Application of point-of-care ultrasound in patients receiving enteral nutrition.

OBJECTIVE: Enteral nutrition (EN) is the first-choice nutritional support, as it is more in line with normal physiological processes. During EN, the major goals to achieve include accurate confirmation of the feeding tube position, monitoring the gastric residual volume, assessing gastrointestinal motility, and monitoring the nutritional status of patients. With rapid development in technology, point-of-care ultrasound (POCUS) has become a more convenient and effective technical tool for monitoring critically ill patients receiving EN. In this review, we have summarized and discussed the value of POCUS in the implementation, monitoring, and evaluation of EN therapy to provide a reference for nutritional support of critically ill patients in critical care settings. MATERIALS AND METHODS: This is a narrative review. A literature search for Scopus-indexed articles was performed randomly using PubMed and MEDLINE databases as the primary sources. No specific term was used for the search. RESULTS: POCUS can be used for positioning of nasogastric and nasointestinal tubes, evaluation of gastric residuals and gastrointestinal motility as well as monitoring of nutritional status. CONCLUSIONS: POCUS is a real-time, highly repeatable, radiation-free, and non-invasive visual inspection technique, with high application value in assessing the nutritional status of patients receiving EN and guiding the development of further nutritional treatment plans. It is an important diagnostic and monitoring tool that can be used by the clinicians in the ICU.

Circ-ABCB10 acts as an oncogene in glioma cells via regulation of the miR-620/FABP5 axis.

OBJECTIVE: This study aims to investigate the biological function of circular RNA ABCB10 (circ-ABCB10) in regulating the progression of glioma and to study the possible underlying mechanisms. PATIENTS AND METHODS: The expression levels of circ-ABCB10, miR-620 and FABP5 mRNA in glioma tissues, normal surrounding tissues and glioma cell lines were measured by Real-time PCR (RT-PCR). Circ-ABCB10 was silenced by siRNA in glioma cell lines (U87, T98G). The proliferation, migration and invasion of glioma cells were measured by MTT, wound healing and transwell assays, respectively. The relationship between circ-ABCB10, miR-620 and FABP5 was tested by Dual-Luciferase assay. The expression of proteins was measured by Western blot. The cell cycle distribution and apoptosis were measured by flow cytometry. RESULTS: The expression levels of circ-ABCB10 and FABP5 in glioma tissues and cells were significantly higher than those in their normal counterparts. Moreover, the expression of miR-620 was lower in glioma tissues. Silencing of circ-ABCB10 in glioma cells significantly inhibited the proliferation, migration and invasion of glioma cells. Moreover, downregulation of circ-ABCB10 induced cell cycle arrest and apoptosis in glioma cells. Furthermore, inhibition of miR-620 showed the opposite effects to silencing circ-ABCB10 on glioma cells. Dual-Luciferase reporter assays demonstrated that circ-ABCB10 could bind to miR-620 and that FABP5 was a direct target of miR-620. Western blot results showed that circ-ABCB10 could stabilize the expression of FABP5, while miR-620 decreased the expression of FABP5. Furthermore, overexpression of FABP5 abrogated the silencing effects of circ-ABCB10 in glioma cells. CONCLUSIONS: These data suggest that circ-ABCB10 affects glioma progression by regulating the miR-620/FABP5 axis, and circ-ABCB10 might be used as a potential target for the treatment of glioma.

SGK2 promotes renal cancer progression via enhancing ERK 1/2 and AKT phosphorylation.

OBJECTIVE: Increasing studies reported that the serum- and glucocorticoid-inducible kinases (SGKs) contributed to the tumorigenesis of various cancer. In this article, we are aiming to explore the function of SGK2 in renal cell cancer (RCC). PATIENTS AND METHODS: In this study, the SGK2 expression was quantified by Western blot (WB) in multiple RCC cell lines. And in vitro SGK2 knockdown and overexpression experiments were also performed. In addition, molecular function analysis was performed using FunRich software V3. The Cancer Genome Atlas (TCGA) database was retrieved to verify the association between the SGK2 expression and the prognosis of RCC patients. RESULTS: We found that SGK2 was up-regulated in RCC tissues compared with adjacent normal tissues, and the SGK2 expression also increased in various RCC cell lines compared to that in the normal epithelial cell line HK-2. Meanwhile, the SGK2 expression was significantly associated with the survival rate of RCC patients. Functional experiments showed that silencing SGK2 expression inhibited RCC cells proliferation, migration, colony formation and invasion abilities in vitro, whereas opposite results were uncovered after overexpressing SGK2 in RCC cells. Furthermore, functional analyses showed that SGK2 related genes were associated with protein serine/threonine kinase activity, guanosine triphosphatase (GTPase) activity, guanyl-nucleotide exchange factor activity, and motor activity. Protein interaction analysis identified that growth factor receptor-bound protein 2 (GRB2), one of the most important upstream components in the growth factor signaling pathway, was significantly enriched in SGK2 related genes. In addition, the WB assay validated that SGK2 could promote the phosphorylation of ERK 1/2 and AKT. CONCLUSIONS: Our results suggested that SGK2 promoted RCC progression by mediating the phosphorylation of extracellular regulated protein kinases (ERK) 1/2 and Protein kinase B (AKT/PKB), indicating that SGK2 might serve as a potential prognostic marker and therapeutic target for renal cancer patients.

Comprehensive review and annotation of susceptibility SNPs associated with obesity-related traits.

We aimed to summarize the results of genetic association studies for obesity and provide a comprehensive annotation of all susceptibility single nucleotide polymorphisms (SNPs). A total of 72 studies were summarized, resulting in 90,361 susceptibility SNPs (738 index SNPs and 89,623 linkage disequilibrium SNPs). Over 90% of the susceptibility SNPs are located in non-coding regions, and it is challenging to understand their functional significance. Therefore, we annotated these SNPs by using various functional databases. We identified 24,623 functional SNPs, including 4 nonsense SNPs, 479 missense SNPs, 399 untranslated region SNPs which might affect microRNA binding, 262 promoter and 5,492 enhancer SNPs which might affect transcription factor binding, 7 splicing sites, 76 SNPs which might affect gene methylation levels, 1,839 SNPs under natural selection and 17,351 SNPs which might modify histone binding. Expression quantitative trait loci analyses for functional SNPs identified 98 target genes, including 69 protein coding genes, 27 long non-coding RNAs and 3 processed transcripts. The percentage of protein coding genes that could be correlated with obesity-related pathways directly or through gene-gene interaction is 75.36 (52/69). Our results may serve as an encyclopaedia of obesity susceptibility SNPs and offer guide for functional experiments.

Inflammatory factor in donor liver and its effect on recipient myocardial injury after liver transplantation.

OBJECTIVE: To study the inflammatory factors in donor livers and its effect on recipient myocardial injury after liver transplantation recipients. PATIENTS AND METHODS: Eighteen patients who underwent orthotopic liver transplantations between January 2014 and December 2015 in our hospital were selected. A portion of the hepatic venous blood of donor's livers was preserved in heparinized tubes after partial resection. The concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and the activity of lactate dehydrogenase (LDH) in serum were measured. The concentrations of TNF-α, IL-6, cTnI, and CK-MB, and the activity of LDH in serum from the central venous blood of recipients were measured at several time points. RESULTS: Persistent myocardial injuries were found in five patients, six experienced a transient increase of cardiac markers after surgery and returned to normal levels 24 h after surgery, and the others were normal. The comparison of the levels of inflammatory factors in serum between the five donors and recipients at different stages showed that the levels of myocardial markers of the donor livers which were supplied to the five cardiac injured patients were all significantly higher than those of other donor's livers, while the levels of serum inflammatory factors in recipients showed no changes during the T0-T2 stage but increased significantly during T3-T5 (p < 0.05). The cardiac function after surgery was significantly different from that before surgery and that of the recipients without myocardial injury (p < 0.05). CONCLUSIONS: Blood pressure changes before surgery may affect the levels of inflammatory factors in donor's liver and cause postoperative myocardial injury in recipients. Proper hypotensive therapy for donors before partial liver resection can prevent postoperative myocardial injury in recipients.

Polymorphisms of TGFB1, TLE4 and MUC22 are associated with childhood asthma in Chinese population

Objective: To investigate whether the genetic variants of TGFB1, TLE4, MUC22 and IKZF3 are associated with the development of asthma in Chinese children. Methods: 572 adolescent asthma patients and 590 age-matched healthy controls were included in this study. A total of four SNPs were genotyped, including rs2241715 of TGFB1, rs2378383 of TLE4, rs2523924 of MUC22, and rs907092 of IKZF3. Allele frequencies of the patients and the control group were compared by the Chi-square test. The Student t test was used to analyse the relationship between genotypes and clinical feature of the patients. Results: Patients were found to have significantly different frequencies of allele A of rs2241715, allele G of rs2378383 and allele A of rs2523924 as compared with the controls (40.4% vs. 45.9%, p = 0.01 for rs2241715; 17.2% vs. 13.4%, p=0.01 for rs2378383; 15.3% vs. 11.9%, p = 0.02 for rs2523924). For patients with severe asthma, those with genotype AA/AG of rs2241715 had remarkably higher FEV1% as compared with those with genotype GG (59.1 ± 4.3% vs. 55.4 ± 3.7%, p < 0.001). Moreover, those with genotype GG/GA of rs2378383 had remarkably lower FEV1% as compared with those with genotype AA (54.6 seg ± 2.9% vs. 58.6 ± 4.1%, p < 0.001). Conclusions: Genes TGFB1, TLE4 and MUC22 are associated with the risk of childhood asthma in Chinese population. Our results associating TGFB1 and TLE4 with clinical features of asthma suggest potential application of these parameters in the management of asthma children (AU)

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Ontogeny of human IgE-expressing B cells and plasma cells.

BACKGROUND: IgE-expressing (IgE+ ) plasma cells (PCs) provide a continuous source of allergen-specific IgE that is central to allergic responses. The extreme sparsity of IgE+ cells in vivo has confined their study almost entirely to mouse models. OBJECTIVE: To characterize the development pathway of human IgE+ PCs and to determine the ontogeny of human IgE+ PCs. METHODS: To generate human IgE+ cells, we cultured tonsil B cells with IL-4 and anti-CD40. Using FACS and RT-PCR, we examined the phenotype of generated IgE+ cells, the capacity of tonsil B-cell subsets to generate IgE+ PCs and the class switching pathways involved. RESULTS: We have identified three phenotypic stages of IgE+ PC development pathway, namely (i) IgE+ germinal centre (GC)-like B cells, (ii) IgE+ PC-like 'plasmablasts' and (iii) IgE+ PCs. The same phenotypic stages were also observed for IgG1+ cells. Total tonsil B cells give rise to IgE+ PCs by direct and sequential switching, whereas the isolated GC B-cell fraction, the main source of IgE+ PCs, generates IgE+ PCs by sequential switching. PC differentiation of IgE+ cells is accompanied by the down-regulation of surface expression of the short form of membrane IgE (mIgES ), which is homologous to mouse mIgE, and the up-regulation of the long form of mIgE (mIgEL ), which is associated with an enhanced B-cell survival and expressed in humans, but not in mice. CONCLUSION: Generation of IgE+ PCs from tonsil GC B cells occurs mainly via sequential switching from IgG. The mIgEL /mIgES ratio may be implicated in survival of IgE+ B cells during PC differentiation and allergic disease.

Resveratrol attenuates senescence of adipose-derived mesenchymal stem cells and restores their paracrine effects on promoting insulin secretion of INS-1 cells through Pim-1.

OBJECTIVE: The paracrine effects of mesenchymal stem cells (MSCs) were weakened during aging. This study explored whether resveratrol can attenuate senescence of adipose-derived MSCs (ADMSCs) and whether Pim-1 is involved in resveratrol's effect on paracrine of ADMSCs and insulin secretion of INS-1 cells. MATERIALS AND METHODS: CCK-8 assay and SA-b-gal assay were performed to test the protective effect of resveratrol on senescent models. QRT-PCR and western blot analysis were performed to analyze of senescence- and ß-cell associated genes. QRT-PCR and ELISA analysis was performed to test telomere length and activity. Immunofluorescence and ELISA assay were performed to assess the paracrine effects on promoting insulin secretion of INS-1 cells. RESULTS: Resveratrol could protect ADMSCs from H2O2 and D-glucose-induced senescence and also attenuate senescence in long-term cultured ADMSCs in vitro. In addition, resveratrol attenuated H2O2 induced higher expression of senescence-associated genes, including P53, P21, Cyclin D1, IL-6 and MMP1, but increased the expression of Sirt1, a well-known anti-senescence gene. Resveratrol significantly enhanced Pim-1 expression in aging ADMSCs through PI3K/AKT signal pathway. The conditioned medium (CM) of ADMSCs enhanced insulin secretion and expression of the key genes for ß-cell function including TFAM, PDX1, GLUT2 and HNF-1α via Pim-1. INS-1 cells with Pim-1 knockdown had decreased insulin secretion. CONCLUSIONS: This study firstly reported that resveratrol has a protective effect on senescence of ADMSCs and can preserve the paracrine effect of the ADMSCs on promoting insulin secretion of INS-1 cells via Pim-1. Therefore, it might be a promising adjuvant agent for future MSCs based therapy.

A review on steroidal 5α-reductase inhibitors for treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a kind of common noncancerous prostate gland enlargement with growing tendency in recent years. 5α-reductase is the key enzyme responsible for dihydrotestosterone biosynthesis and has been considered as an important target for designing inhibitors as potent therapeutic agents for BPH. Finasteride, the first steroidal 5α-reductase inhibitor, has been marketed worldwide as a drug for BPH. During these years, many other novel types of 5α-reductase inhibitors are being studied. This review summarizes recent advancement in steroidal 5α-reductase inhibitors.

Combined application of blocking antibodies and MicroRNA interference in inhibiting CD44 expression.

BACKGROUND: We sought to explore the effect of CD44 targeting on the tolerance to memory cell-mediated graft rejection. METHODS: We developed a cardiac transplantation model in nude mice and administered anti-CD44 monoclonal antibodies (mAbs) to these mice. Then, we used anti-CD44 mAb and CD44-interfering microRNA (miRNA) to inhibit CD44 expression in vitro. RESULTS: The median survival time (MST) associated with multiple intraperitoneal injections was >100 days, whereas that associated with CD4(+) Tm cells blocked CD44 and that associated with a single intraperitoneal injection of anti-CD44 mAb was 11 and 10.3 days, control group was 5.5 days. The inhibition effect of the anti-CD44 mAb in 3T3 cells significantly reduced with cell proliferation. Used CD44 miRNA in 3T3 cells, the most obvious inhibition effect of mRNA appeared at 48 hours after transfection and the inhibition decreased subsequently. In combination, antibody-mediated blocking and miRNA showed some synergistic effects. CONCLUSION: The inhibition of CD44 can significantly prolong the MST in memory models. The inhibition effect of combined application showed limitations with regard to cell proliferation and duration of action, but the short-term synergistic effect of the combined approach was stronger than the effects of individual approaches.

Association between a common mitochondrial DNA D-loop polycytosine variant and alteration of mitochondrial copy number in human peripheral blood cells.

BACKGROUND: A T-to-C transition at mitochondrial DNA (mtDNA) nucleotide position 16189 can generate a variable length polycytosine tract (poly-C). This tract variance has been associated with disease. A suggested pathogenesis is that it interferes with the replication process of mtDNA, which in turn decreases the mtDNA copy number and generates disease. METHODS: In this study, 837 healthy adults' blood samples were collected and determined for their mtDNA D-loop sequence. The mtDNA copy number in the leucocytes and serum levels of oxidative thiobarbituric acid reactive substance (TBARS) and antioxidative thiols were measured. All subjects were then categorised into three groups: wild type or variant mtDNA with presence of an interrupted/uninterrupted poly-C at 16180-16195 segment. RESULTS: A step-wise multiple linear regression analysis identified factors affecting expression of mtDNA copy number including TBARS, thiols, age, body mass index and the mtDNA poly-C variant. Subjects harbouring a variant uninterrupted poly-C showed lowest mean (SD) mtDNA copy number (330 (178)), whereas an increased copy number was noted in subjects harbouring variant, interrupted poly-C (420 (273)) in comparison with wild type (358 (215)). The difference between the three groups and between the uninterrupted poly-C and the composite data from the interrupted poly-C and wild type remained consistent after adjustment for TBARS, thiols, age and body mass index (p=0.001 and p=0.011, respectively). A trend for decreased mtDNA copy number in association with increased number of continuous cytosine within the 16180-16195 segment was noted (p(trend)<0.006). CONCLUSIONS: Our results substantiate a previous suggestion that the mtDNA 16189 variant can cause alteration of mtDNA copy number in human blood cells.

Detecting a deletion in the coding region of the bovine bone morphogenetic protein 15 gene (BMP15).

The aim of this study was to detect polymorphism in the bovine bone morphogenetic protein 15 (BMP15) gene. On the basis of PCR-SSCP and DNA sequencing, a 4-bp deletion was identified in the coding region of the gene. Sequence analysis revealed that the deletion altered the reading frame and introduced a stop codon at position 264. Eight breeds (Luxi, Qinchuan, Nanyang, Jinnan, Bohai Black, Menggolian, Holstein, and Simmental) were genotyped by PCR-SSCP. No cows homozygous for this mutation were observed in these breeds. Heterozygous cows were detected in Luxi, Qinchuan, Nanyang, Jinnan and Bohai Black cattle. Fecundity was not increased in heterozygous individuals.

"Full house" proliferative glomerulonephritis: an unreported presentation of subacute infective endocarditis.

A severely ill 65-year-old man presented with symptoms of shortness of breath, edema and vasculitidic purpura over his lower extremities. He had severe mitral regurgitation which had not been surgically treated. Hematologic examination demonstrated leukocytosis with profound anemia. Other blood tests revealed impaired renal function, hypoalbuminemia, hypocomplementemia and mixed-type cryoglobulinemia. Urinalysis showed proteinuria, hematuria and pyuria, typical of a nephritic sediment. Renal biopsy indicated diffuse proliferative glomerulonephritis and a "full house" deposition in immunofluorescence study (positive for C3, C4, C1q, IgG, IgA and IgM), resembling the pathologic findings in class IV lupus nephritis. Although subacute bacterial endocarditis was initially suspected owing to a history of a predisposing valvular heart disease, probable vegetation shown by cardiac sonography and a clinical picture suggestive of a chronic infection, it was thought unlikely due to the entire afebrile course and initial sterile blood cultures. However, the blood cultures repeated 2 weeks after admission grew 3 sets of viridans streptococci. Following a course of penicillin and gentamicin treatment, his renal function, anemia and abnormal urine sediments improved gradually. Diffuse proliferative glomerulonephritis is well known to occur in infective endocarditis. However, the "full house" immunostaining in immunofluorescence study has never been reported. This case adds a new entity to the differential diagnosis of "full house" immune complex-related glomerulonephritis and exemplifies the need to maintain a high index of suspicion for underlying infectious disorders when facing glomerulonephritic or vasculitic syndrome.

Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus.

Diabetes is associated with renal calcium and magnesium wasting, but the molecular mechanisms of these defects are unknown. We measured renal calcium and magnesium handling and investigated the effects of diabetes on calcium and magnesium transporters in the thick ascending limb and distal convoluted tubule in streptozotocin (STZ)-induced diabetic rats. Rats were killed 2 weeks after inducing diabetes, gene expression of calcium and magnesium transporters in the kidney was determined by real-time polymerase chain reaction, and the abundance of protein was assessed by immunoblotting. Our results showed that diabetic rats had significant increase in the fractional excretion for calcium and magnesium (both P < 0.01), but not for sodium. Reverse transcriptase-polymerase chain reaction revealed significant increases in messenger RNA abundance of transient potential receptor (TRP) V5 (223 +/- 10%), TRPV6 (177 +/- 9%), calbindin-D28k (231 +/- 8%), and TRPM6 (165 +/- 8%) in diabetic rats. Sodium chloride cotransporter was also increased (207 +/- 10%). No change was found in paracellin-1 (cortex: 108 +/- 8%; medulla: 110 +/- 10%). Immunofluorescent studies of renal sections showed significant increase in calbindin-D28k (238 +/- 10%) and TRPV5 (211 +/- 10%), but no changes in paracellin-1 in Western blotting (cortex: 110 +/- 7%; medulla: 99 +/- 7%). Insulin administration completely corrected the hyperglycemia-associated hypercalciuria and hypermagnesiuria, and reversed the increase of calcium and magnesium transporter abundance. In conclusion, our results demonstrated increased renal calcium and magnesium transporter abundance in STZ-induced diabetic rats, which may represent a compensatory adaptation for the increased load of calcium and magnesium to the distal tubule.

Guillain-Barré syndrome in southern Taiwan: clinical features, prognostic factors and therapeutic outcomes.

To determine the clinical features, prognostic factors, and therapeutic results of Guillain-Barré syndrome (GBS) in order to improve the therapeutic strategy for this disease. We retrospectively reviewed the electrodiagnostic study and medical records of patients with GBS admitted to Chang Gung Memorial Hospital, Kaohsiung, between January 1986 and December 2000. Outcomes and prognosis were followed-up after 1 year. Ninety-six patients were enrolled in this study. According to the clinical and electrophysiological findings, 77 patients were acute inflammatory demyelinating polyradiculoneuropathy, seven were Miller Fisher syndrome, and six were axonal forms, and six were unclassified. At a follow-up of 1 year, 61 patients (64%) recovered, 30 (31%) had residua and five (5%) died. Amongst these 30 had residua, including unassisted gait in 19, assisted gait in four, and wheel/bed bound in seven. According to the statistical analysis, disabilities at the nadir (P < 0.0001) and at admission (P = 0.014) were significant prognostic factors. Variables used for the stepwise logistic regression, and the results revealed that after analysis for all the above variables, only disability at the nadir (P < 0.0001) was independently associated with the treatment failure rate. Our study revealed 27% of cases in need of respiratory support during hospitalization, and 5% of hospital-treated patients die from the complications. Furthermore, 31% had residua at a follow-up of 1 year or more. If prognostic factors are considered, disability at the nadir during hospitalization demonstrates consistently poor therapeutic outcomes. Therefore, early diagnosis, choice of appropriate treatment, and preventing complications during acute stages are essential to maximize the potential for survival.