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Background With the recent certification by World Health Organization that the People’s Republic of China is malaria-free, it is timely to consider how elimination of malaria was completed in People’s Republic of China over the last 7 decades. Of the four widespread species of human malaria, Plasmodium vivax was the last to be eliminated by the national program of China. Understanding the incubation periods and relapses patterns of P. vivax through historical data from China is relevant for planning disease elimination in other malaria-endemic countries, with residual P. vivax malaria. Methods We collated data from both published and unpublished malaria parasite inoculation experiments conducted between 1979 and 1988 with parasites from different regions of the People’s Republic of China. The studies had at least two years of follow-up. We categorized P. vivax incubation patterns via cluster analysis and investigated relapse studies by adapting a published within-host relapse model for P. vivax temperate phenotypes. Each model was fitted using the expectation-maximization (EM) algorithm initialized by hierarchical model-based agglomerative clustering. Results P. vivax parasites from the seven studies of five southern and central provinces in the People’s Republic of China covering geographies ranging from the south temperate to north tropical zones. The parasites belonged to two distinct phenotypes: short- (10–19 days) or long-incubation (228–371 days). The larger the sporozoite inoculation, the more likely short incubation periods were observed, and with more subsequent relapses (Spearman’s rank correlation between the number of inoculated sporozoites and the number of relapses of 0.51, p-value = 0.0043). The median of the posterior distribution for the duration of the first relapse interval after primary infection was 168.5 days (2.5% quantile: 89.7; 97.5% quantile: 227.69 days). The predicted survival proportions from the within-host model fit well to the original relapse data. The within-host model also captures the hypnozoite activation rates and relapse frequencies, which consequently influences the transmission possibility of P. vivax. Conclusions Through a within-host model, we demonstrate the importance of clearance of hypnozoites. A strategy of two rounds of radical hypnozoite clearance via mass drug administration (MDA) deployed during transmission (summer and autumn) and non-transmission (late spring) seasons had a pronounced effect on outbreaks during the malaria epidemics in China. This understanding can inform malaria control strategies in other endemic countries with similar settings.

Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide, produced by aquatic cyanobacteria such as microcystis, with strong reproductive toxicity which poses greater threat to the reproductive abilities of humans and animals. By exploring the role of trimethylation of histone H3 at lysine 4 (H3K4me3) and the role of oxidative stress in MC-LR-induced apoptosis in testicular Sertoli cells in Sprague-Dawley (SD) rats, this study indicated that MC-LR increased the expression levels of apoptosis-related genes by raising the levels of H3K4me3. 5'-Deoxy-5'-methylthioadenosine (MTA), the inhibitor of H3K4me3, reduced apoptosis, indicating for the first time that epigenetic modification is closely related to the testicular reproductive toxicity induced by MC-LR. MC-LR also induced oxidative stress by stimulating the generation of reactive oxygen species (ROS), and subsequently triggering mitochondria-mediated apoptotic pathway by decreasing mitochondrial membrane potential and increasing the levels of Bax, Bcl-2, Caspase-3, and so on. MC-LR-induced apoptosis of testicular cells could be decreased after pretreatment with oxidative stress inhibitor N-acetyl-cysteine (NAC). Furthermore, the pathological damage to mitochondria and testes were observed in SD rats. These results show that MC-LR can induce apoptosis by raising the levels of H3K4me3, and pretreatment with MTA can ameliorate the MC-LR-induced apoptosis of cocultured cells by lowering the levels of H3K4me3. Furthermore, NAC has a protective effect on MC-LR-induced apoptosis of testicular cells in SD rats by inhibiting the oxidative stress.

The liver is an important iron storage site and a primary MC-LR target. C57BL/6 and Hfe−/− mice were used to investigate effects and mechanisms of MC-LR on systematic iron homeostasis. Body weight, tissue iron content, hematological and serological indexes, and histopathological were evaluated. Ultrastructure and iron metabolism-related genes and proteins were analyzed. MC-LR induced dose-dependent increases in red blood cells, hemoglobin, and hematocrit. In contrast MC-LR-induced dose-dependent decreases in mean corpuscular volume, hemoglobin, and hemoglobin concentration were observed both C57BL/6 and Hfe−/− mice. In both mouse species, serological indexes increased. Aggravated liver and spleen iron were observed in C57BL/6 mice, consistent with Perls’ Prussian blue staining. However, an opposite trend was observed in Hfe−/− mice. C57BL/6 mice had lower Hamp1 (Hepcidn), Bmp6, Il-6, and Tmprss6. Significant increased Hjv, Hif-1α and Hif-2α were observed in both C57BL/6 and Hfe−/− mice. MC-LR-induced pathological lesions were dose-dependent increase in C57BL/6 mice. More severe pathological injuries in MC-LR groups (25 μg/kg) were observed in Hfe−/− mice than in C57BL/6 mice. In Hfe−/− mice, upon exposure to 25 μg/kg MC-LR, mitochondrial membranes were damaged and mitochondrial counts increased with significant swelling. These results indicated that MC-LR can induce the accumulation of iron in C57BL/6 mice with the occurrence of anemia, similar to thalassemia. Moreover, dysregulation of iron homeostasis may be due to MC-LR-induced Hamp1 downregulation, possibly mediated by hypoxia or the IL6–STAT3 and BMP–SMAD signaling pathways.

A smart polycarbonate(PCA) copolymer-based nanoparticle(NanoPCA) with pH-responsive, long-term stability, and tumor targeting ability was successfully developed by synthesizing and assembling a series of functional PCA-based copolymers including poly(2-amino-1,3-propanediol carbonate-co-L-lactide)[P(CA-co-LA)], poly(2-amino-1,3-propanediol carbonate-co-L-lactide)-g-methoxy-poly(ethylene glycol)[P(CA-co-LA)-g-MPEG], and poly(2-amino-1,3-propanediol carbonate-co-L-lactide)-g-poly(ethylene glycol)-cyclic(Arg-Gly-Asp-D-Phe-Lys) [P(CA-co-LA)-g-PEG-cRGD] for targeted anticancer drug delivery. pH-Responsive studies demonstrated that the loading doxorubicin(DOX) released faster from NanoPCA at acidic conditions due to protonation effects of P(CA-co-LA) copolymers. Furthermore, the in vitro and in vivo investigations demonstrate that the DOX-loaded NanoPCA exhibited significant tumor targeting ability, outstanding antitumor effect and excellent biological safety in the treatment of oral squamous cell carcinoma(OSCC). Therefore, this work provides a promising drug delivery platform for cancer therapy and other applications.

Ectopic thoracic kidneys are the rarest form of renal ectopia. Moreover, congenital abnormality of a primary anterior inferior vena cava (IVC) located behind the anterior abdominal wall is extremely rare. To date, only one such case has been reported. Herein, we report a rare case of a 55-year-old Chinese male with bilateral thoracic kidneys combined with an anterior IVC, a malformed liver, and a large-round-folds navel. The classification, clinical characteristics, and management options of a thoracic kidney was also summarized by literature review. To our best knowledge, the simultaneous detection of such multiple complex abnormalities has not been reported.

Background: To investigate the epidemiologic features of breast cancer laterality and molecular subtypes in Southern China, we retrospectively analyzed the clinical data of patients with a definite diagnosis of breast cancer in 2013-2017. Methods: Data for inpatient hospitalization associated with breast cancer were obtained from the Affiliated Hospital of Guangdong Medical University, Guangdong Province, South China. Around 2060 cases who were diagnosed with unilateral breast cancer for the past 5 years were classified based on laterality and molecular subtypes. Molecular subtypes were defined in accordance with the 2013 St. Gallen recommendations. All statistical analyses were performed using Statistical Product and Service Solutions version 21 and Excel version 2010. Results: Breast cancer is more likely to be diagnosed in the left breast than in the right by around 5%. In both in situ and invasive carcinomas, the right breast is more commonly affected than the left in young (

Introduction Dynamin 3 (DNM3) is a large GTPase that possesses mechanochemical properties and has been shown to be involved in malignancies. However, most studies about DNM3 are observational, and knowledge of the precise molecular mechanism of DNM3 remains limited. Materials and methods We constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, which was then transfected into SW620 and LoVo cells. One cell line was divided into three groups. DNM3 mRNA and protein expression was analyzed by quantitative real-time PCR and Western blot assay. To investigate DNM3 biological activity in colon cancer SW620 and LoVo cell line, we performed cell proliferation, transwell migration, and invasion assay. Matrix metalloproteinase (MMP)-2 and MMP-9 protein expressions were detected by Western blot. Result We successfully constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, and stable DNM3 expression was observed in SW620 and LoVo cell lines. The vector overexpressing DNM3 inhibited the proliferation, weak invasion, and migration ability of colon cancer SW620 and LoVo cells relative to those in the control group (all P

Microcystins (MCs) are produced by certain bloom-forming cyanobacteria that can induce toxicity in various organs, including renal toxicity, reproductive toxicity, cardiotoxicity, and immunosuppressive effects. It has been a significant global environmental issue due to its harm to the aquatic environment and human health. Numerous investigators have demonstrated that MC exposure can induce a widespread epidemic of enterogastritis with symptoms similar to food poisoning in areas close to lakes. Both in vivo and in vitro studies have provided evidence of positive associations between MC exposure and gastrointestinal toxicity. The toxicity of MCs on the gastrointestinal tract is multidimensional. MCs can affect gastrointestinal barrier function and shift the structure of gut microbiota in different gut regions. Furthermore, MCs can inhibit the secretion of gastrointestinal digestive enzymes and the release of inflammatory cytokines, which affects the expression of immune-related genes in the intestine. The damage of the intestine is closely correlated to MC exposure because the intestine is the main site for the digestion and absorption of nutrients. The damage to the gastrointestinal tract due to MCs was summarized from different aspects, which can be used as a foundation for further exploration of molecular damage mechanisms.

AIM: To evaluate the associations between development of retinopathy of prematurity (ROP) and serum lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). METHODS: A retrospective cohort study was performed, involving infants who were screened for ROP from January 2015 to December 2015. Preterm newborns of ≤32 gestational weeks with ROP were enrolled as the observation group, and non-ROP infants were enrolled as the control group, whose complete blood cell were measured within the first 24h of life. The levels of NLR, LMR and PLR were determined in all groups. The data obtained were analyzed using univariate and multivariate logistic regression analysis. RESULTS: In this study, 40 cases of ROP were enrolled and 40 cases of non-ROP as controls. The LMR levels were significantly higher (P

Background Malaria was once a serious public health problem in China, with Plasmodium vivax the major species responsible for more than 90% of local transmission. Following significant integrated malaria control and elimination programmes, malaria burden declined, and since 2017 China has not recorded any indigenous case. To understand the historical malaria transmission patterns and epidemic characteristics in China and insights useful to guide P. vivax malaria control and elimination elsewhere, a retrospective study was carried out. Methods Historical data from a pilot study conducted in Guantang, Luyi in central China from 1971–1995, were digitized. The data included monthly numbers of reported cases, febrile cases, parasite carriage rates, the neonatal infection rate, and entomological data regarding Anopheles sinensis. Results Following 25 years of continuous integrated malaria control activities, malaria incidence in Guantang decreased from 4,333 cases per 10,000 in 1970 before integrated implementation to 0.23 cases per 10,000 in 1991, and no cases in 1992–1995. Some fluctuations in incidence were observed between 1977 and 1981. During the period parasite rates, antibody levels and the neonatal infection rate also decreased. The pattern of seasonality confirmed that P. vivax in Henan Province was primarily of the long incubation type (temperate) during non-transmission period. The findings retrospectively provide a scientific basis for the implementation of mass campaigns of liver stage hypnozoite clearance. Entomological studies indicated that An. sinensis was the only vector, and it preferred bovine to human hosts, predominantly biting and resting outdoors. Mosquito densities declined between 1971 and 1984. Conclusion The integrated malaria control approach in Guantang effectively controlled malaria and achieved elimination. Analysis of the effectiveness of the programme can provide guidance to other regions or countries with similar ecological settings aiming to move from malaria control to elimination. There is a potential challenge in the maintenance of non-transmission status owing to imported cases and the long dormancy of liver stage hypnozoites.

Surface-layer proteins are located in a paracrystalline layer outside the bacterial cell wall and are thought to play a role in the adherence. However, the functions of S-layer proteins are not yet completely revealed and it has been proposed that these structures protect the microbe from hostile environmental agents and aid in maintaining cellular integrity. In this study, the Lactobacillus paracasei M7 strains showed to inhibit the adhesion of Salmonella to epithelial cells, a process which may be related to specific component of the bacterial surface. Human epithelial HT-29 cells were treated with S-layer proteins after Salmonella infection, or were pretreated with S-layer proteins prior to infection to determine their importance in the inhibition of pathogen adherence.

Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide hepatotoxin produced by cyanobacteria. MicroRNA-122 (miR-122) is specifically expressed in the liver. This study focuses on the role of miR-122 in MC-LR-induced dysregulation of hepatic iron homeostasis in C57BL/6 mice. The thirty mice were randomly divided into five groups (Control, 12.5 μg/kg·BW MC-LR, 25 μg/kg·BW MC-LR, Negative control agomir and 25 μg/kg·BW MC-LR + miR-122 agomir). The results show that MC-LR decreases the expressions of miR-122, Hamp, and its related regulators, while increasing the content of hepatic iron and the expressions of FPN1 and Tmprss6. Furthermore, miR-122 agomir pretreatment improves MC-LR induced dysregulation of hepatic iron homeostasis by arousing the related regulators and reducing the expression of Tmprss6. These results suggest that miR-122 agomir can prevent the accumulation of hepatic iron induced by MC-LR, which may be related to the regulation of hepcidin by BMP/SMAD and IL-6/STAT signaling pathways.

MgAlCr-CrO42−-LDHs materials were prepared via a hydrothermal method by doping Cr3+ in hydroxide laminates and inserting colored CrO42− to replace the interlayer anions of LDHs materials. This method can optimize the performance of photocatalysis. The samples were characterized by X-ray diffraction, high-resolution transmission electron microscopy, Fourier infrared spectrometry, X-ray photoelectron spectroscopy, and UV–VIS–NIR spectrophotometry. Density functional theory was used to calculate the electron density of states. The effects of Cr3+ and CrO42− on the structure, morphology, electronic structure, VIS-NIR spectrum, and photocatalytic properties were systematically studied, especially the synergistic enhancement effect on the spectrum and catalysis property of MgAl-LDHs materials. The results indicated that the impurities of Cr3+ introduced double characteristic absorption peaks at 400 nm and 570 nm, which improved the absorption of the visible light spectrum of MgAl-LDHs. The CrO42− anion reduced the band gap width, thus enhancing the absorption of low-energy photons. Under the synergistic influence of these effects, the VIS absorptance of MgAl-LDHs was enhanced by 57%, and the color changed from white to dark brown, which proved that the absorption of solar radiation was significantly enhanced. Finally, the interaction between cations and anions enhanced the photocatalytic performance, leading to an apparent photodegradation rate (Kapp) and half-life (t1/2) of methylene blue that reached 0.0174 min−1 and 40 min, respectively. This study is expected to provide a new approach for designing high-performance hydrotalcite photocatalytic materials.

As an emerging pollutant in the aquatic environment, microcystin-LR (MC-LR) can enter the body through multiple pathways, and then induce apoptosis and gonadal damage, affecting reproductive function. Previous studies focused on male reproductive toxicity induced by MC-LR neglecting its effects on females. The apoptotic signal-regulated kinase 1 (ASK1) is an upstream protein of P38/JNK pathway, closely associated with apoptosis and organ damage. However, the role of ASK1 in MC-LR-induced reproductive toxicity is unclear. Therefore, this study investigated the role of ASK1 in mouse ovarian injury and apoptosis induced by MC-LR. After MC-LR exposure, ASK1 expression in mouse ovarian granulosa cells was increased at the protein and mRNA levels, and decreased following pretreatment by antioxidant N-acetylcysteine, suggesting that MC-LR-induced oxidative stress has a regulatory role in ASK1 expression. Inhibition of ASK1 expression with siASK1 and NQDI-1 could effectively alleviate MC-LR-induced mitochondrial membrane potential damage and apoptosis in ovarian granulosa cells, as well as pathological damage, apoptosis and the decreased gonadal index in ovaries of C57BL/6 mice. Moreover, the P38/JNK pathway and downstream apoptosis-related proteins (P-P38, P-JNK, P-P53, Fas) and genes (MKK4, MKK3, Ddit3, Mef2c) were activated in vivo and vitro, but their activation was restrained after ASK1 inhibition. Data presented herein suggest that the ASK1-mediated P38/JNK pathway is involved in ovarian injury and apoptosis induced by MC-LR in mice. It is confirmed that ASK1 has an important role in MC-LR-induced ovarian injury, which provides new insights for preventing MCs-induced reproductive toxicity in females.

// Liang Jiang 1 , Gao-Le Yuan 1 , Qi-Lian Liang 1 , Hui-Jie Zhang 1 , Jie Huang 1 , Shao-Ang Cheng 1 and Xiao-Xia Peng 1 1 Oncology Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China Correspondence to: Qi-Lian Liang, email: // Keywords : YB-1, NSCLC, IHC, prognosis, meta-analysis Received : October 08, 2016 Accepted : January 10, 2017 Published : January 18, 2017 Abstract Background: Y-box binding protein 1 (YB-1) belongs to the cold shock domain protein family involved in transcription and translation. We conducted a meta-analysis of the association between YB-1 expression and the survival and clinicopathological features in NSCLC. Methods: PubMed and Embase were searched to identify studies that evaluated the YB-1 expression (by immunohistochemistry) and overall survival (OS) in NSCLC. Hazard ratios (HRs) and 95% confidence intervals (CI) of OS were pooled. Odds ratios (ORs) of clinicopathological features were computed. Meta-analysis was performed using STATA 12.0 software. Results: Data on 692 NSCLC patients were collected from six eligible studies. Meta-analysis revealed that YB-1 was associated with worse OS (HR = 1.59, 95% CI [1.27, 2.00], P < 0.001, fixed effect), tumor stage (OR = 0.43, 95% CI [0.22-0.82], P = 0.01, random effect), and depth of invasion (OR = 0.37, 95%CI [0.22-0.63], P < 0.001, fixed effect). A subgroup was analyzed by IHC staining to determine the location of YB-1 positive expression. Poor OS was observed in nucleus staining (pooled HR = 1.86, 95% CI [1.41, 2.45], P < 0.001). However, no statistical significance was observed in combined cytoplasmic and nuclear staining (pooled HR = 1.14, 95% CI [0.76, 1.72], P = 0.536). Conclusions: Meta-analysis indicated that YB-1 overexpression is correlated with worse OS and clinicopathological features in NSCLC. Subgroup analysis revealed that the nucleus expression of YB-1 may be more closely associated with NSCLC prognosis than cytoplasmic expression.

Organic anions have been intercalated into the interlayer of Mg-Al layered double hydroxides (LDHs) via a hydrothermal method to tune the visible and near-infrared reflection spectrum of hybrid pigments based on LDHs. The prepared samples were analyzed by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, thermogravimetric-differential scanning calorimetry, visible and near-infrared spectrophotometry, and CIE 1976 L*a*b* color scales. The effects of the intercalated organic anions on the structure, morphology, color, and spectral characteristics of Mg-Al LDH materials were systematically investigated. The results show that the colored anions of acid green (AG) and acid yellow (AY) have been successfully intercalated into the interlayer space of LDHs through the anion displacement process. The visible light reflection spectrum of LDH matrix can be easily tuned by adjusting the intercalated concentration of anions and the relative ratio of AG and AY, which leads to the color of prepared samples changing from the original white into blue, yellow, green, and dark black. Combined with the color adjusting ability of organic anions and the high hydroxyl property of LDH substrate, the typical visible and near-infrared spectral characteristics of natural green plants can be accurately simulated. The correlation coefficient of spectrum shape between the prepared pigment and green plant in the whole range of 400–2500 nm is as high as 0.94. Moreover, the thermal stability of LDH materials is improved by the intercalated organic anions, whose spectral properties can withstand high temperatures of at least 250 °C. The hybrid materials could be used as a functional pigment to prepare green camouflage coatings, showing their potential application in the field of hyperspectral camouflage.

A proliferation of chemical, reaction and enzyme databases, new computational methods and software tools for data-driven rational biosynthesis design have emerged in recent years. With the coming of the era of big data, particularly in the bio-medical field, data-driven rational biosynthesis design could potentially be useful to construct target-oriented chassis organisms. Engineering the complicated metabolic systems of chassis organisms to biosynthesize target molecules from inexpensive biomass is the main goal of cell factory design. The process of data-driven cell factory design could be divided into several parts: (1) target molecule selection; (2) metabolic reaction and pathway design; (3) prediction of novel enzymes based on protein domain and structure transformation of biosynthetic reactions; (4) construction of large-scale DNA for metabolic pathways; and (5) DNA assembly methods and visualization tools. The construction of a one-stop cell factory system could achieve automated design from the molecule level to the chassis level. In this article, we outline data-driven rational biosynthesis design steps and provide an overview of related tools in individual steps.

Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide intracellular toxin released by cyanobacteria that exhibits strong reproductive toxicity. However, little is known about its biotoxicity to the female reproductive system. The present study investigates unexplored molecular pathways by which oxidative stress acts on MC-LR-induced endoplasmic reticulum stress (ERs) and autophagy. In the present study, immortalized murine ovarian granular cells (KK-1 cells) were exposed to 8.5, 17, and 34 μg/mL (IC50) of MC-LR with or without N-acetyl-l-cysteine (NAC, 10 mM) for 24 h, and C57BL/6 mice were treated with 12.5, 25.0, and 40.0 μg/kg⋅bw of MC-LR with or without NAC (200 mg/kg⋅bw) for 14 days. The results revealed that MC-LR could induce cells apoptosis and morphologic changes in ovarian tissues, induce oxidative stress by stimulating the generation of reactive oxygen species (ROS), destroying antioxidant capacity, and subsequently trigger ERs and autophagy by inducing the hyper-expression of ATG12, ATG5, ATG16, EIF2α (phosphorylated at S51), CHOP, XBP1, GRP78, Beclin1, and PERK (Thr980). Furthermore, NAC pretreatment partly inhibited MC-LR-induced ERs and autophagy via the PERK/ATG12 and XBP1/Beclin1 pathways. These results suggest that oxidative stress mediated MC-LR-induced ERs and autophagy in KK-1 cells and C57BL/6 mice ovaries. Therefore, oxidative stress plays an important role in female toxicity induced by MC-LR.

The chest and abdomen soft tissue injury risk to three-year old (3YO) child occupant in a child restraint system (CRS) was investigated by using finite element (FE) simulation, based on the UN R129 dynamic test regulation. In which, Q3 dummy FE models and THUMS 3YO Occupant Model Academic Version 4 (THUMS 3YO) and two types of CRSs (impact shield and five-point harness) were used. The chest physical injury parameters, and the chest soft inner organs parameters were compared in two types of CRSs. The simulation result shows that significant difference of chest deformation observed in Q3 and THUMS 3YO. The stress and strain distribution of chest and abdomen visceral organs of THUMS 3YO in the two CRSs were larger than the injury threshold. Moreover, in the impact shield CRS, the distribution of the stress-strain and absolute value was larger, to predict a higher chest injury risk.

Radiotherapy is a vital treatment option for patients with nasopharyngeal carcinoma (NPC). Concurrent cisplatin-based radiochemotherapy with or without adjuvant chemotherapy had acquired good clinical effects with good local control rates. However, a number of patients present with metastasis following systemic regimens or initial diagnosis of locally advanced NPC, which cause difficulty for subsequent therapy. Therefore, there is an urgent requirement to discover novel targeted therapies. The present report describes one case of a patient with NPC and multiple metastases. The patient was treated with systemic therapy in combination with bevacizumab, palliative radiotherapy and chemotherapy following treatment with cetuximab and concurrent chemoradiotherapy in 2015. Following the addition of bevacizumab, metastases were reduced or disappeared after >2 months, and the duration of progression-free survival was 7 months. Bevacizumab is a monoclonal antibody that targets VEGF, and it is associated with angiogenesis, which causes the growth, invasion and progression of tumors. In previous studies, bevacizumab has been approved for the treatment of several types of malignant cancer and it has been able to effectively improve prognosis. In the present review, the effect of adding bevacizumab to systemic therapy for the treatment of NPC was analyzed, with a particular focus on advanced and metastatic diseases. A growing number of phase I/II clinical trials involving bevacizumab for NPC have been conducted with clinical outcomes showing improved rates of overall survival and progression-free survival as well as improvements in the quality of life of patients. However, severe or deadly toxicities can also result from combination treatment with bevacizumab. In the future, bevacizumab may become a common addition to systemic therapy for the treatment of locally advanced and metastatic NPC.

Microcystin-leucine arginine (MC-LR) is a variant of microcystins (MCs), which poses a serious threat to the reproductive system. Histone acetylation modification can regulate the expressions of apoptosis-related genes. However the mechanisms of histone acetylation involving MC-LR-induced apoptosis were not understood. This study investigated the change of histone acetylation and its role in apoptosis and cell cycle arrest induced by MC-LR. MC-LR enhanced the activity of histone deacetylase (HDAC), decreased the activity of histone acetylase (HAT), up-regulated the expression of HDAC1, and down-regulated the expressions of Ac-H3 and Ac-H4 in vitro and vivo. Meanwhile, MC-LR induced testicular tissue injury and increased the expressions of apoptosis-related genes, such as Bax, Caspase3 and Caspase8, ultimately causing cells apoptosis in testicular tissues. Furthermore, MC-LR also induced cell cycle arrest in S phase, increased the expression of P21Wif1/Cip1, and inhibited the expressions of cyclinD1, cyclinE1, CDK2 and E2F1. Importantly, HDAC inhibitor Trichostatin A (TSA) could ameliorate MC-LR-induced apoptosis and cell cycle arrest by reverse-regulating the expressions of these proteins. These results indicated that MC-LR could activate the mitochondrial apoptotic pathway and disorder the cell cycle pathway to induce the cell apoptosis by enhancing HDAC activity and reducing histone acetylation of normal testicular cells in SD rats. Hence, histone acetylation has a vital function in MC-LR-induced apoptosis in SD rat testicular cells, which provides a new insight on the reproductive toxicity of male induced by MC-LR.

Liver tissue interstitial fluid (TIF) a special microenvironment around liver cells, which may play a vital role in cell communication during liver injury. Moreover, toll-like receptor 4 (TLR4) is an important trigger of the immune response that may also play a role in liver injuries, including radiation-induced liver disease (RILD). Therefore, the purpose of this study was to identify the roles of the TLR4-dependent immune response and TIFs in RILD after radiation therapy (RT) for liver cancer. This study consisted of two phases, and in the primary phase, the livers of TLR4 mutant (TLR4(-)) and normal (TLR4(+)) mice were irradiated with 30 Gy. TIF was then obtained from mouse livers and assessed by cytokine array analysis 20 days after irradiation, and cytokines in the TIFs, TLR4 and RILD were analyzed. In the second or validation phase, hepatocytes were isolated from TLR4(+) or TLR4(-) mice irradiated with 8 Gy and were co-cultured with TIFs from mouse livers, apoptosis of the hepatocytes was then measured using flow cytometry. We found that severe RILD was accompanied by higher expression of granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor receptor 2(VEGFR-2) in liver TIFs, from in TLR4(+) mice compared with TLR4(-) mice (P0.05). In both TLR4(+) and TLR4(-) hepatocytes, apoptosis after irradiaton was increased significantly after co-culture in TIFs from TLR4(+) mice that had their livers irradiated, compared with TIFs from TLR4(-) mice that had their livers irradiated or TIFs from unirradiated mice (P0.05). In summary, these findings indicate that the TLR4-dependent immune response may promote RILD by enhancing the expression of GM-CSF, VEGFR-2 and TRAIL in liver TIFs.

Bisphenol A (BPA) is an industrial component commonly used in synthesis of polycarbonate plastics, epoxy resin and other polymer materials. Due to its mass productions and widespread applications, the presence of BPA is ubiquitous in the environment. BPA can enter the body via different ways such as digestive tract, respiratory tract and dermal tract. As an endocrine disruptor, BPA has estrogen-like and anti-androgen effects causing damages to different tissues and organs, including reproductive system, immune system and neuroendocrine system, etc. Recently, it has been shown that BPA could induce carcinogenesis and mutagenesis in animal models. Here, the underlying mechanisms of BPA-induced multi-organ toxicity were well summarized, involving the receptor pathways, disruption of neuroendocrine system, inhibition of enzymes, modulation of immune and inflammatory responses, as well as genotoxic and epigenetic mechanisms. The aim of this review is to compile the available current research data regarding BPA and provide an overview of the current status of BPA exposure and relevant health effects covering reproductive, developmental, metabolic, immuno, respiratory, hepatic and renal toxicity and carcinogenesis of BPA. This review provides comprehensive data of BPA toxicity on human health and related mechanisms. We also identify any missing data which should be addressed by further studies.

Background: The objective of this study was to explore the influence factors of hospitalization costs of treating colorectal cancer in China. And the study provides new estimates on hospitalization costs and length of hospital stay for patients with colorectal cancer in China. Methods: Data for inpatient hospitalization associated with colorectal cancer were obtained from a 3-tier hospital in Guangdong Province and were analyzed post hoc. We conducted descriptive statistical methods, Wilcoxon rank–sum tests (for 2 groups) and the Kruskal–Wallis test (for more than 2 groups) to analyze the hospitalization costs of treating colorectal cancer. Results: The analysis included 8021 patients (female: 40.54%; mean age; 61.80 ± 13.28 years; male: 59.46%; mean age: 61.80 ± 13.28 years). The overall mean length of hospital stay was 11.35 days. Over the 5 years, the mean length of hospital stay showed a small decrease from 12.22 days in 2012 to 10.69 days in 2016, while per-day costs showed a trend of increase between 2012 and 2015 (increase from

Toll-like receptor 4 (TLR4) is an important trigger of the immune response against hepatitis B virus (HBV) infection and liver injuries. The roles of HBV reactivation versus TLR4-dependant immune response may be critical factors in preventing radiation-induced liver diseases (RILDs) after liver cancer radiotherapy. This study consists of three phases. In the primary phase, livers of mutant TLR4 (TLR4(-)) mice were irradiated with 30 Gy in either the absence or presence of HBV infection. The latter was done by introduction of plasmid pAAV/HBV 1.2. In the advanced phase, RILDs were compared in normal TLR4 (TLR4(+)) versus TLR4(-) mice. In the validation phase, 28 liver cancer patients who had undergone radiotherapy before hepatectomy were enrolled. Liver biopsies near tumors, irradiated with 35-48 Gy, were used to construct tissue microarrays. HBV reactivation, TLR4 expression, and severity of RILDs were studied in both mouse and human. More HBV reactivation, without significant RILD, was observed in irradiated versus unirradiated TLR4(-) mice. RILD scores of TLR4(+) mice were higher than TLR4(-) mice. In humans, serious RILDs tended to develop in patients with high TLR4 expression, but not in patients with low TLR4 or high HBV surface antigen expression. High TLR4 expression was seen in only 2 of 12 HBV-reactive patients, but in HBV-nonreactive patients, it was seen in 6 of 9 (P < 0.03). In summary, RILDs correlated with high TLR4 expression, but not with HBV reactivation, which is inhibited in liver with high TLR4 expression after liver cancer radiotherapy.

The biology underlying bone-specific metastasis (BM) of hepatocellular carcinoma (HCC) is poorly understood. The goal of the present study is to further elucidate the molecular and cellular mechanisms underlying HCC with BM. The expression of connective tissue growth factor (CTGF) and interleukin-11 (IL-11) in RNA extracted from 127 formalin-fixed, paraffin-embedded HCC specimens was examined by quantitative real-time polymerase chain reaction. A cellular hypoxic model was established in vitro to investigate CTGF and osteoprotegerin (OPG) expression and roles in hypoxia-induced tumor aggressiveness. The mean CTGF expression in BM versus non-metastatic samples was 3.63-times higher, and IL-11 expression was detected in 62.5 % (10/16) of BM samples versus only in 18.9 % (21/111) of the non-metastatic ones. Highly metastatic HCC cell lines tended to show strong expression of CTGF and IL-11, but low expression of OPG. Hypoxic stimulation of HCC 97L cells increased the level of CTGF mRNA by 2.80-fold within 1.5 h, and hypoxia-inducible factor-1α mRNA levels in these cells could be increased by stimulation with recombinant CTGF protein. Furthermore, OPG and matrix metalloproteinase-2 and -9 levels were also induced under hypoxic conditions. Expression levels of intratumoral CTGF or IL-11 were independent prognostic factors for the development of BM in HCC patients. Tumor hypoxia enhanced the expression of CTGF, which initiates the invasive angiogenesis cascade and enhances expression of many hypoxia-associated genes. Cellular release of OPG may play a role in tumor cell survival. The hypoxia-induced cascade in HCC cells may contribute to invasion and metastasis in vivo.

Purpose To determine whether factors secreted by irradiated liver nonparenchymal cells (NPCs) may influence invasiveness and/or metastatic potential of hepatocellular carcinoma (HCC) cells and to elucidate a possible mechanism for such effect. Methods and Materials Primary rat NPCs were cultured and divided into irradiated (10-Gy X-ray) and nonirradiated groups. Forty-eight hours after irradiation, conditioned medium from irradiated (SR) or nonirradiated (SnonR) cultures were collected and added to sublethally irradiated cultures of the hepatoma McA-RH7777 cell line. Then, hepatoma cells were continuously passaged for eight generations (RH10Gy-SR and RH10Gy-SnonR). The invasiveness and metastatic potential of McA-RH7777, RH10Gy-SnonR, and RH10Gy-SR cells were evaluated using an in vitro gelatinous protein (Matrigel) invasion and an in vivo metastasis assay. In addition, SR and SnonR were tested using rat cytokine antibody arrays and enzyme-linked immunosorbent assay (ELISA). Results In vitro gelatinous protein invasion assay indicated that the numbers of invading cells was significantly higher in RH10Gy-SR (40 ± 4.74) than in RH10Gy-SnonR (30.6 ± 3.85) cells, and lowest in McA-RH7777 (11.4 ± 3.56) cells. The same pattern was observed in vivo in a lung metastasis assay, as evaluated by number of metastatic lung nodules seen with RH10Gy-SR (28.83 ± 5.38), RH10Gy-SnonR (22.17 ± 4.26), and McA-RH7777 (8.3 ± 3.8) cells. Rat cytokine antibody arrays and ELISA demonstrated that metastasis-promoting cytokines (tumor necrosis factor-α and interleukin-6), circulating growth factors (vascular endothelial growth factor and epidermal growth factor), and metalloproteinases (MMP-2 and MMP-9) were upregulated in SR compared with SnonR. Conclusions Radiation can increase invasiveness and metastatic potential of sublethally irradiated hepatoma cells, and soluble mediators released from irradiated NPCs promote this potential. Increased secretion of metastasis-related cytokines and factors from NPCs after irradiation may be a possible mechanism for the radiation-induced invasiveness and metastatic potential of HCC.

The aim of this study was to determine whether caffeine enhanced radiosensitivity of normal liver tissue in a rat radiation-induced liver disease model. Buffalo rat McA-RH7777 hepatocellular cancer cells and BRL3A normal liver cells were irradiated, and cell cycle distribution and apoptosis rates were analyzed. A rat model of radiation-induced liver disease was established, rats were randomized into four groups: control; caffeine alone; irradiation (IR) alone; and caffeine plus IR (Caff + IR) group. Apoptosis rates in normal rat liver tissue after IR were evaluated by TUNEL staining and caspase-3 Western blot. Transaminase activity was measured and histopathological examination was done after IR. Caffeine abrogated IR-induced G2 phase arrest (Caff + IR vs. IR: 40.9 ± 4.0 vs. 60.7 ± 5.5%, at 12 h after IR) and increased apoptosis rates (Caff + IR vs. IR: 56.1 ± 6.8 vs. 35.5 ± 4.0%, at 72 h after IR) in McA-RH7777 cells, but did not affect IR-induced G2 phase arrest and apoptosis rates at any time point after IR in BRL3A cells. Caffeine did not enhance apoptosis, transaminase activity, or histopathological injury of normal rat liver tissue at any time points after IR. This study suggests that caffeine might not enhance radiosensitivity of normal liver tissue in vivo. In an earlier study, we reported that caffeine enhanced radiosensitivity of human hepatocellular cancer in a nude mice model. Together, these results offer feasibility of clinical application.

We analyzed malaria prevalence and evaluated the effect of malaria control measures in Henan Province, People's Republic of China between 1993 and 2004. Data relating to malaria epidemics, malaria control measures and their effects, and vector surveillance between 1993 and 2004 were collected and analyzed. Mean malaria incidence during this period was 2.96/100,000. After integrated vector control measures and appropriate treatment of malaria cases were carried out, the number of malaria cases in Henan Province decreased from 4,815 in 2000 to 2,112 in 2004. The parasite-positive rate and the density of Anopheles anthropophagus were also reduced. Malaria control measures were effective and malaria incidence decreased in Henan. However, there are still more cases in this province than in 1992. Local malaria outbreaks and epidemics have occurred in areas where Anopheles anthropophagus and An. sinensis are present. Thus, malaria control measures should be strengthened.

Background The optimal treatment for adrenal metastases from hepatocellular carcinoma (HCC) has not been established. This study analyzed the effects of radiation therapy (RT) for such metastases and identified clinical features and predictors of survival in these patients. Methods We retrospectively investigated 55 patients with adrenal metastasis from HCC who had been treated with RT. Radiation doses to the adrenal lesions ranged from 26 to 60 Gy, while the intrahepatic lesions were treated by surgical resection, transarterial chemoembolization (TACE), liver transplantation, and/or RT. RT was conducted to adrenal lesions after their intrahepatic lesions were controlled more than 2 months. The parameters studied included survival rates and tumor responses to RT. The Kaplan-Meier method was used to evaluate survival rate and the Cox regression model was used to identify potential predictors of outcome. Results The patients treated by RT had adrenal metastasis on the right side (41), the left (6), or on both sides (8). In all 55 patients, the median survival duration was 13.6 months and there was 100% pain relief after completion of RT. Adverse effects were mild to moderate. Unfavorable pretreatment predictors determined by univariate analysis were associated with multiple intrahepatic foci, metastases to additional organs, high γ-glutamyltransferase and alpha-fetoprotein levels, liver function of Child-Pugh classification B and uncontrolled primary HCC. By multivariate analysis, unfavorable predictors were multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC. Conclusions Radiotherapy as treatment for adrenal metastases in HCC is a good palliative therapy that is associated with reasonable safety. It appears reasonable that such patients should be considered to be treated with radiotherapy. Multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC were unfavorable predictors.

Cervical carcinoma is the second most prevalent type of malignancy in females worldwide. The crucial etiological factors involved in the development of cervical carcinoma include infection with the papillomavirus, and the structural or functional mutation of oncogenes and tumor suppressor genes. CD44 refers to a multifunctional family of type I transmembrane proteins. These proteins have been implicated in numerous biological processes, including cell adhesion, cell migration and metastasis. The present study examined the differences in the expression levels of ATP-binding cassette sub-family G member 2, CD24, CD44, CD133, cytokeratin (CK) 14 and CK19 between cervical cancer tissues and corresponding normal non-tumor tissues by flow cytometry. Then, the CD44+ or CD44‑ cells from cervical cancer tissues were sorted for identification and confirmation of differential expression by flow cytometry. The results demonstrated that the expression level of CD44 in cervical cancer tissues was higher than in the corresponding non-tumor normal tissues (t=3.12; P=0.0102). Compared with the CD44‑ cells, the FOS-like antigen 1 (Fra-1), nestin, nuclear receptor subfamily 4, group A, member 2, OCT4 and p63 genes were highly expressed in CD44+ cells. The fold changes were 3.55, 3.55, 2.46, 2.87 and 2.56, respectively (P

The aim of the present study was to examine the effects of activated hepatic stellate cells (HSCs) and their paracrine secretions, on hepatocellular cancer cell growth and gene expression in vitro and in vivo. Differentially expressed genes in McA-RH7777 hepatocellular carcinoma (HCC) cells following non-contact co-culture with activated stellate cells, were identified by a cDNA microarray. The effect of the co-injection of HCC cells and activated HSCs on tumor size in rats was also investigated. Non-contact co-culture altered the expression of 573 HCC genes by >2-fold of the control levels. Among the six selected genes, ELISA revealed increased protein levels of hepatic growth factor, matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9). Incubation of HCC cells with medium conditioned by activated HSCs significantly increased the proliferation rate (P

The purpose of this work is to assess a fast technique that measures tissue stiffness and temperature during focused ultrasound thermal therapy (FUS). A one-dimensional (1D) MR elastography (MRE) pulse sequence was evaluated for the purpose of obtaining rapid measurements of thermally induced changes in tissue stiffness and temperature for monitoring FUS treatments. The accuracy of the 1D measurement was studied by comparing tissue displacements measured by 1D MRE with those measured by the well-established 2D MRE pulse sequence. The reproducibility of the 1D MRE measurement was assessed, in gel phantoms and ex vivo porcine tissue, for varied FUS intensity levels (31.5-199.9 W cm(-2)) and over a range of displacements at the focus (0.1-1 microm). Temperature elevations in agarose gel phantoms were measured using 1D MRE and calibrated using fiberoptic-thermometer-based measurements. The 1D MRE displacement measurements are highly correlated with those obtained with the 2D technique (R(2) = 0.88-0.93), indicating that 1D MRE can successfully measure tissue displacement. Ten repeated trials at each FUS power level yielded a minimum detectable displacement change of 0.2 microm in phantoms and 0.4 microm in tissue (at 95% confidence level). The 1D MRE temperature measurements correlated well with temperature changes measured simultaneously with fiberoptic thermometers (R(2) = 0.97). The 1D MRE technique is capable of detecting tissue displacements as low as 0.4 microm, which is an order of magnitude smaller than 5 microm displacements expected during FUS therapy (Le et al 2005 AIP Conf. Proc.: Ther. Ultrasound 829 186-90). Additionally, 1D MRE was shown to provide adequate measurements of temperature elevations in tissue. These findings indicate that 1D MRE may be an effective tool for monitoring FUS treatments.

Primary pulmonary paraganglioma is a rare disease. We report a case of a 37-year old female patient with space-occupying lesions in the right lower pulmonary lobe during a routine examination without any symptoms. The patient underwent video-assisted thoracoscopic surgery (VATS) resection of the right middle lobe and dissection of hilar and mediastinal lymph nodes under general anesthesia. She recovered without recrudescence. Preoperative diagnosis is difficult. Accurate diagnosis requires pathological examination, and immunohistochemical test is particularly important. Complete resection is the first treatment option for solitary primary pulmonary paraganglioma; however, VATS is a better technique. Given the high local control rates and few complications of radiotherapy, it is considered as a standard treatment.

Purpose/Objective(s): Radiotherapy (RT) has been and continues to be a mainstay of treatment for locally advanced or medically inoperable hepatocelluar carcinoma. The major limitation to radiotherapy for intrahepatic tumors is radiation-induced liver disease (RILD). Hepatic non-parenchymal cells (NPCs) play an important role in RILD. This study is to determine whether irradiated hepatic NPCs could influence hepatic parenchymal cells’s radio-sensitivity and its possible machanisms. Materials/Methods: NPCs, isolated from Sprague-Dawley rats’ livers, were cultured in DMEM supplemented with 10% fetal bovine serum for 72 hours. Then cells were placed in Williams E medium(free of serum), followed by irradiation (10Gy/1F) or un-irradiation. The supernatants were collected, respectively. Rat cytokine antibody arrays (RayBio® Rat Cytokine Antibody Array, Detect 90 rat cytokines,RayBiotech, Inc.) were tested. Supernatants from irradiated and un-irradiated NPCs were added to each irradiated rats’ hepatocytes (10Gy/1F), respectively. After incubation 24 hours, apoptosis of hepatocytes were detected with FCM using Annexin-V and propidium iodide (PI) double staining. Results: In comparison of un-irradiated NPCs’ supernatant, expression of IL-3, IL-6, IL-10, MMP-8, RAGE, RALT/MIG-6, RELM beta, Resistin, TNF-α were significantly up-regulated, and expression of BDNF, β-Catenin, basic-FGF, β-NGF, CNTF, CNTF Rα, Insulin, Leptin, LIX, TGF-β1, TGF-β3, TIE-2 were down-regulated in irradiated NPCs’ supernatants. Apoptosis of hepatocytes cultured in the supernatants of irradiated NPCs was 38%, however, apoptosis was only 21% in those with un-irradiated NPCs. The difference is significant between the two groups (P