A 47-Year-Old Man with Hyperphosphatemia Due to Chronic Renal Failure Treated with Lanthanum Carbonate Tablets Presenting Acutely with Partial Large Bowel Obstruction.

BACKGROUND Hyperphosphatemia is a complication of chronic renal failure (CRF) due to reduction in the glomerular filtration rate. Lanthanum carbonate is a commonly used phosphate binder for patients with CRF and hyperphosphatemia, but has adverse effects if patients are not monitored. This report is of a 47-year-old man with hyperphosphatemia due to CRF treated with lanthanum carbonate tablets who presented acutely with partial large bowel obstruction. The incidence of lanthanum carbonate causing intestinal obstruction is rare, and few cases in the literature have described the course of the disease in detail. CASE REPORT A 47-year-old man diagnosed with diabetic nephropathy underwent hemodialysis treatment and was prescribed 0.5 g/day of chewable lanthanum carbonate tablets. After taking lanthanum carbonate for 5 months, the patient experienced symptoms of decreased bowel movements and exhaustion, which progressively worsened. Abdominal computed tomography (CT) revealed multiple hyperdensities in the large bowel, indicating the presence of lanthanum deposition. Lanthanum carbonate was promptly discontinued. After undergoing enema and catharsis treatment, the large bowel obstruction was relieved, and the hyperdensities in the abdominal CT disappeared. The colonoscopy and histologic examination revealed ulcerations and inflammatory changes in the large bowel mucosa. CONCLUSIONS This report highlights the rare association between the use of lanthanum carbonate tablets and intestinal obstruction. Healthcare providers should enhance their vigilance regarding lanthanum carbonate-induced serious gastrointestinal adverse reactions and actively seek to detect lanthanum deposition by abdominal CT or radiography (X-ray). After the occurrence of lanthanum deposition, drug withdrawal and promotion of defecation are primary treatment methods.

High Child-Pugh and CRUB65 scores predict mortality of decompensated cirrhosis patients with COVID-19: A 23-center, retrospective study.

Background: COVID-19 has rapidly become a major health emergency worldwide. The characteristic, outcome, and risk factor of COVID-19 in patients with decompensated cirrhosis remain unclear.Methods: Medical records were collected from 23 Chinese hospitals. Patients with decompensated cirrhosis and age- and sex-matched non-liver disease patients were enrolled with 1:4 ratio using stratified sampling.Results: There were more comorbidities with higher Chalson Complication Index (p < 0.001), higher proportion of patients having gastrointestinal bleeding, jaundice, ascites, and diarrhea among those patients (p < 0.05) and in decompensated cirrhosis patients. Mortality (p < 0.05) and the proportion of severe ill (p < 0.001) were significantly high among those patients. Patients in severe ill subgroup had higher mortality (p < 0.001), MELD, and CRUB65 score but lower lymphocytes count. Besides, this subgroup had larger proportion of patients with abnormal (PT), activated partial thromboplatin time (APTT), D-Dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL) and Creatinine (Cr) (p < 0.05). Multivariate logistic regression for severity shown that MELD and CRUB65 score reached significance. Higher Child-Pugh and CRUB65 scores were found among non-survival cases and multivariate logistic regression further inferred risk factors for adverse outcome. Receiver Operating Characteristic (ROC) curves also provided remarkable demonstrations for the predictive ability of Child-Pugh and CRUB65 scores.Conclusions: COVID-19 patients with cirrhosis had larger proportion of more severely disease and higher mortality. MELD and CRUB65 score at hospital admission may predict COVID-19 severity while Child-Pugh and CRUB65 score were highly associated with non-survival among those patients.

A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients.

In this study, we aimed to evaluate the diagnostic value of serological assay for SARS-CoV-2. A newly-developed ELISA assay for IgM and IgG antibodies against N protein of SARS-CoV-2 was used to screen the serums of 238 admitted hospital patients between February 6 and February 14, 2020 with confirmed or suspected SARS-CoV-2. SARS-CoV-2 RNA was detected on pharyngeal swab specimens using real time RT-PCR. 194 (81.5%) of the serums were detected to be antibody (IgM and/or IgG) positive, significantly higher than the positive rate of viral RNA (64.3%). There was no difference in the positive rate of antibodies between the confirmed patients (83.0%, 127/153) and the suspected patients (78.8%, 67/85), whose nucleic acid tests were negative. The antibody positive rates were very low in the first five days after initial onset of symptoms, and then rapidly increased as the disease progressed. After 10 days, the antibody positive rates jumped from below 50% to over 80%. However, the positive rates of viral RNA maintained above 60% in the first 11 days after initial onset of symptoms, and then rapidly decreased. Overall, the suspected patients were most likely infected by SARS-CoV-2. Before the 11th day after initial onset of symptoms, nucleic acid test is key for confirmation of viral infection. The combination of serological assay can greatly improve the diagnostic efficacy. After the 11th day post-disease onset, the diagnosis for viral infection should be majorly dependent on serological assay.

Large-Area Stable Superhydrophobic Poly(dimethylsiloxane) Films Fabricated by Thermal Curing via a Chemically Etched Template.

Inspired by nature, large-area stable superhydrophobic poly(dimethylsiloxane) (PDMS) films have generated extensive interest for various applications such as self-cleaning, corrosion protection, liquid transport, optical services, and flexible electronics. However, the current methods used to prepare such films are difficult to apply for efficient large-area fabrication. In this article, an effective technique for fabricating low adhesive superhydrophobic films based on the use of a chemically etched template followed by a thermal curing process is introduced. On the basis of this approach, the importance of chemical solution concentration as well as etching time is discussed to outline the specific rules required for forming different surface topographies of the templates. Then, PDMS films with varying wettabilities can be fabricated in which one can achieve CA > 160° and SA < 10°. Finally, for engineering needs and actual preparation, large-area PDMS films are obtained via a roll-to-roll (R2R) process, which show a superhydrophobic property even after high-intensity friction and have excellent acid and alkaline resistance, UV resistance, and optical transparency. The prepared large-area stable superhydrophobic PDMS films have the potential to be used in the aerospace field in the future because of their excellent anti-icing performance.

MicroRNA-519a promotes proliferation and inhibits apoptosis of hepatocellular carcinoma cells by targeting FOXF2.

Recent studies report that microRNA-519a (miR-519a) is a novel oncomir, which facilitates the onset and progression of human cancers. However, the clinical significance of miR-519a and its functional role and underlying mechanisms in hepatocellular carcinoma (HCC) are poorly investigated. In the present study, elevated expression of miR-519a was observed in HCC tissues compared with adjacent non-tumor tissues. The increased level of miR-519a expression was significantly correlated with adverse clinical features of HCC including hepatitis B virus (HBV) infection, large tumor size, cirrhosis and advanced tumor-node-metastasis tumor stage. Furthermore, high expression of miR-519a was prominently associated with a poorer 5-year overall survival and recurrence-free survival of HCC patients. Gain- and loss-of function experiments showed that miR-519a overexpression enhanced proliferation and reduced apoptosis of Huh7 cells. By contrast, miR-519a knockdown inhibited SMMC-7721 cell proliferation and induced apoptosis. Importantly, up-regulation of miR-519a reduced the expression of FOXF2 mRNA and protein in Huh7 cells, while down-regulation of miR-519a resulted in increased expression of FOXF2 in SMMC-7721 cells. An inverse correlation between mRNA levels of miR-519a and FOXF2 was observed in HCC tissues. Thus, Forkhead box F2 (FOXF2) was identified as a downstream target of miR-519a in HCC. Mechanistically, the effects of miR-519a knockdown on SMMC-7721 cells were abrogated by FOXF2 repression. In conclusion, miR-519a is a novel prognostic predictor for HCC patients and it may potentiate proliferation and inhibits apoptosis of HCC cells by targeting FOXF2.

A two-microRNA signature as a potential biomarker for early gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumors worldwide. No fundamental improvements in the five-year survival rates of patients with GC have been reported due to a low early diagnosis rate. Therefore, the identification of novel biomarkers is urgently required for an early diagnosis of GC. A total of 86 patients were selected for the present study, including 44 patients with early stage GC (T1-T2 according to TNM staging criteria) and 42 normal gastric mucosa samples from non-cancer patients as controls. A total of 18 samples were used for the microRNA (miRNA) microarray experiments, including nine early GC and nine normal gastric mucosa samples. Bioinformatics algorithms, significant analysis of microarray (SAM), top scoring pair (TSP) and statistical receiver operating characteristic curves were used to identify the best signatures. Finally, quantitative PCR was used to validate the candidate biomarkers for early gastric cancer in the test samples (35 cancer and 33 normal samples). Using the SAM algorithm, 14 differential miRNAs were selected as candidate biomarkers. Using the TSP algorithm, hsa-miR-196a and hsa-miR-148a were obtained as a signature to differentiate between the early GC and normal samples. A coincidental result was observed in the test samples. hsa-miR-196a was upregulated and hsa-miR-148a was downregulated in the early GC samples. hsa-miR-196a and hsa-miR-148a have the potential to serve as candidate biomarkers for early GC.

Highly accurate two-gene signature for gastric cancer.

Large amount of expression data were generated by high-throughput experimental techniques such as microarray. Single algorithm cannot be widely accepted as suitable method for mining of gene expression data. Therefore, integration of different algorithms and extraction of more useful information from the expression data are the key problems for identification of biomarkers. Here, we used three machine learning algorithms to select feature genes based on gene profiling data of gastric cancer (GC). Then, a common divisor was extracted as candidate feature genes aggregation for Tree Building and Tree Pruning analysis by Decision Tree (DT) algorithm. Real-time quantitative PCR and immunohistochemistry (IHC) staining were used to validate the relative expression levels of the candidate feature genes. Receiver operating characteristic curves were used to analyse the classification sensitivity and specificity of the feature genes. A total of 174, 202, 149 feature genes were selected by Class Information Index, Information Gain Index and Relief algorithms, with a common divisor consisting of 32 genes. Using a DT algorithm to contribute to the classification rule sets, we identified COL2A1 and ATP4B as candidate biomarkers of GC. The expression levels of these two genes were validated by real-time PCR and IHC with high sensitivity (>90 %) and specificity (>90 %) in both training and test samples. We first introduced an integral and systematic data-mining model for identification of biomarkers based on gene expression data. The two-gene signature obtained by our predictive model could be used for recognizing the biological characteristic of GC.

Identification of recurrence-related genes by integrating microRNA and gene expression profiling of gastric cancer.

We previously analyzed the microRNA (miRNA) expression pattern in gastric cancer with and without recurrence and obtained 17 differentially expressed miRNAs with potential to predict recurrence risk for GC patients. In the present study, we aimed to investigate recurrence-related genes which may be regulated by the differentially expressed miRNAs identified in our prior research. Three different miRNA target gene databases (miRanda, TargetScan and PicTar) were used for searching the potential genes regulated by miRNAs. A combination was performed between miRNA target genes and recurrence-related gene expression profiling. Three bioinformatics algorithms (PAM, SVM and RF) were used to feature recurrence-related gene selection. In addition, we validated the expression levels of the genes in GC patients using real-time PCR. A total of 3,263 genes were identified as potential targets of 17 miRNAs. We identified 2,736 differential expressed genes using the SAM method based on 22K oligo microarray data which included 7 recurrence and 4 without recurrence GC samples. Combining the target genes regulated by miRNAs and the differentially expressed genes between recurrence and non-recurrence groups, we identified 228 differential genes for further study. Finally, we identified HNRPA0 and PRDM4 as risk biomarkers of GC patients, which were regulated by hsa-miR­194 and hsa-miR-373, respectively. Our data indicated that HNRPA0 and PRDM4 may be involved in the recurrence process of GC and have potential to act as new prognostic biomarkers in predicting recurrence risk for gastric cancer patients.

Notch1 activation contributes to tumor cell growth and proliferation in human hepatocellular carcinoma HepG2 and SMMC7721 cells.

Notch signaling controls cellular differentiation and proliferation. Recent studies have shown that Notch signaling plays an important role in the carcinogenesis and progression of a growing number of malignant tumors. We investigated the effect of Notch1 activation on human hepatocellular carcinoma (HCC). In five human HCC cell lines, it was found that SMMC7721 had relatively high while HepG2 relatively low expression of Notch1 and the activity of Notch signaling. Notch1 activation by transfection of active intracellular region of Notch1 (ICN1) into HCC HepG2 cells enhanced cell growth and proliferation, including in vitro single cell colony formation, anchorage-independent proliferation, and in vivo tumorigenicity. Notch1 activation also promoted HepG2 cell cycle progression. Suppression of Notch1 activation by RNAi of Notch1 or by γ-secretase inhibitor (GSI) in HCC SMMC7721 cells decreased cell growth capability and blocked cell cycle progression. Moreover, it was found that suppression of Notch1 activation induced SMMC7721 cell apoptosis, as demonstrated by apoptosis assays. These findings indicate that Notch1 activation promotes human HCC cell growth and proliferation, which may contribute to the progression of this type of malignant carcinoma.

Identification of candidate colon cancer biomarkers by applying a random forest approach on microarray data.

Colon cancer is the third most common cancer and one of the leading causes of cancer-related death in the world. Therefore, identification of biomarkers with potential in recognizing the biological characteristics is a key problem for early diagnosis of colon cancer patients. In this study, we used a random forest approach to discover biomarkers based on a set of oligonucleotide microarray data of colon cancer. Real-time PCR was used to validate the related expression levels of biomarkers selected by our approach. Furthermore, ROC curves were used to analyze the sensitivity and specificity of each biomarker in both training and test sample sets. Finally, we analyzed the clinical significance of each biomarker based on their differential expression. A single classifier consisting of 4 genes (IL8, WDR77, MYL9 and VIP) was selected by random forests with an average sensitivity and specificity of 83.75 and 76.15%. The differential expression levels of each biomarker was validated by real-time PCR in 48 test colon cancer samples compared to the matched normal tissues. Patients with high expression of IL8 and WDR77, and low expression of MYL9 and VIP had a significantly reduced median survival rate compared to colon cancer patients. The results indicate that our approach can be employed for biomarker identification based on microarray data. These 4 genes identified by our approach have the potential to act as clinical biomarkers for the early diagnosis of colon cancer.

Identification of hsa-miR-335 as a prognostic signature in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignancy and primary cause of death in Chinese cancer patients. Recurrence is a major factor leading to treatment failure and low level of 5-year survival rate in GC patients following surgical resection. Therefore, identification of biomarkers with potential in predicting recurrence risk is the key problem of the prognosis in GC patients. PATIENTS AND METHODS: A total of 74 GC patients were selected for systematic analysis, consisting of 31 patients with recurrence and 43 patients without recurrence. Firstly, miRNAs microarray and bioinformatics methods were used to characterize differential expressed miRNAs from primary tumor samples. Following, we used a ROC method to select signature with best sensitivity and specificity. Finally, we validated the signature in GC samples (frozen fresh and blood samples) using quantitative PCR. RESULTS: We have identified 12 differential miRNAs including 7 up-regulated and 5 down-regulated miRNAs in recurrence group. Using ROC method, we further ascertained hsa-miR-335 as a signature to recognize recurrence and non-recurrence cases in the training samples. Moreover, we validated this signature using quantitative PCR method in 64 test samples with consistent result with training set. A high frequency recurrence and poor survival were observed in GC cases with high level of hsa-miR-335 (P<0.001). In addition, we evaluated that hsa-miR-335 were involved in regulating target genes in several oncogenic signal-pathways, such as p53, MAPK, TGF-ß, Wnt, ERbB, mTOR, Toll-like receptor and focal adhesion. CONCLUSION: Our results indicate that the hsa-miR-335 has the potential to recognize the recurrence risk and relate to the prognosis of GC patients.

Construction and expression of a eukaryotic expression vector containing a fusion gene of the Hantaan virus S gene and hsp70 gene.

Hantavirus (HV) infection leads to a kind of severe systematic syndrome, hemorrhagic fever with renal syndrome (HFRS). Heat shock proteins (HSPs) can be used as adjuvants assisting soluble antigens to produce specific targets which can be attacked by cytotoxic T lymphocytes. For further research on HFRS vaccine, this study aimed to express Hantaan virus nucleocapsid protein (HTNV NP)-HSP70 fusion protein in COS-7 cells. First, an HTNV S gene encoding NP was amplified by PCR with a mutated termination code and cloned into eukaryotic expression vector pCDNA3.1(+), into which the full-length hsp70 gene had already been inserted, to form the S-hsp70 fusion expression vector pCDNA3.1(+)/S-hsp70. Then this recombinant plasmid was transfected into COS-7 cells by liposome, and eukaryotic expression of NP-HSP70 fusion protein was detected by immunocytochemistry and western blot. The results show that the eukaryotic expression vector pCDNA3.1(+)/S-hsp70 was successfully constructed and the NP-HSP70 fusion protein was effectively expressed in COS-7 cells. This study demonstrates that the NP-HSP70 fusion protein was expressed effectively from the pCDNA3.1(+)/S-hsp70 vector in a eukaryotic system and thus provides a basis for using this plasmid as a new DNA vaccine against HV infection.