Hepatic Artery Infusion Chemotherapy Sequential Hepatic Artery Embolization Combined with Operation in the Treatment of Recurrent Massive Hepatocellular Carcinoma Achieved Pathological Complete Response: A Case Report.

Hepatocellular carcinoma (HCC) recurrence, which encompasses both true recurrence resulting from cancer spread and de novo tumors developing within the same cancer-prone liver, presents a complication in approximately 70% of cases within a 5-year timeframe. The efficacy of neoadjuvant therapy for recurrence after hepatectomy for hepatocellular carcinoma is still unclear. We report a case of recurrent massive advanced hepatocellular carcinoma with pathological complete remission was treated by continuous hepatic arterial infusion chemotherapy (HAIC) and sequential transcatheter arterial embolization (TAE) combined with secondary operation. One month after resection, the patient recurred (massive type 141mm×76mm). After 4 times of HAIC sequential TAE conversion therapy, the tumor shrank significantly (70mm×29mm), alpha-fetoprotein(AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels decreased significantly, residual liver volume[left half liver accounted for 39.85% of standard liver volume(left half liver + right anterior lobe) accounted for 80.17% of standard liver volume] and Indocyanine green 15-minute retention(ICG R15 8.0%) complies with surgical requirement.The second operation was performed, and the tumor was completely resected after hepatic blood flow occlusion Requirement. The postoperative pathological results showed complete remission (PCR) of the tumor, and no recurrence was found during the follow-up of 16 months. In this case, HAIC sequential TAE conversion therapy has good short-term effect on patients with postoperative recurrence of hepatocellular carcinoma, tumor burden is significantly reduced, the second surgery pathology achieves complete remission, safety and tolerance, it is worthy of study and promotion.

Massive Hepatocellular Carcinoma with Situs Inversus Totalis Achieved a Complete Response Following Camrelizumab Plus Apatinib and Combined with Two-Stage Hepatectomy: A Case Report.

Situs inversus totalis (SIT) is a rare congenital condition in which abdominal and thoracic organs are transposed from normal positions. Two-stage hepatectomy (TSH) combined with translational therapy for hepatocellular carcinoma (HCC) with SIT has been rarely reported. We report a 41-year-old man with giant hepatocellular carcinoma (71 mm × 55 mm × 51 mm) whose future residual liver (FLR) and standard liver volume (SLV) ratio at first diagnosis was 37.4%. Preoperative volume assessment of portal vein ligation (PVL) revealed inadequate hypertrophy of FLR. After a multidisciplinary group discussion (MDT), the patient decided to follow conversion therapy. Three months later, ratio of the FLR/SLV increased from 37.4% to 71% after operation, which met the surgical requirements. Second hepatectomy, right lobectomy was successful. There was no recurrence after six months of follow-up. In our case, conversion therapy appears to be effective in maintaining residual liver hyperplasia, reducing tumor load, and preventing tumor progression in patients with large HCC during TSH.

Dispersion and weak retardation performance of sulfate-based starch maleic acid monoesters in cement.

To reduce the influence of a sulfate-based starch water-reducing agent on the setting time of cement, a novel starch-based water-reducing agent, namely sulfate-based starch maleic acid monoester (SAMAS), was designed to adjust its hydrophilicity by maleic acid monoester. Gel permeation chromatography, Fourier transform infrared spectroscopy, and 1H NMR nuclear magnetic resonance spectroscopy were used to characterize the prepared SAMAS, while Zeta potential, UV-Vis absorption, X-ray photoelectron spectroscopy, X-ray diffraction, cement paste fluidity, and setting time measurements were conducted to investigate its dispersion performance, retardation performance, adsorption behavior, and mechanism of action. SAMAS exhibited good dispersion performance and did not significantly prolong the setting time of the cement. In addition, the dispersion performance of SAMAS was found to depend mainly on steric hindrance, and its weak retardation performance originated from the hydrophilic regulation of the maleic acid monoester groups, which ensures the normal progress of the cement hydration reaction by hindering the formation of a hydration film.

The Effects of Different Doses of Alfentanil and Dexmedetomidine on Prevention of Emergence Agitation in Pediatric Tonsillectomy and Adenoidectomy Surgery.

Background: Emergence agitation (EA) is a common problem often observed in children after sevoflurane anesthesia, which can be prevented by dexmedetomidine and alfentanil. This study aims to compare the effectiveness of dexmedetomidine alone and with different doses of alfentanil in preventing EA in children under sevoflurane anesthesia. Materials and Methods: In a double-blind trial, 80 children (ASA I or II, 3-7 years old) undergoing tonsillectomy alone and adenotonsillectomy with sevoflurane anesthesia were randomly assigned into four groups: the control group, dexmedetomidine (DEX) group, dexmedetomidine plus 10 µg/kg alfentanil group (DEX + Alf1), and dexmedetomidine plus 20 µg/kg alfentanil group (DEX + ALf2). The incidence of EA was assessed with the Aono's scale, and the severity of EA was evaluated with the Pediatric Anesthesia Emergence Delirium (PAED) scale. The time of tracheal extubation and time of wake were recorded. Postoperative pain and complications such as nausea and vomiting, cough, laryngospasm, and bradycardia were recorded. Results: The incidence of EA was 50% in the control group, 25% in the DEX group, and 5% in the DEX + Alf1 group, and it never happened in the DEX + Alf2 group. The Aono's scale, the PAED scale, and the FLACC scale in the control group and the DEX group were significantly more than those in the DEX + Alf1 group and the DEX + Alf2 group after the tracheal extubation (p < 0.05). The time of tracheal extubation of the control group and the DEX group were significantly shorter than those in the DEX + Alf1 group and the DEX + Alf2 group (p < 0.05). The awakening time of the DEX + Alf2 group is significantly longer than those in other groups (p < 0.05). The case of postoperative nausea and vomiting in the DEX + Alf1 group was fewer than those in the other groups (p < 0.05). And, the cases of cough and laryngospasm and bronchospasm in the DEX + Alf1 group and the DEX + Alf2 group were significantly less than those in the control group and the DEX group after the tracheal extubation (p < 0.05). Conclusion: The combined administration of alfentanil and dexmedetomidine can reduce EA in children undergoing tonsillectomy alone and adenotonsillectomy with sevoflurane anesthesia. Dexmedetomidine plus 10 µg/kg alfentanil seems to be more appropriate than other dose combinations as it reduced EA and postoperative nausea and vomiting but did not prolong the time to awake.

Wide-band high-resolution synthetic imaging of a segmented large-scaled lightweight diffractive telescope.

In this Letter, we report a segmented large-scaled lightweight diffractive telescope testbed newly built in our laboratory. The telescope, consisting of one 710-mm-diameter element in the center surrounded by eight 352-mm-diameter elements and a smaller eyepiece of achromatic lenses, can realize wide-band high-resolution imaging of 0.55-0.65 µm. The stitching errors are coarsely corrected by adjusting the motion stage mounted on each element. In particular, an optical synthesis system inserted behind the eyepiece is designed to compensate the residual tip-tilt-piston errors. We present the experimental imaging result of two stitched elements, which is the first successful experimental verification obtained by a practical segmented diffractive telescope to enhance the resolution. Moreover, spatial modulation diversity technology is used to restore the synthetic image so as to improve its quality and contrast.

Adaptive piston correction of sparse aperture systems with stochastic parallel gradient descent algorithm.

A phased sparse aperture system provides an economic solution to get high resolution images with less volume and weight. The crucial point of such systems is adaptive correction of piston, that is, a close-loop control aiming at stabilizing the optical path differences within a fraction of the wavelength. In this paper, we present an autonomous phasing approach using stochastic parallel gradient descent algorithm through optimization of image quality. The synthetic system can be phased by iteratively commanding piston actuators without any additional optics. Simulations are first performed to test the validity. Then experimental results based on a binocular telescope testbed are presented, showing that our proposed close-loop control of piston correction doesn't only work with both laser and white-light point sources, but also with an extended object.

Optical sparse aperture imaging with faint objects using improved spatial modulation diversity.

The next generation of optical sparse aperture systems will provide high angular resolution for astronomical observations. Spatial modulation diversity (SMD) is a newly developed post-processing technique for such telescopes, faced with challenges of imaging faint objects, which are very attractive for astronomers but always make raw diversity images suffer serious photon noise. In this paper, we propose an improved SMD with denoising reprocessing embedded to address the problem. The blocking-matching and 3D filtering algorithm, a state-of-the-art denoising technique, is first employed to process the diversity images with low photon intensities generated by spatial modulation, specifically switching off each sub-aperture sequentially. SMD algorithm then can be applied to estimate wavefront and digitally restore images. It is demonstrated by both simulations and experiments that the proposed method outperforms the previous SMD in terms of reconstructions of wavefront and imagery from the raw images of faint objects corrupted seriously by photon noise. The reported method may provide an alternative approach to acquire high-quality images of faint objects for astronomical observations of the future segmented mirrors or telescope arrays.

Active sparse aperture imaging using independent transmitter modulation with improved incoherent Fourier ptychographic algorithm.

Optical sparse aperture imaging shows great promise for the next generation of high resolution systems. In this paper, we propose and demonstrate an active sparse aperture imaging approach using independent transmitter modulation to digitally overcome phasing errors, correct aberrations, and further improve resolution. The reported imaging scheme consists of a general sparse aperture system and an active illumination unit, specifically an independent pattern projector. A series of raw images are captured with the projector scanned to illuminate the object. Based on the acquired data set, the improved incoherent Fourier ptychographic algorithm is utilized to reconstruct sparse aperture images with distortions removed and contrast enhanced. Furthermore, thanks to illumination pattern modulation, higher resolution beyond the diffraction limit of the synthetic aperture system is gained as a benefit. Good-quality and higher-resolution sparse aperture imagery obtained by employing our proposed technique in both simulation and experiment demonstrates the effectiveness. The reported approach may provide new insights to address the phasing and image restoration problems of sparse aperture systems in the transmitting path rather than only in the receiving path.

Elevated tissue Cr levels, increased plasma oxidative markers, and global hypomethylation of blood DNA in male Sprague-Dawley rats exposed to potassium dichromate in drinking water.

Hexavalent chromium [Cr (VI)] is prevalent in ground water in some areas, but evidence on the toxic effects of Cr (VI) via ingestion through drinking water remains insufficient. The aims of our study were to investigate the toxic effects of Cr (VI) through oral water ingestion on oxidative stress and DNA methylation. Thirty-two Sprague-Dawley rats were randomly divided into four groups, and exposed to porassium dichromate (K2 Cr2 O7 ; 0, 30, 100, and 300 mg/L) in drinking water for 4 weeks. Mean body weight gain, mean water consumption, clinical chemistry determinations, and oxidative stress levels in plasma were measured. Global DNA methylation changes and DNA methylation status at the promoter of p16 gene were also detected. After 4 weeks, mild anemic effects and increased plasma malondialdehyde (MDA) levels occurred in rats exposed to 100 mg/L or 300 mg/L of Cr (VI). Plasma glutathione peroxidase (GSH-Px) activity decreased in all exposed groups. Global DNA methylation levels were reduced in 100 mg/L and 300 mg/L exposure groups. However, DNA methylation status at the promoter of P16 gene remained unchanged in all K2 Cr2 O7- treated groups. The correlation analysis indicated that increased MDA levels were closely correlated to global DNA hypomethylation. Our results indicated that oral ingestion of Cr (VI) through drinking water caused not only oxidative stress in plasma, but also global DNA hypomethylation in blood cells from male rats, and a good correlation was found between increased MDA levels and reduced global DNA methylation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1080-1090, 2016.

Transgenerational impaired male fertility with an Igf2 epigenetic defect in the rat are induced by the endocrine disruptor p,p'-DDE.

STUDY QUESTION: What are the epigenetic mechanisms underlying the transgenerational effect of p,p'-DDE on male fertility? SUMMARY ANSWER: Impaired male fertility with an Igf2 epigenetic defect is transgenerationally inherited upon exposure of p,p'-DDE. WHAT IS KNOWN ALREADY: p,p'-Dichlorodiphenoxydichloroethylene (p,p'-DDE) is one of the primary metabolite products of the ancestral organochlorine pesticide dichlorodiphenoxytrichloroethane. As it is a known anti-androgen endocrine disruptor, it could cause harmful effects on the male reproductive system. STUDY DESIGN, SIZE, DURATION: Pregnant rats (F0) were administered with p,p'-DDE or corn oil at the critical time of testis development, i.e. from gestation days 8 to 15. Male and female rats of the F1 generation were mated with each other to produce F2 progeny. To reveal whether the transgenerational phenotype is produced by the maternal or paternal line, F3 progeny were generated by intercrossing control (C) and treated (DDE) males and females of the F2 generation according to the following groups: (i) C♂-C♀, (ii) DDE♂-DDE♀, (iii) DDE♂-C♀ and (iv) C♂-DDE♀. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mature sperm and testes were collected from male offspring of the F1-F3 generations for the examination of male fertility parameters, i.e. sperm count and motility, testis histology and apoptosis. Expression of the imprinted genes, H19 and Igf2, was detected by real-time PCR. Igf2 DMR2 methylation was analyzed by bisulfite genomic sequencing. MAIN RESULTS AND THE ROLE OF CHANCE: Upon exposure of p,p'-DDE, the male F1 generation showed impaired male fertility and altered imprinted gene expression caused by Igf2 DMR2 hypomethylation. These defects were transferred to the F3 generation through the male germline. LIMITATIONS, REASONS FOR CAUTION: This study has examined the effect of p,p'-DDE only on the sperm number and motility and the possible mechanism of Igf2 DMR2 methylation in vivo and thus has some limitations. Further investigation is necessary to focus on the epigenetic effects of p,p'-DDE at the genome level and to include a more detailed semen quality analysis including sperm morphology assessment. WIDER IMPLICATIONS OF THE FINDINGS: Impaired male fertility with epigenetic alterations is transgenerationally inherited after environmental exposure of p,p'-DDE, posing significant implications in the etiology of male infertility. STUDY FUNDING/COMPETING INTERESTS: The present research was supported by National Natural Science Fund for Young Scholar (81102161), the Natural Science Fund of Zhejiang Province (LY14H260004) and funding from the Health Department of Zhejiang Province (201475777). No competing interests are declared.

Role of DNA methylation in cell cycle arrest induced by Cr (VI) in two cell lines.

Hexavalent chromium [Cr(IV)], a well-known industrial waste product and an environmental pollutant, is recognized as a human carcinogen. But its mechanisms of carcinogenicity remain unclear, and recent studies suggest that DNA methylation may play an important role in the carcinogenesis of Cr(IV). The aim of our study was to investigate the effects of Cr(IV) on cell cycle progress, global DNA methylation, and DNA methylation of p16 gene. A human B lymphoblastoid cell line and a human lung cell line A549 were exposed to 5-15 µM potassium dichromate or 1.25-5 µg/cm² lead chromate for 2-24 hours. Cell cycle was arrested at G1 phase by both compounds in 24 hours exposure group, but global hypomethylation occurred earlier than cell cycle arrest, and the hypomethylation status maintained for more than 20 hours. The mRNA expression of p16 was significantly up-regulated by Cr(IV), especially by potassium dichromate, and the mRNA expression of cyclin-dependent kinases (CDK4 and CDK6) was significantly down-regulated. But protein expression analysis showed very little change of p16 gene. Both qualitative and quantitative results showed that DNA methylation status of p16 remained unchanged. Collectively, our data suggested that global hypomethylation was possibly responsible for Cr(IV)-induced G1 phase arrest, but DNA methylation might not be related to up-regulation of p16 gene by Cr(IV).

DNA damage and oxidative stress in human B lymphoblastoid cells after combined exposure to hexavalent chromium and nickel compounds.

In the present study, human B lymphoblastoid cells were exposed to potassium dichromate and/or nickel chloride for 24h or 48h. The cell viability and DNA damage induced by these compounds was measured with the CCK-8 assay and Comet assay, respectively. In addition, the generation of reactive oxygen species (ROS) and the levels of malondialdehyde (MDA) were measured using commercially available kits. Our results indicated that potassium dichromate could decrease cell viability and induce DNA damage in human B lymphoblastoid cells in a time - and concentration - dependent manner, but the toxicity of nickel chloride was not so obvious at concentrations used in our study. The results of ROS showed that both two compounds could only induce weak elevation of ROS level, but MDA levels were significantly enhanced. Antagonistic effects of cytotoxicity were mainly found between Cr (VI) and Ni (II), and synergistic effects of DNA damage and oxidative stress were partially found between these two compounds. Moreover, there were good correlations between the results of comet assay and the results of oxidative stress assays. It is suggested that synergistic DNA damage induced by simultaneously exposure of hexavalent chromium and nickel compounds is possibly related to oxidative stress.

Chemokine (C-C motif) ligand 22 is down-regulated in a human B lymphoblastoid cell line by PCB153 and in residents from PCBs-contaminated areas.

Polychlorinated biphenyls (PCBs) are ubiquitous, persistent pollutants found in the environment and human tissues. Exposure to PCBs is of great concern to human health because they are known to cause neurological, reproductive, endocrinal, and other effects. The aim of the present study was to find some novel gene markers induced by PCBs through a combination of microarray screening followed by validating with quantitative real time PCR in vitro and in population investigation. In the present study, gene expression profiles of human B lymphoblastoid cells treated with different concentrations of non-coplanar 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) were analyzed using microarray. The differentially expressed genes were further confirmed by real-time PCR in vitro and in individuals from PCBs-contaminated sites. Our results indicated an overlap of 15 differentially expressed genes among samples treated with different concentrations of PCB153, and six of them were selected for validating with qRT-PCR. Two up-regulated genes (CCDC92 and TMEM175) and three down-regulated genes (CCL22, GZMK, and STK38L) were further confirmed by qRT-PCR in vitro. The expression levels of CCL22 in individuals from PCBs-contaminated sites were significantly (P<0.05) lower than those in controls. Therefore, CCL22 seems to be a sensitive gene marker induced by PCBs, although it needs to be confirmed by further studies with a larger number of subjects.

Thyroid endocrine dysregulation and erythrocyte DNA damage associated with PBDE exposure in juvenile crucian carp collected from an e-waste dismantling site in Zhejiang Province, China.

In the present study, 40 juvenile crucian carp (Carassius auratus) were caught from a river close to an electronic waste (e-waste) site (exposed group) and another located 80 km away from the e-waste site (control group) in Zhejiang, China. Results indicated that muscle levels of polybrominated diphenyl ethers (median PBDEs, 235.98 ng/g wet wt; range, 7.70-703.31 ng/g wet wt), serum levels of thyroid-stimulating hormone (median TSH, 2.32 µIU/ml; range, 2.05-2.72 µIU/ml) and erythrocyte DNA damage level (median Olive tail movement, 16.27 µm; range, 4.28-27.51 µm) were higher in the exposed group than those in the control group (0.56 ng/g wet wt, range, 0.34-1.24 ng/g wet wt, p < 0.01; 1.70 µIU/ml, range, 1.40-2.08 µIU/ ml, p < 0.01; 6.06 µm, range, 2.01-10.72 µm, p < 0.01, respectively). Thyroxine (T4) was significantly lower in the exposed group (8.97 µIU/ml) than in the control group (12.47 µIU/ml). In addition, thyroid endocrine disorder and erythrocyte DNA damage levels were significantly associated with polybrominated diphenyl ether exposure. Hence, PBDEs may affect wild fish populations in real ecosystems with thyroid endocrine disruption and DNA damage.

Levels of PCDD/Fs and DL-PCBs in selected foods and estimated dietary intake for the local residents of Luqiao and Yuhang in Zhejiang, China.

Polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) were measured by high resolution gas chromatograph/high resolution mass spectrometer (HRGC/HRMS) in six food groups from Luqiao (LQ) where the e-waste has been recycled and from Yuhang (YH) where the agriculture dominates in Zhejiang Province in China. The total WHO-TEQ values of PCDD/Fs and DL-PCBs in selected foods from LQ were significantly much higher than those from YH. The highest level of the total WHO-TEQ was in crucian carp (10.87 pg g(-1) w.w.) followed by duck (3.77 pg g(-1) w.w.), hen eggs (2.80 pg g(-1) w.w.), chicken (2.43 pg g(-1) w.w.), rice (0.08 pg g(-1) w.w.) and vegetables (0.022 pg g(-1) w.w.) in LQ. By contrast, the highest levels were measured in duck (0.74 pg g(-1) w.w.) followed by hen eggs (0.69 pg g(-1) w.w.), crucian carp (0.55 pg g(-1) w.w.), chicken (0.44 pg g(-1) w.w.), vegetables (0.002 pg g(-1) w.w.) and rice (0.0002 pg g(-1) w.w.) in YH, respectively. The monthly intake of PCDD/Fs and DL-PCBs for the local residents was 401.75 pg WHO-TEQ g(-1) w.w. in LQ, which is above the provisional tolerable monthly intake (PTMI) set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). We determined a monthly intake of 37.13 pg WHO-TEQ g(-1)w.w. in YH, which is below the PTMI. Crucian carp was the predominant contributor to the estimated monthly intake (EMI), accounting for 67.74% and 36.51% in LQ and YH, respectively. High levels of PCDD/Fs and DL-PCBs in selected foods indicate severe contamination of these pollutants in the e-waste recycling site.