Current therapies to treat advanced hepatocellular carcinoma (HCC) are not satisfactory because of the high rate of recurrence after treatment and because of severe complications after surgery. Cancer vaccines have been studied for decades to achieve effective, micro-invasive, long-lasting anti-tumor action. Cancer vaccines are designed to promote tumor-specific immune responses and increase specific cytotoxic CD8-positive T cells. This review summarizes 16 phase I clinical trials of cancer vaccines against HCC that have been conducted over the past 10 years. According to those trials, the Alpha fetoprotein (AFP), Glypican-3 (GPC3), and Multidrug resistance-associated protein 3 (MRP3) vaccines were well tolerated and safe. Some early clinical trials have shown that vaccination resulted in a large number of T cells activated by a specific tumor-associated antigen in the circulation, but clinical outcomes were not satisfactory. This may be because targets for immunosuppressive agents have yet to be clearly determined in HCC. Therapeutic regimens that combine activative agents and suppressive agents may profoundly improve clinical outcomes for patients with HCC in the future.
Cholangiocarcinoma (CC) accounts for about 3% of all gastrointestinal tumors and is the second most common primary liver tumor. Quality guidelines on CC are needed to guide hepatobiliary surgeons. Here, current guidelines on CC were reviewed to provide useful information and suggestions to help institutes and organizations all around the world to draft better guidelines on CC. Literature databases were electronically searched to identify guidelines or consensus statements regarding CC published from 2002-2016. Nine guidelines were included in this review. Comparison of the current guidelines revealed several inconsistencies. Signs of conflicting views indicated a lack of high level evidence. More studies need to be conducted in areas of contention to help update the guidelines. Organizations and medical societies need to be encouraged to use standard evaluation measures, to restrict tumors to CC or iCC, pCC, or dCC specifically, to give recommendations in accordance with the equipment that is available for diagnosis and treatment in different counties, and to use an appropriate and consistent structure when establishing and drafting guidelines for CC.
Subjective well-being (SWB) of older adults could be affected by both individual and community characteristics. However, the effect of community characteristics, such as population aging in local areas, remains unclear. This study examined the cross-sectional and longitudinal associations between the area-level population aging and SWB of older individuals from two distinct surveys. Those analyzed were 572 respondents aged 75 years and older for a cross-sectional survey in a metropolitan area in Tokyo, Japan (Study 1) and 1,257 and 859 respondents for a cross-sectional and longitudinal analysis, respectively, for a 2-year longitudinal survey project in urban and rural areas of Fukui Prefecture (Study 2). Area-level population aging was assessed by the number of people aged 65 years or older per 100 residents. SWB was assessed with the Life Satisfaction Index-A (LSIA). Multilevel analysis was performed to examine unconditional and conditional associations between the area-level number of older adults per 100 residents and the individual-level LSIA scores. The area-level number of older adults per 100 residents was significantly and positively associated with the LSIA scores in Study 1 (p = 0.042), even after controlling for the area- and individual-level covariates. In Study 2, we also found a significant effect of the area-level number of older adults per 100 residents on LSIA scores in the longitudinal multivariate analysis (p = 0.049). Findings from two survey projects suggested cross-validity in the positive effect of area-level population aging on older adults’ SWB. Policymakers should consider older citizens' SWB in the recent urban-to-rural migration governmental policy as well as in urban renovation planning.
Little is known about the acceptance and actual uptake of pre-exposure prophylaxis (PrEP) and associated factors in men who have sex with men (MSM) in China. This study is the baseline survey of an intervention study designed to evaluate the effectiveness of tenofovirdisoproxil fumarate (TDF) on a daily use for human immunodeficiency virus (HIV) prevention among MSM in Shanghai, China. From October 2012 to December 2013, a total of 1,033 MSM in Shanghai were recruited by local district Centers for Disease Control and Prevention (CDC) and a MSM community-based non-governmental organization (NGO). Among them, 197 (19.1%) participants expressed willingness to use the TDF group at baseline survey, but only 26 (2.5%) participated in the TDF group and took TDF one tablet a day. Higher willingness to use PrEP was associated with being 45 years or older, non-local residents, having more male sex partners in the past 6 months and not using condom at last anal sex with man. Acutal uptake of PrEP was associated with having ≥ 11 male sex partners in lifetime and reporting no female sex partners in lifetime. Reasons for not participating in TDF group among those who expressed willingness to use PrEP at baseline survey included loss of contact, ineligiblity because of abnormal results for liver or renal function tests, change of mind, and HIV seroconversion before uptake of PrEP. Our findings suggest that promotion of PrEP in MSM remains challenging at current circumstancein China. Future research is needed to solicit effective education and intervention programs to promote acceptance of PrEP among Chinese MSM.
Spontaneous esophageal perforation (Boerhaave's syndrome) is an uncommon and challenging condition with significant morbidity and mortality. Surgical treatment is indicated in the large majority of cases and different procedures have been described in this respect. We present the results of a mono-institutional evaluation of the management of spontaneous esophageal perforation over a 20-year period. The charts of 25 patients with spontaneous esophageal perforation treated at the Surgical Department of the University Hospital of Lausanne were retrospectively studied. In the 25 patients, 24 patients were surgically treated and one was managed with conservative treatment. Primary buttressed esophageal repair was performed in 23 cases. Nine postoperative complications were recorded, and the overall mortality was 32%. Despite prompt treatment postoperative morbidity and mortality are still relevant. Early diagnosis and definitive surgical management are the keys for successful outcome in the management of spontaneous esophageal perforation. Primary suture with buttressing should be considered as the procedure of choice. Conservative approach may be applied in very selected cases.
The aim of this study is to evaluate the pregnancy outcomes and prognoses for fetuses with ventriculomegaly. Two hundred and forty-one cases of fetuses with ventriculomegaly were included in this study. The subjects were divided into three groups according to their lateral ventricular width: "Mild Ventriculomegaly" (10 ‒ < 12 mm), "Moderate Ventriculomegaly" (12 ‒ < 15 mm) and "Severe Ventriculomegaly" (≥ 15 mm). Pediatric examination records and telephone interviews were conducted to track the outcomes of children until the age of 9 years. Eight-two cases were Isolated Ventriculomegaly (34.0%), while Non-Isolated Ventriculomegaly was found in 159 cases (66.0%). The pregnancy was terminated in 91 cases, and a higher abortion ratio was found in the NIVM (Non-Isolated Ventriculomegaly) group compared with the IVM (Isolated Ventriculomegaly) group. The fetuses were delivered in 150 cases, and four infants suffered deaths with NIVM. Of the surviving fetuses, 7 with IVM and 9 with NIVM showed significant abnormalities. The Mild and Moderate VM groups had more favorable prognoses compared with the Severe VM group. Regarding the outcomes and progression of lateral ventricular width, 1 out of 42 cases in the regressed group and 19 out of 108 cases in the stable group showed significant abnormalities. This study suggests that the degree and the progression of ventricular dilatation are main factors that affect pregnancy outcomes and prognoses.
Chemoresistance is a serious problem for the treatment of androgen-independent prostate cancer (PC). The underlying molecular mechanisms by which androgen-independent PC cells acquire the capacity to proliferate remain largely unclear. The aim of this study was to investigate the biological role of prostaglandin reductase 1 (PTGR1) in prostate cancer. Data from the Oncomine database showed that PTGR1 is commonly upregulated in PC tissue in comparison to corresponding normal controls. Two PTGR1-specific short hairpin RNA (shRNA) sequences were used to block the expression of PTGR1 via a lentivirus-mediated system in the androgen-independent PC cell lines DU145 and PC 3. Functional analysis revealed that knockdown of PTGR1 significantly inhibited proliferation and colony formation by PC cells. The inhibition of cell proliferation was related to arrest of the cell cycle in the G0/G1 phase and increased apoptosis in response to PTGR1 knockdown as indicated by flow cytometry. PTGR1 silencing was found to mechanically enhance the expression of p21, caspase 3, and cleaved PARP and to decrease the level of cyclin D1. In conclusion, PTGR1 plays an essential role in PC cells and may be a potential therapeutic target for PC.
Apolipoproteins are of great physiological importance and are associated with different diseases. Many independent studies of patterns of gene expression during osteoblast differentiation have been described, and some apolipoproteins have been induced during this process. 17-β-estradiol (E2) may enhance osteoblast physiological function. However, no studies have indicated whether E2 can modulate the expression of apolipoproteins during osteoblast differentiation in vitro. The aim of the current study was to observe the regulation of apolipoprotein mRNA expression by E2 during this process. Primary osteoblasts were collected from the calvaria of newborn mice and were subjected to osteoblast differentiation in vitro with serial concentrations of E2. RNA was isolated on days 0, 5, and 25 of differentiation. Real-time PCR was performed to analyze the levels of apolipoprotein mRNA. Results showed that during osteoblast differentiation all of the apolipoprotein genes were up-regulated by E2 in a dose-dependent manner. Moreover, only ApoE was strongly induced during the mineralization of cultured osteoblasts. This result suggests that ApoE might be involved in osteoblast differentiation. The hypothesis is that E2 promotes osteoblast differentiation by up-regulating ApoE gene expression, though further study is needed to confirm this hypothesis.
Unintentional injury in children is a worldwide public health problem, as it increases the health burden and is a leading cause of death among children. It is important to understand the differences between different age groups of children in regard to unintentional injury, in order to effectively implement child safety education. The present study aimed to determine the current trends of unintentional injury in children, and to identify the differences between different age groups of children with regard to unintentional injury. We identified 1,521 children who attended an 18-month health checkup (18-month group), and 1,368 children who attended a 36-month health checkup (36-month group), between January 1, 2014 and December 31, 2014. The rate of hospital visits associated with unintentional injury was 10.6% (161/1,521) in the 18-month group, and 13.1% (180/1,368) in the 36-month group. In both groups, present/past illness was associated with hospital visits, and in the 36-month group, hospital visits were more common in boys than in girls. The number of unintentional injuries that occurred outdoors was higher in the 36-month group than in the 18-month group. Unintentional injuries resulting from accidental ingestion and falls were more common in the 18-month group, while unintentional injuries resulting from turning over were more common in the 36-month group. In conclusion, the number of hospital visits for unintentional injury might be higher, and the number of preventive actions taken by mothers might be lower, among children attending the 36-month health checkup than among those attending the 18-month health checkup.
Yellow fever is a vector-borne disease endemic to tropical regions of Africa and South America. A recent outbreak in Angola caused hundreds of deaths. Six cases of yellow fever imported from Angola were reported recently in China. This raised the question of whether it will spread in China and how it can be prevented. This article discusses the possibility of yellow fever transmission in China and the strategies to counter it.