Macroscopic Heterostructure Membrane of Graphene Oxide/Porous Graphene/Graphene Oxide for Selective Separation of Deuterium Water from Natural Water.

Deuterium water (D2 O) is a strategic material that is widely used in and scientific research and has applications in fields such as nuclear energy generation. However, its content in natural water is extremely low. Therefore, the development of a room-temperature technology for achieving simple, efficient, and low-cost separation of D2 O from natural water is challenging. In this study, porous graphene (PG) nanosheets with "crater-like" pores are sandwiched between two layers of graphene oxide (GO) membranes to prepare a GO/PG/GO membrane with a macroscopic heterostructure, which can be used to separate D2 O and H2 O by pressure-driven filtration. At 25 °C, the rejection rate of D2 O is ≈97%, the selectivity of H2 O/D2 O is ≈35.2, and the excellent performance can be attributed to the difference of transmembrane resistance and flow state of H2 O and D2 O in the confinement state. In addition, the D2 O concentration in natural water is successfully enriched from 0.013% to 0.059% using only one stage, and the membrane exhibits excellent structural and cycling stability. Therefore, this method does not require ultralow temperatures, high energy supplies, complex separation equipment, or the introduction of toxic chemicals. Thus, it can be directly applied to the large-scale industrial production and removal of D2 O.

Pancreatic cancer incidence and mortality patterns in 2006-2015 and prediction of the epidemiological trend to 2025 in China.

BACKGROUND: Due to dietary patterns, the aging population, and other high-risk factors, the occurrence of pancreatic cancer (PC) has been rapidly increasing in China. AIM: To present the epidemiological trends of PC in China over the past decade and the estimated trend in 2025 and to compare the international differences in PC morbidity and mortality. METHODS: This study used a series of nationally representative data from the National Central Cancer Registry of China (NCCR), the International Agency for Research on Cancer and the Institute for Health Metrics and Evaluation databases. Age-standardized data of the PC incidence and mortality from 2006 to 2015 in China were extracted from the NCCR database. Linear regression models were used to estimate the incidence and mortality rates of PC in 2025. RESULTS: The age-standardized rates of PC in China increased from 3.65 per 100000 in 2006 to 4.31 per 100000 in 2015 and were estimated to reach up to 5.52 per 100000 in 2025. The mortality went from 3.35 per 100000 in 2006 to 3.78 per 100000 in 2015, estimated to reach up to 4.6 per 100000 in 2025. The number of new cases and deaths was low before 45 years and the peak age of onset was 85-89 years. The incidence and mortality rates in men were higher than those in women regardless of the region in China. In addition, the incidence and mortality rates in China were higher than the average level around the world. Likewise, disability-adjusted life years attributed to PC in China were 197.22 years per 100000, above the average level around the world. CONCLUSION: This study presented an increasing trend of PC in China and differences in morbidity, mortality and disability-adjusted life years between Chinese and global populations. Efforts need to be made to decrease the PC incidence and improve patient outcomes.

Novel Pathogenic Mutation of PNPLA1 Identified in Autosomal Recessive Congenital Ichthyosis: A Case Report.

Autosomal recessive congenital ichthyosis (ARCI) is characterized by being born as collodion babies, hyperkeratosis, and skin scaling. We described a collodion baby at birth with mild ectropion, eclabium, and syndactyly. Whole exome sequencing showed a compound heterozygous variant c.[56C>A], p.(Ser19X) and c.[100G>A], p.(Ala34Thr) in the PNPLA1 gene [NM_001145717; exon 1]. The protein encoded by PNPLA1 acts as a unique transacylase that specifically transfers linoleic acid from triglyceride to ω-hydroxy fatty acid in ceramide, thus giving rise to ω-O-acylceramide, a particular class of sphingolipids that is essential for skin barrier function. The variant was located in the patatin core domain of PNPLA1 and resulted in a truncated protein which could disrupt the function of the protein. This case report highlights a novel compound heterozygous mutation in PNPLA1 identified in a Chinese child.

Encapsulating peritoneal sclerosis in an AMA-M2 positive patient: A case report.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is hard to diagnose because of nonspecific symptoms and signs. It is a general consensus that EPS is classified as primary and secondary. There have been several studies discovering some high-risk factors such as liver cirrhosis, of which AMA-M2 is a biomarker, and intra-abdominal surgery such as laparoscopic surgery. Imaging studies help to diagnose EPS and exploratory laparotomy might be an alternative if imaging fails. Nowadays, laparotomy plays a key role in treating EPS, especially when medical treatments do not work and medical therapy fails to ease patients' symptoms. CASE SUMMARY: A 58-year-old man complained of unexplained vomiting and abdominal distension 2 mo after laparoscopic cholecystectomy. Increased alkaline phosphatase and liver enzymes were discovered. An autoimmune liver disease test showed that AMA-M2 was positive. A gastroscopy revealed bile reflux gastritis. A magnetic resonance imaging scan showed a slight dilatation of the intrahepatic bile duct. A colonoscopy showed that there was a mucosal eminence lesion in the sigmoid colon (24 cm away from the anus), with a size of 3 cm × 3 cm and erosive surface. At last, the small intestine and the stomach were found to be encased in a cocoon-like membrane during the surgery. The membrane was dissected and adhesiolysis was done to release the trapped organs. The patient recovered and was discharged 44 d after the operation, and there was no recurrence during a follow-up period of 3 mo. CONCLUSION: AMA-M2 is a marker of primary biliary sclerosis and may help to make a preoperative diagnosis of EPS.

Early-life gut microbial colonization shapes Th1/Th2 balance in asthma model in BALB/c mice.

BACKGROUND: We aimed to investigate the effect of early-life diverse microbial exposures on gut microbial colonization in an OVA-induced asthma model in BALB/c mice. METHODS: BALB/c mice were divided into 4 groups: A, offsprings were kept in a SPF environment during fetal, lactation, and childhood periods; B, offsprings were kept in the SPF environment during fetal and lactation periods, and kept in the general environment during childhood; C, offsprings were kept in the SPF environment only during fetal period, and then kept in the general environment; and D, offsprings were kept in the general environment during whole periods. The diversity of intestinal flora was analyzed using denaturing gradient gel electrophoresis. Mice were sensitized with OVA to establish an animal model of asthma. Then asthma-related inflammatory cytokines and histological analysis were performed. RESULTS: The diversity of intestinal microflora in group D was significantly higher than groups A, B and C at three days and three weeks after birth, and the diversity of intestinal microflora in groups C and D were significantly higher than groups A and B at five weeks after birth. The pathologic scores of OVA-induced asthmatic mice in group D were significantly lower than group A, and serum IFN-γ levels and the IFN-γ/IL-4 ratio in group D were significantly higher than group A. CONCLUSIONS: Exposure to diverse microbial environments in early life affects gut microbial colonization in BALB/c mice. The diversity of the intestinal flora in early life may prevent airway inflammation in asthma via regulating the Th1/Th2 balance.

Application effect of extensively hydrolyzed milk protein formula and follow-up in preterm children with a gestational age of less than 34 weeks: study protocol for a randomized controlled trial.

BACKGROUND: The average incidence of preterm birth in the world is up to 11.1 %, and deaths of preterm children account for more than 50 % of neonatal deaths. Gastrointestinal function of preterm children with a gestational age less than 34 weeks is immaturely developed. For preterm children who can only be fed with formula due to their mothers' sickness, choosing a suitable formula can not only meet the high nutritional needs of preterm children, but also solve their low gastrointestinal tolerability, and is thus very important. METHODS/DESIGN: The study is a prospective, randomized, single-blind and controlled clinical trial. Preterm children with a gestational age less than 34 weeks meeting the inclusion criteria who cannot be breastfed will be included. To demonstrate the application effect of extensively hydrolyzed milk protein formula on the target population, preterm children will be randomized into two groups, 185 subjects in each group. The observation group will be fed with extensively hydrolyzed milk protein (100 % whey protein) formula, while the control group will be fed with preterm children's formula until the children are discharged from the neonatal intensive care unit (NICU). All the formula involved in this study will be from Dumex. After discharge, both groups will be uniformly fed with formula for 0 to 6-month-old infants. For statistical analysis, a chi-square test and Student's t test will be applied using SAS 9.4. DISCUSSION: This will be the first randomized controlled clinical study with long-term observation of the growth and development of preterm children during the NICU stay and at 3-month follow-up after discharge from the NICU. Results from this study will be used to determine whether the extensively hydrolyzed formula is more suitable for the low gastrointestinal tolerability of preterm children, and also whether feeding preterm children who are fed with such formula during the NICU stay with ordinary infant formula after discharge from the NICU would affect the normal growth and development of preterm children in the early stage of their lives. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ) with number ChiCTR-IOR-14005696 , on December 22, 2014.

Establishment and characterization of GCSR1, a multi-drug resistant signet ring cell gastric cancer cell line.

Signet ring cell gastric cancer (SRCGC) has very poor prognosis worldwide, and studying its molecular characteristics is urgent for improving the outcome. However, few well-characterized SRCGC cell lines are available for research. Therefore, we established a novel cell line GCSR1, from a Chinese male SRCGC patient. Cell morphology of GCSR1 in culture, maintained in vitro for over 90 passages, is similar to the cells from the patient. GCSR1 cells proliferated in vitro with a doubling time of 67.65 h. Karyotyping showed they were aneuploid. Missense mutation occurred in codon 193 of P53 and deletion occurred in exons 1 and 3 of P16. Results of CCK8 assay revealed that GCSR1 was more resistant to 5-fluorouracil (5-FU) and mitomycin (MMC) than other gastric cancer cell lines. Stem cell marker assay by flow cytometry showed that GCSR1 had high proportion of CD44+ and/or CD133+ cells. It formed colonies easily in soft agar and generated xenograft tumors in nude mice. In conclusion, GCSR1 is a well-established, well-characterized multi-drug resistant cell line with abundant cancer stem cells.

Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis.

AIM: To investigate the efficacy of adding prokinetics to proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD). METHODS: PubMed, Cochrane Library, and Web of Knowledge databases (prior to October 2013) were systematically searched for randomized controlled trials (RCTs) that compared therapeutic efficacy of PPI alone (single therapy) or PPI plus prokinetics (combined therapy) for GERD. The primary outcome of those selected trials was complete or partial relief of non-erosive reflux disease symptoms or mucosal healing in erosive reflux esophagitis. Using the test of heterogeneity, we established a fixed or random effects model where the risk ratio was the primary readout for measuring efficacy. RESULTS: Twelve RCTs including 2403 patients in total were enrolled in this study. Combined therapy was not associated with significant relief of symptoms or alterations in endoscopic response relative to single therapy (95%CI: 1.0-1.2, P = 0.05; 95%CI: 0.66-2.61, P = 0.44). However, combined therapy was associated with a greater symptom score change (95%CI: 2.14-3.02, P < 0.00001). Although there was a reduction in the number of reflux episodes in GERD [95%CI: -5.96-(-1.78), P = 0.0003] with the combined therapy, there was no significant effect on acid exposure time (95%CI: -0.37-0.60, P = 0.65). The proportion of patients with adverse effects undergoing combined therapy was significantly higher than for PPI therapy alone (95%CI: 1.06-1.36, P = 0.005) when the difference between 5-HT receptor agonist and PPI combined therapy and single therapy (95%CI: 0.84-1.39, P = 0.53) was excluded. CONCLUSION: Combined therapy may partially improve patient quality of life, but has no significant effect on symptom or endoscopic response of GERD.

Differential expression of miR-195 in esophageal squamous cell carcinoma and miR-195 expression inhibits tumor cell proliferation and invasion by targeting of Cdc42.

MicroRNAs (miRNA) have played an important role in carcinogenesis. In this study, Agilent miRNA microarray was used to identify differentially expressed miRNAs in esophageal squamous cell carcinoma (ESCC) tissues and miR-195 was downregulated in ESCC compared with normal esophageal tissues. Moreover, Cdc42 was confirmed as target gene of miR-195. Ectopic expression of miR-195 in ESCC cells significantly downregulated Cdc42 by directly binding its 3' untranslated regions, and induced G1 cell cycle arrest, leading to a significant decrease in cell growth, migration, and invasion in vitro. Therefore, our findings demonstrated that miR-195 may act as a tumor suppressor in ESCC by targeting Cdc42.

Heterogeneity of chemosensitivity in esophageal cancer using ATP-tumor chemosensitivity assay.

AIM: Current chemotherapy for esophageal cancer is conducted on the basis of empirical information from clinical trials, which fails to take into account the known heterogeneity of chemosensitivity between patients. This study was aimed to demonstrate the degree of heterogeneity of chemosensitivity in esophageal cancers. METHODS: A total of 42 esophageal cancer specimens were collected. The heterogeneity of chemosensitivity in esophageal cancer specimens was examined using an ex vivo ATP-tumor chemosensitivity assay (ATP-TCA). RESULTS: Thirty eight specimens produced evaluable results (90.5%). The most active single agent tested was nedaplatin, to which 28.9% of samples were sensitive. Combinations of chemotherapy agents exhibited much higher sensitivity: cisplatin + paclitaxel was sensitive in 16 of 38 (42.1%) of samples, while nedaplatin+paclitaxel was more effective, which was sensitive in 20 of 38 cases (52.6%). CONCLUSION: There was a marked heterogeneity of chemosensitivity in esophageal cancer. Chemosensitivity testing may provide a practical method for testing new regimens before clinical trials in esophageal cancer patients.

[Prevention of restenosis with a new modified fully-covered retrievable esophageal stent].

OBJECTIVE: To observe and evaluate the effectiveness of a new modified fully-covered retrievable esophageal stent in preventing restenosis at the proximal end of the stent. METHODS: From January 2008 to October 2011, 380 consecutive patients who underwent placement of a conventional stent or a new modified stent for benign or malignant dysphagia were divided into two groups: conventional stent group 193 patients (male 137, female 56) and modified stent group 187 patients (male 125, female 62). The granulation formation and restenosis rate one month after stenting were evaluated. Data such as patient demographics, outcomes and complications were collected. The results were statistically analyzed by Student t test, chi-squared test, Fisher's exact probability or rank sum test. A P-value less than 0.05 was considered statistically significant. RESULTS: All stents were successfully implanted. They were highly effective in palliating dysphagia. The dysphagia score decreased from 3 (1) to 0 (1) in conventional stent group (P < 0.01), and that from 4 (1) to 0 (1) in modified stent group (P < 0.01). The modified stent group were superior to the conventional stent group in severe granulation formation rate (0 vs 4.7% (9/193), P = 0.004) and restenosis rate (2.7% (5/187) vs 7.3% (14/193), P = 0.041) within one month after stenting, and the modified stent was easier to retrieve. Postoperative remission rate of dysphagia, and complications such as chest pain, bleeding, perforation, stent migration had no statistical differences between the two groups (all P > 0.05). CONCLUSIONS: The new modified fully-covered retrievable esophageal stent can significantly reduce granulation formation at the proximal end of the stent. Using of this stent seems to be a better choice in treating patient of dysphagia, with lower restenosis rate and easier to retrieve.

[Advances in the molecular pathogenesis of hypertrophic cardiomyopathy].

Hypertrophic Cardiomyopathy (HCM) is a primary cardiac disorder characterized by asymmetric thickening of the septum and left ventricular wall. HCM affects 1 in 500 individuals in the general population, and it is the most common cause of sudden death in the young and athletes. The clinic phenotype of HCM is highly variable with respect to age at onset, degree of symptoms, and risk of sudden death. HCM is usually inherited as a Mendelian autosomal dominant trait. To date, over 900 mutations have been reported in HCM, which were mainly located in 13 genes encoding cardiac sarcomere protein, e.g., MYH7, MYBPC3, and TnT. In addition, more and more mitochondrial DNA mutations were reported to be associated with the pathogenesis of HCM. Based on the description of the clinical phenotype and morphological characteristics, this review focuses on the research in the molecular pathogenic mechanism of HCM and its recent advances.

Difference of gene expression profiles between esophageal carcinoma and its pericancerous epithelium by gene chip.

AIM: To study the difference of gene expression between esophageal carcinoma and its pericancerous epithelium and to screen novel associated genes in the early stage of esophageal carcinogenesis by cDNA microarray. METHODS: Total RNA was extracted with the original single step way from esophageal carcinoma, its pericancerous epithelial tissue and normal esophageal epithelium far from the tumor. The cDNA retro-transcribed from equal quantity of mRNA was labeled with Cy5 and Cy3 fluorescence functioning as probes. The mixed probes were hybridized with two pieces of BioDoor 4 096 double dot human whole gene chip. Fluorescence signals were scanned by ScanArray 3 000 laser scanner and farther analyzed by ImaGene 3.0 software with the digital computer. RESULTS: (1) A total of 135 genes were screened out, in which 85 and 50 genes whose the gene expression levels (fluorescence intensity) in esophageal carcinoma were more than 2 times and less than 0.5 times respectively compared with the normal esophageal epithelium. (2) There were also total 31 genes, among then 27 and 4 whose expressions in pericancerous tissue were 2-fold up-regulated and 0.5-fold down-regulated respectively compared with normal esophageal epithelium. (3) There were 13 genes appeared simultaneously in both pericancerous epithelium and esophageal carcinoma, while another 18 genes existed in pericancerous epithelium only. CONCLUSION: With the parallel comparison among these three gene profiles, it was shown that (1). A total of 135 genes, Whose expression difference manifested as fluorescence intensity were more than 2 times between esophageal carcinoma and normal esophageal epithelium, were probably related to the occurrence and development of the esophageal carcinoma. (2). The 31 genes showing expression difference more than 2 times between pericancerous and normal esophageal epithelium might be relate to the promotion of esophageal pericancerosis and its progress. The present study illustrated that by using the gene chip to detect the difference of gene expression profiles might be of benefit to the gene diagnosis, treatment and prevention of esophageal carcinoma.