes the demographic profile and transfusion-transmissible infection (TTI) prevalence among donors making apheresis platelet (AP) donations compared to those making whole blood (WB) donations and the differences among five geographically diverse blood centers in China. STUDY DESIGN AND METHODS: This is a descriptive study using data from all successful donations at the five blood centers in 2008 and 2009. Donor demographic and TTI screening reactive rates were collected for WB and AP donations and blood centers. Logistic regression was used to identify independent factors associated with AP donations. RESULTS: From January 1, 2008, to December 31, 2009, there were 512,594 WB and 26,199 AP donations at five blood centers. AP donations accounted for 4.9% of all donations. AP donations have lower reactive rate than WB donations for hepatitis B virus surface antigen, hepatitis C virus antibodies, human immunodeficiency virus antibodies, and syphilis screening testing. Males, donors older than 25 years old, non-Han donors, and donors with below high school educational level were more likely to make AP donations. The characteristics of AP donations differed among the five Chinese blood centers. CONCLUSION: Our analysis suggests that the characteristics of AP donations in China are different from WB donations and differ among the five Chinese blood centers. Some of the differences are likely due to different recruitment policies. Further studies should be conducted to understand what motivates Chinese blood donors to participate as AP donors.

Analysis of Chinese donors' return behavior.

BACKGROUND: It is important to understand donor return behavior. Converting first-time donors to become repeat donors is essential for maintaining an adequate blood supply. STUDY DESIGN AND METHODS: Characteristics of 241,552 whole blood (WB) donations from first-time and repeat donors who donated in 2008 at the five blood centers in China were compared. A subset of 54,394 WB donors who donated between January 1 and March 31, 2008, were analyzed for their return behavior in 2008 after the index donation using logistic regression. RESULTS: Of all donations, 64% were from first-time donors. Donors with self-reported previous donations tended to be male, older, and married; donated larger volume (≥ 300 mL); and were heavier in weight. Among donors who donated from January to March 2008, 14% returned for subsequent WB donations by the end of 2008. The number of previous donations and blood collection location were the two strongest predictors for making subsequent donations. Donors with one, two to three, and more than three previous donations were 3.7, 5.7, and 11.0 times more likely to return than first-time donors. Those who donated in a blood collection vehicle were four times more likely to return than those who donated at a blood center. Being female, younger, and of a lower education level (middle school or less) were positively associated with subsequent return blood donation during the follow-up period observed in this study. CONCLUSION: Most of the Chinese blood supply is from first-time donors. Strategies aimed at encouraging current donors to become repeat donors are needed.

Impact of the May 12, 2008, Earthquake on blood donations across five Chinese blood centers.

BACKGROUND: On May 12, 2008, a severe earthquake struck China's Sichuan Province. The nationwide outpouring of charity resulted in a surge of subsequent blood donations. The quantity and quality of these donations were examined in comparison with routine donations. STUDY DESIGN AND METHODS: Whole blood and apheresis donations from five geographically different blood centers collected within 1 week postearthquake were compared with those collected during the rest of the year. Regional differences, demographic characteristics, first-time and repeat donor status, and infectious disease screening markers associated with these donations were compared by earthquake status using chi-square statistics. Poisson regression analysis examined the number of daily donations by earthquake status after adjusting for center, day of week, and seasonal variations. RESULTS: The number of daily donations across five blood centers increased from 685 on a typical day to 1151 in the postearthquake week. The surge was observed in both sexes and across different education levels, age, and ethnicity groups and three blood centers and was significant after adjusting for confounding covariates. The influx of first-time donors (89.5%) was higher than that of repeat donors (34%). There was a significant change in the overall screening reactive marker rates excluding alanine aminotransferase (2.06% vs. 1.72%% vs. 4.96%). However, when the individual screening test was analyzed separately, no significant differences were found. CONCLUSION: Timely donations in response to a disaster are crucial to ensure emergency blood transfusion. The dramatically increased postearthquake donations suggest that Chinese blood centers are capable of handling emergency blood needs. Measures to maintain blood safety should be taken in times of emergency.