We followed 145 men with chronic hepatitis B virus (HBV) hepatitis for 10 years to determine whether exposure to aflatoxin, or concomitant exposure to hepatitis C virus (HCV), or family history of hepatocellular carcinoma (HCC) increased the risk of developing HCC. We collected 8 monthly urine samples before beginning follow-up and pooled them to detect aflatoxin metabolite M1 (AFM1). AFM1 was detected in 78 (54%) of the subjects. The risk of HCC was increased 3.3-fold (with a 95% confidence interval of 1.2-8.7) in those with detectable AFM1 (above 3.6 ng/L). This relative risk was adjusted for age and for HCV status. Hepatocellular carcinoma (HCC) is the second most common cause of death from cancer in China, where the mortality rate was 18 per 100,000 person-years in 1990 through 1992. 1 Infection with hepatitis B virus (HBV) and exposure to aflatoxin are both important risk factors for HCC. Ross et al. 2 studied 18,244 men aged 45 to 64 who lived in Shanghai between 1986 and 1989. In a sample of 140 controls who were age-matched to HCC cases, it was found that 15 (11%) were hepatitis B surface antigen (HBsAg)-positive, and 53 (38%) had detectable urinary aflatoxin metabolites or DNAadducts. A later analysis of 50 HCC cases and 267 agematched controls from this study 3 showed that compared with men without HBsAg or urinary aflatoxin biomarkers, relative risks were 7.3 with 95% a confidence interval (2.2, 24) for those only with HBsAg, 3.4 (1.1, 10) for those only with aflatoxin biomarkers, and 59 (17, 212) for those with both. Based on such data, Ross et al. 2 and Qian et al. 3 suggested that reduction of exposure to aflatoxin might prevent a considerable fraction of the HCC in this population.The previous cohort represented the general male population of Shanghai. We chose instead to follow prospectively a representative group of 145 carriers of HBsAg with a history of chronic hepatitis. These men were being cared for at the Medical Oncology Department of the Qidong Liver Cancer Institute/Hospital, Qidong, Jiangsu Province, China. HCC rates are very high in Qidong. The purpose of the study was to determine whether exposure to aflatoxin increased the risk of HCC or of fatal cirrhosis over a 10-year period in patients with HBV hepatitis. A positive finding would suggest that measures to reduce exposure to aflatoxin might also be beneficial to men with chronic HBV hepatitis and could be evaluated in treatment protocols. Because we collected monthly urine samples for 8 months before beginning follow-up, we were able to pool the samples to obtain estimates of long-term average urinary aflatoxin M1 (AFM1) concentrations, and the assay could detect concentrations of AFM1 as low as 3.6 ng/L. These data also give information on the added risks of HCC in men with chronic HBV hepatitis from exposure to hepatitis C virus (HCV) and from a family history of HCC. PATIENTS AND METHODSPopulation-based sampling was used to obtain a representative study cohort. In an earlier study of the prevalence of HBV infection sponsored by...

We assessed the separate and combined effects of hepatitis B virus (HBV), hepatitis C virus (HCV), and aflatoxin in causing hepatocellular carcinoma (HCC) in Qidong, China. A consecutive series of 181 pathologic-diagnosed HCC cases were studied for hepatitis B surface antigen (HBsAg), anti-HBc, HBV X gene sequence, anti-HCV, the 249ser-p53 mutation, and chronic hepatitis pathology. Each of the 181 incident HCC cases had markers for HBV infection and hepatitis pathology; only 6 of 119 cases were coinfected with HCV. The 249ser-p53 mutation was found in 54% (97/181) of HCC cases and in all 7 cases with tissue for analysis from the hepatitis cohort but in none of 42 matched cases from Beijing. The estimated cumulative dose of aflatoxin B1 in these 7 cases ranged from 0.13 to 0.49 mg/kg. Follow-up data through 13.25 years on a cohort of 145 men with chronic HBV hepatitis showed that the relative risk from aflatoxin exposure was 3.5 (1.5-8.1). A similar relative risk was found using 249ser-p53 mutation as a marker for aflatoxin exposure. In conclusion, HBV hepatitis is ubiquitous in Qidong HCC cases, whereas HCV contributes little to its risk. The 249ser-p53 mutation appears to result from coexposure to aflatoxin and HBV infection. Even modest levels of aflatoxin exposure tripled the risk of HCC in HBV-infected men. H epatocellular carcinoma (HCC) is the second most common cancer and kills 300,000 or more people each year in China. 1,2 The close linkage of hepatitis B virus (HBV) to HCC was largely established in epidemiologic studies based on the detection of HBV surface antigen (HBsAg) in sera. In Qidong, China, about 16% of the adult population are seropositive for HBsAg. This marker is not present in every person infected with HBV, however. Early studies had shown that many HBsAg seronegative HCC patients in Qidong had evidence of HBV infection determined by immunohistochemistry 3 or by molecular hybridization in European cases. 4 Fujimoto et al. 5 reported that 23 of 26 HCC cases from Qidong were HBV positive by Southern blot analysis, including 3 HBsAg seronegatives. Paterlini et al. 6 had shown by reverse transcriptase polymerase chain reaction assays that HBV X gene-related transcripts were often found in the diseased and normal hepatic tissues of HBsAg-negative HCC patients. In Japan, many HCC cases attributed to hepatitis C virus (HCV) were found to have markers of HBV infection. 7-9 Zhang et al. 10 reported that PCR analysis of 21 HBsAg seronegative HCC cases in Qidong revealed HBV X gene sequence in the HCC DNA of every case. A recent cohort study in Qidong also showed that HBV worked synergistically with aflatoxin, HCV, and family history to significantly enhance HCC incidence. 11 Using an extensive set of assays, we sought to determine whether HBV infection is virtually ubiquitous in HCC cases in Qidong. Such a finding would have implications for understanding the carcinogenic process

The epidemiology of candidaemia varies between hospitals and geographic regions. Although there are many studies from Asia, a large-scale cross-sectional study across Asia has not been performed. We conducted a 12-month, laboratory-based surveillance of candidaemia at 25 hospitals from China, Hong Kong, India, Singapore, Taiwan and Thailand. The incidence and species distribution of candidaemia were determined. There were 1601 episodes of candidaemia among 1.2 million discharges. The overall incidence was 1.22 episodes per 1000 discharges and varied among the hospitals (range 0.16-4.53 per 1000 discharges) and countries (range 0.25-2.93 per 1000 discharges). The number of Candida blood isolates and the total number of fungal isolates were highly correlated among the six countries (R² = 0.87) and 25 hospitals (R² = 0.77). There was a moderate correlation between incidence of candidaemia and the intensive care unit (ICU)/total bed ratio (R² = 0.47), although ICUs contributed to only 23% of candidaemia cases. Of 1910 blood isolates evaluated, Candida albicans was most frequently isolated (41.3%), followed by Candida tropicalis (25.4%), Candida glabrata (13.9%) and Candida parapsilosis (12.1%). The proportion of C. tropicalis among blood isolates was higher in haemato-oncology wards than others wards (33.7% versus 24.5%, p 0.0058) and was more likely to be isolated from tropical countries than other Asian countries (46.2% versus 18.9%, p 0.04). In conclusion, the ICU settings contribute, at least in part, to the incidence variation among hospitals. The species distribution is different from Western countries. Both geographic and healthcare factors contribute to the variation of species distribution.

Qidong City, China, has had high liver cancer incidence from endemic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin. Based on etiologic studies, we began interventions in 1980 to reduce dietary aflatoxin and initiate neonatal HBV vaccination. We studied trends in liver cancer incidence rates in the 1.1 million inhabitants of Qidong and examined trends in aflatoxin exposure, staple food consumption, HBV infection markers and annual income. Aflatoxin exposure declined greatly in association with economic reform, increased earnings and educational programs to shift staple food consumption in the total population from moldy corn to fresh rice. A controlled neonatal HBV vaccination trial began in 1983 and ended in November, 1990, when vaccination was expanded to all newborns. Liver cancer incidence fell dramatically in young adults. Compared with 1980-83, the age-specific liver cancer incidence rates in 2005-08 significantly decreased 14-fold at ages 20-24, 9-fold at ages 25-29, 4-fold at ages 30-34, 1.5-fold at ages 35-39, 1.2-fold at ages 40-44 and 1.4-fold at ages 45-49, but increased at older ages. The 14-fold reduction at ages 20-24 might reflect the combined effects of reduced aflatoxin exposure and partial neonatal HBV vaccination. Decrease incidence in age groups >25 years could mainly be attributable to rapid aflatoxin reduction. Compared with 1980-83, liver cancer incidence in 1990-93 significantly decreased 3.4-fold at ages 20-24, and 1.9-fold at ages 25-29 when the first vaccinees were <11 years old.

Either G-2964 or A734 in the human CYP1A2 gene was confirmed to be associated with high inducible enzyme activity in smokers, but not in nonsmokers. In this study, for the first time, we observed an association between phenotypes and genotypes of CYP1A2 with respect to the two genetic polymorphisms in 163 healthy Chinese volunteers living in Qidong. The ratio of plasma 17X/137X at 6 h after oral administration of 300 mg caffeine was employed in CYP1A2 phenotyping analysis, while genotyping analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism. The allele frequencies of A at -2964 and A at 734 in 139 non-smoking subjects were 0.25 and 0.67, respectively. The A/A-2964C/C734, G/A-2964C/C734 or A/A-2964C/A734 genotype that was thought to have lower inducibility/activity of CYP1A2 than the other genotypes did not exist in the tested Chinese subjects. The ratio of 17X/137X was 0.46 +/- 0.26 in G/G-2964A/A734 genotypes (n = 22) and 0.36 +/- 0.19 in non-G/G-2964A/A734 (n = 117). In addition, there was significant difference between them (P = 0.036). A similar result was also achieved in 24 smokers. Since Qidong is a special region with particularly high incidence of hepatocellular carcinoma in China, the association of phenotypes with genotypes of CYP1A2 in the Qidong population might result from some inducible environmental factors such as those of cigarettes in smokers.

Breast cancer stem cells (BCSCs) contribute to intra-tumoral heterogeneity and therapeutic resistance. However, the binary concept of universal BCSCs co-existing with bulk tumor cells is over-simplified. Through single-cell RNA-sequencing, we found that Neu, PyMT and BRCA1-null mammary tumors each corresponded to a spectrum of minimally overlapping cell differentiation states without a universal BCSC population. Instead, our analyses revealed that these tumors contained distinct lineage-specific tumor propagating cells (TPCs) and this is reflective of the self-sustaining capabilities of lineage-specific stem/progenitor cells in the mammary epithelial hierarchy. By understanding the respective tumor hierarchies, we were able to identify CD14 as a TPC marker in the Neu tumor. Additionally, single-cell breast cancer subtype stratification revealed the co-existence of multiple breast cancer subtypes within tumors. Collectively, our findings emphasize the need to account for lineage-specific TPCs and the hierarchical composition within breast tumors, as these heterogenous sub-populations can have differential therapeutic susceptibilities.

Glycine is a simple nonessential amino acid known to have neuroprotective properties. Treatment with glycine results in reduced infarct volume of the brain, neurologic function scores, and neuronal and microglial death in ischemic stroke injury. Neuroinflammation has been considered a major contributor to cerebral ischemia–induced brain damage. However, the role of glycine in neuroinflammation following ischemic stroke is unclear. The present study aimed to determine whether neuroinflammation is involved in the neuroprotective effects of glycine in cerebral ischemia injury. Ischemic stroke promotes M1 microglial polarization. Interestingly, we found that the injection of glycine in rats after injury can inhibit ischemia-induced inflammation and promote M2 microglial polarization in vivo (Sprague–Dawley rats) and in vitro (cortical microglia and BV-2 cells). We show that glycine suppresses Hif-1α by inhibiting the upregulation of NF-κB p65 after ischemia-reperfusion injury, resulting in the inhibition of proinflammatory activity. The activation of AKT mediates the inhibition of NF-κB p65/Hif-1α signaling by glycine. Moreover, we confirm that glycine-regulated AKT activation is mediated by the inhibition of PTEN in a PTEN depletion cell line, U251 cells. Glycine modulates microglial polarization after ischemic stroke, which indirectly inhibits ischemia-induced neuronal death and functional recovery. Taken together, our findings provide a new understanding of glycine in neuroprotection by inhibiting M1 microglial polarization and promoting anti-inflammation by suppressing NF-κB p65/Hif-1α signaling.

The outbreak and worldwide spread of COVID-19 has resulted in a high prevalence of mental health problems in China and other countries. This was a cross-sectional study conducted using an online survey and face-to-face interviews to assess mental health problems and the associated factors among Chinese citizens with income losses exposed to COVID-19. The degrees of the depression, anxiety, insomnia, and distress symptoms of our participants were assessed using the Chinese versions of the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7), the Insomnia Severity Index-7 (ISI-7), and the revised 7-item Impact of Event Scale (IES-7) scales, respectively, which found that the prevalence rates of depression, anxiety, insomnia, and distress caused by COVID-19 were 45.5%, 49.5%, 30.9%, and 68.1%, respectively. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes among workers with income losses during COVID-19. Participants working in Hubei province with heavy income losses, especially pregnant women, were found to have a high risk of developing unfavorable mental health symptoms and may need psychological support or interventions.