Evaluation of postoperative feeding strategies in children with intestinal atresia: A single-center retrospective study.

Objectives: Postoperative enteral nutrition has a significant influence on the prognosis of patients with congenital intestinal atresia. Currently, there is no precise guidance on enteral nutrition management. This study aimed to compare the outcomes of different feeding strategies based on the initial volume and daily advancement in postoperative patients with congenital intestinal atresia. Methods: This study was a retrospective study collected from October 2019 to July 2021 in Shenzhen Children's Hospital. According to the initial volume and daily advancement, the patients were divided into high-dose group and low-dose group. General basic information such as age, sex, and lesion type was gathered. The postoperative outcome included the levels of hemoglobin (HGB), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DB), length of stay, length of total PN, time to reach 100% enteral nutrition (EN) (120 kcal·kg-1·d-1), infection incidence and intestinal failure associated liver disease (IFALD) incidence (DB>2 mg·dL-1). Results: In total, 32 patients with congenital intestinal atresia were identified. There was no significant difference between the high-dose group and the low-dose group in the baseline characteristic. The length of time to reach 100% (p = 0.001) enteral nutrition and postoperative hospital stay (p = 0.092) were shorter in the high-dose group. In the high-dose group, patients at discharge were with not only lower levels of DB (p = 0.009), AST (p = 0.109) and ALT (p = 0.045) but also higher level of ALB (p = 0.459) and hemoglobin (p = 0.354). The incidence of IFALD was significantly lower in the high-dose group (p = 0.032). There was no significant difference in the overall incidence of postoperative complications. Conclusions: Within the limitations, the findings of this study suggest that High-dose feeding (initial volume>15 ml·kg-1·d-1, daily advancement>10 ml·kg-1·d-1) is beneficial for the prognosis of patients diagnosed with congenital intestinal atresia treated by intestinal.

A 16-miRNA Prognostic Model to Predict Overall Survival in Neuroblastoma.

Neuroblastoma is the most malignant childhood tumor. The outcome of neuroblastoma is hard to predict due to the limitation of prognostic markers. In our study, we constructed a 16-miRNA prognostic model to predict the overall survival of neuroblastoma patients for early diagnosis. A total of 205 DE miRNAs were screened using RNA sequencing data from GSE121513. Lasso Cox regression analysis generated a 16-miRNA signature consisting of hsa-let-7c, hsa-miR-135a, hsa-miR-137, hsa-miR-146a, hsa-miR-149, hsa-miR-15a, hsa-miR-195, hsa-miR-197, hsa-miR-200c, hsa-miR-204, hsa-miR-302a, hsa-miR-331, hsa-miR-345, hsa-miR-383, hsa-miR-93, and hsa-miR-9star. The concordance index of multivariate Cox regression analysis was 0.9, and the area under the curve (AUC) values of 3-year and 5-year survival were 0.92 and 0.943, respectively. The mechanism was further investigated using the TCGA and GSE90689 datasets. Two miRNA-gene interaction networks were constructed among DEGs from two datasets. Functional analysis revealed that immune-related processes were involved in the initiation and metastasis of neuroblastoma. CIBERSORT and survival analysis suggested that lower CD8 T-cell proportion and higher SPTA1 expressions were related to a better prognosis. Our study demonstrated that the miRNA signature may be useful in prognosis prediction and management improvement.

Telbivudine plus adefovir therapy for chronic hepatitis B patients with virological breakthrough or genotypic resistance to telbivudine.

BACKGROUND/AIM: There is very limited experience in the management of telbivudine (LdT)-associated virological breakthrough (VBT) and resistance in the treatment of chronic hepatitis B (CHB) patients, and the guideline recommendations are primitively based on the general principles of rescue therapy to nucleos(t)ide analog resistance. The aim of this study is to determine the effect of the addition of adefovir (ADV) in hepatitis B e antigen (HBeAg)-positive CHB patients with VBT or resistance to LdT. METHODS: Thirty-seven CHB patients with confirmed VBT and 31 patients with genotypic resistance to LdT were enrolled and thereafter treated with a combination of LdT and ADV for 12 months. RESULTS: Combination therapy was safe and the majority of patients tolerated the therapy. LdT+ADV led to rapid decreases in viral loads, and viral replications were persistently suppressed, with 2.17 (VBT) and 2.31 (resistance) log(10) copies/ml reductions 12 months after rescue therapy, respectively. The rates corresponding to virological and biochemical responses were similar between the two groups at the end of observations (70.3 vs. 74.2% for virological response, P=0.720; 64.0 vs. 65.5% for biochemical response, P=0.907). The cumulative rates of serological responses were higher in patients with VBT than in those with resistance (35.1 vs. 9.67% for HBeAg loss, P=0.014; 10.8 vs. 3.23% for HBeAg/anti-HBe seroconversion, P=0.233). CONCLUSION: LdT and ADV combination therapy led to significant decreases in serum hepatitis B virus DNA levels and normalization of alanine aminotransferase levels in patients with VBT or genotypic resistance to LdT. This rescue strategy was also associated with a higher rate of HBeAg serological outcomes in patients with confirmed LdT-related VBT.

Validation of the iHealth BP3 upper-arm blood pressure monitor, for clinic use and self-measurement, according to the European Society of Hypertension International Protocol revision 2010.

OBJECTIVE: This study aimed to evaluate the performance of the iHealth BP3 upper-arm blood pressure monitor, which is designed for clinic use and self-measurement of blood pressure using Apple touch devices as an interface. METHODS: The European Society of Hypertension International Protocol (ESH-IP) revision 2010 for the validation of blood pressure measuring devices in adults was followed precisely. Ninty-nine couples of test device and reference blood pressure measurements were obtained during the study (three pairs for each of the 33 participants). RESULTS: The 33 participants, age 47.1±12.3 years (age range 27-69 years) and arm circumference 30.0±4.4 cm, had a mean systolic blood pressure (SBP) of 143.9±27.4 mmHg and a mean diastolic blood pressure (DBP) of 90.1±18.3 mmHg. The device passed all of the requirements fulfilling the standards of the protocol, and the mean±SD device-observer difference was 2.8±4.2 mmHg for SBP and -0.4±3.5 mmHg for DBP. CONCLUSION: According to the results of the validation study on the basis of the ESH-IP revision 2010, the iHealth BP3 can be recommended for clinic use and self-measurement in an adult population.

Involvement of reactive oxygen species and JNK in increased expression of MCP-1 and infiltration of inflammatory cells in pressure-overloaded rat hearts.

Increasing evidence has shown that inflammation is involved in pressure overload-induced cardiac remodeling. Monocyte chemoattractant protein-1 (MCP-1) plays a pivotal role in the inflammatory process. However, the mechanisms underlying the upregulation of MCP-1 expression remain poorly understood. In the present study, we examined the hypothesis that an increased production of reactive oxygen species (ROS) mediates the upregulation of MCP-1. In a pressure-overloaded rat heart model with abdominal aortic coarctation (AC), superoxide dismutase-inhibitable cytochrome C reduction assay showed that ROS generation in the myocardium increased significantly at 1 week by 61% (n=8, P<0.01), peaked at 2 weeks and maintained these high levels for 4 weeks. The elevation of ROS was paralleled by the increased expression of MCP-1 and left ventricular remodeling (cardiac hypertrophy, perivascular and interstitial fibrosis). The oral administration of the antioxidant, N-acetylcysteine (NAC, 0.2 g/kg/day), for 2 or 4 weeks, significantly attenuated ROS production by 69 and 68%, respectively (n=8, P<0.01), as well as left ventricular remodeling. NAC treatment for 2 weeks also significantly reduced the MCP-1 mRNA and protein levels by 52 and 60%, respectively (n=4-8, both P<0.01), but had no effect on blood pressure. In the rats with AC at 2 weeks, when MCP-1 expression and inflammation changes were overt, immunoblotting with phospho-specific antibodies revealed that extracellular regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK), but not p38 mitogen-activated protein kinase, were activated. NAC administration attenuated JNK activation, but had no effect on ERK. Our results suggest that increased ROS production may play an important role in the increased expression of MCP-1 in pressure overload-induced cardiac remodeling. JNK is likely involved in the signaling pathway.

Serum omentin-1 levels are inversely associated with the presence and severity of coronary artery disease in patients with metabolic syndrome.

CONTEXT: Omentin-1, an adipokine secreted from visceral adipose tissue, has been reported to be associated with coronary artery disease (CAD) and metabolic disorders. OBJECTIVE: To clarify the relationship between serum omentin-1 levels and the presence and severity of CAD in patients with metabolic syndrome (MetS). METHODS: We measured serum omentin-1 levels in 175 consecutive patients with MetS and in 46 controls. RESULTS: Serum omentin-1 levels are inversely associated with the presence and angiographic severity of CAD in MetS patients. CONCLUSIONS: Serum omentin-1 might be a potential biomarker to predict the development and progression of CAD in MetS patients.

[The relationship between reactive oxygen species-dependent activation of p38 MAPK and the expression of tumor necrosis factor-α in cultured cardiomyocytes].

AIM: To investigate the role of p38 mitogen-activated protein kinase(MAPK) in lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) expression in neonatal rat cardiomyocytes and to determine the relationship between reactive oxygen species (ROS) and p38 MAPK activation. METHODS: Cardiomyocytes were isolated from neonatal Sprague-Dawley rats and cultured by differential adhesion. Expression of TNF-α was determined in culture medium by ELISA. Activation of p38 MAPK was determined by Western blot analysis with phospho-specific antibody. ROS generation in cardiomyocytes was determined by peroxide specific probe 2', 7'-dichlorofluorescin diacetate (DCF-DA). RESULTS: In cardiomyocytes stimulated with LPS, the content of TNF-α in culture medium correlated with the activity of p38 MAPK in a time-dependent manner. The activation of p38 was observed after stimulation of 1 mg/L LPS for 1 h. TNF-α accumulated significantly in culture medium at 3 h after stimulation of LPS (P<0.05), which was remarkably attenuated by pretreatment with p38 MAPK specific inhibitor SB203580 (P<0.01). Furthermore, the production of ROS in cardiomyocytes stimulated with LPS was also increased at 1 h after stimulation of LPS, consistent with p38 MAPK activity. Pretreatment with antioxidants such as N-acetylcysteine and diphenyleneiodonium significantly inhibited the activation of p38 MAPK compared with LPS control (P<0.05). There was no significance in the activity of p38 MAPK among antioxidants pretreatment and non-LPS control groups. CONCLUSION: The activation of p38 MAPK plays an important role in TNF-α expression in LPS-stimulated cardiomyocytes and the increase of ROS production is prerequisite for the activation of p38 MAPK.

The osteoprotective effect of Radix Dipsaci extract in ovariectomized rats.

AIM: The objective of the present study was to systematically evaluate the effects of Radix Dipsaci extract (RDE) on postmenopausal osteoporosis. MATERIALS AND METHODS: OVX or sham operations were performed on sixty 3-month-old virgin Sprague-Dawley rats that were divided into six groups: sham control group (sham, n=10); OVX control group (OVX, n=10); 17beta-estradiol treatment group (E2, n=10); three Radix Dipsaci extract treatment groups RDE100 (n=10), RDE300 (n=10) and RDE500 (n=10). The treatment began 4 weeks after the surgery and lasted for 16 weeks. Bone mass, bone turnover and strength were analyzed by DEXA, biochemical markers and three-point bending test. The trabecular bone microarchitecture was evaluated by MicroCT. RESULTS: 16 weeks treatment of RDE slowed down the body weight gain and prevented the loss of bone mass induced by the OVX. The prevention effect on bone loss was due to altering the rate of bone remodeling, which could be inferred from the decreased level of bone turnover markers, such as serum ALP, OC and urinary DPD. The changes of urinary calcium and phosphorus excretion provided the same evidence. The treatment could also enhance the bone strength and prevent the deterioration of trabecular microarchitecture. CONCLUSIONS: Our study provides evidence that Radix Dipsaci extract will have potential to be used for treatment of postmenopausal osteoporosis.

Conjugation with alpha-linolenic acid improves cancer cell uptake and cytotoxicity of doxorubicin.

The synthetic DOX-LNA conjugate was characterized by proton nuclear magnetic resonance and mass spectrometry. In addition, the purity of the conjugate was analyzed by reverse-phase high-performance liquid chromatography. The cellular uptake, intracellular distribution, and cytotoxicity of DOX-LNA were assessed by flow cytometry, fluorescence microscopy, liquid chromatography/electrospray ionization tandem mass spectrometry, and the tetrazolium dye assay using the in vitro cell models. The DOX-LNA conjugate showed substantially higher tumor-specific cytotoxicity compared with DOX.

NO-donating genistein prodrug alleviates bone loss in ovariectomised rats.

QUESTIONS UNDER STUDY: To find a more potent alternative with less oestrogen-related side effects for hormone replacement therapy (HRT) in postmenopausal osteoporosis, we designed and synthesized a NO-releasing prodrug of genistein (NO-G) according to the structure of NONSAIDs. The purpose of this study was to evaluate the effects of the prodrug on bone in ovariectomised (OVX) rats. METHODS: Forty-eight adult Sprague-Dawley female rats were ovariectomised and treated with vehicle, 9 mg/kg genistein and 4.5, 9 or 18 mg/kg NO-G by oral administration daily. The bioassays were performed in terms of bone mineral density (BMD), mechanical testing, bone formation markers, bone alkaline phosphatase (b-ALP) and osteocalcin (OCN) and bone resorption marker urine deoxypyridinoline (DPD). In addition, the effects of the drugs on uterus and body weight were examined. RESULTS: After treatment for 12 weeks, the BMD of whole femur and tibia in the NO-G (9 and 18 mg/kg) groups were 12.1% and 12.2% higher than that of OVX group (P<0.01); the bending strength of the femur was 11.2% and 12.2% higher than OVX group (P<0.01). The OVX-induced increase of serum b-ALP, OCN and urinary DPD were markedly attenuated. The prodrug showed no side effects on uterus and body weight. CONCLUSIONS: The NO-releasing prodrug of genistein improves the bone loss in OVX rats without stimulatory effects on the uterus, which suggests that the product could potentially be used for the prevention and treatment of postmenopausal osteoporosis.

Nitric oxide-donating genistein prodrug: design, synthesis, and bioactivity on MC3T3-E1 cells.

To find a more potent alternative with less estrogen-related side effects for hormone replacement therapy, we designed and synthesized a nitric oxide (NO)-releasing prodrug of genistein, named NO-donating genistein (NO-G). The characteristics of NO-G were determined by melting point, NMR spectroscopy, and mass spectrometric analysis. HPLC has been used to test the new prodrug's stability. The releasing capacity of NO-G was tested by Griess reagent in vitro. The bioactivities of NO-G on proliferation, differentiation, and mineralization of the osteoblastic cell line MC3T3-E1 were determined by MTT assay, flow cytometric analysis, measurement of the alkaline phosphatase (ALP) activity and the secreted osteocalcin (OCN), and Alizarin Red-S staining. The product showed 1H NMR spectra and relative molecular mass in agreement with the designed structure, and it was stable in buffer solution. NO-G continually released low level NO within 5 h in MC3T3-E1 cells. NO-G caused a significant elevation of cell growth, ALP activity, and OCN secretion in both dose- and time-dependent manner. Furthermore, the Alizarin Red-S staining showed that NO-G promoted mineralization of MC3T3-E1 cells. These effects were all significantly greater than those of its parent drugs. The results suggested that NO-G might be a novel drug for the treatment of postmenopausal osteoporosis.

Simvastatin inhibits lipopolysaccharide-induced tumor necrosis factor-alpha expression in neonatal rat cardiomyocytes: The role of reactive oxygen species.

Tumor necrosis factor-alpha (TNF-alpha) is implicated in heart failure and cardiomyocytes themselves can express TNF-alpha. Nevertheless, the mechanisms and regulations of TNF-alpha expression in cardiomyocytes remain poorly understood. The present study was to investigate the effects of simvastatin on TNF-alpha expression in cardiomyocytes and the underlying molecular mechanisms. In neonatal rat cardiomyocytes, RT-PCR and ELISA showed lipopolysaccharide (LPS)-induced TNF-alpha expression was attenuated by simvastatin pretreatment in a dose-dependent manner. The reactive oxygen species (ROS) scavenger N-acetylcysteine and the NADPH oxidase inhibitor diphenyleneiodonium also inhibited the LPS-induced expression of TNF-alpha. Dichlorofluorescein-fluorescence and cytochrome c reduction assay indicated LPS increased ROS generation and NADPH oxidase activity in cardiomyocytes, which were abrogated by simvastatin. Furthermore, similar to LPS, exogenous hydrogen peroxide also increased TNF-alpha secretion, but simvastatin did not significantly affect the hydrogen peroxide-induced TNF-alpha secretion. All the effects of simvastatin as mentioned above were completely reversed by concomitant pretreatment with mevalonate, a key intermediate during cholesterol synthesis. These results suggest that simvastatin attenuates LPS-induced TNF-alpha expression in cardiomyocytes via inhibition of activation of NADPH oxidase and subsequent ROS generation.

Inhibitory effect of cyclosporin A on growth and collagen synthesis of rat cardiac fibroblasts induced by arginine vasopressin.

AIM: To investigate the effects of cyclosporin A (CsA) on growth and collagen synthesis of cardiac fibroblasts (CFs) induced by arginine vasopressin (AVP). METHODS: CFs of neonatal Sprague-Dawley rats were isolated by trypsinization and cultured; growth-arrested CFs were stimulated with 1 x 10(-7) mol x L(-1) AVP in the presence or absence of CsA (0.05, 0.5 and 5 micromol x L(-1)). MTT and flow cytometry techniques were adopted to measure cell number and analyze cell cycle respectively. Collagen synthesis was determined by measurement of hydroxyproline content in culture supernatant with colorimetry. Calcineurin activity was estimated by chemiluminescence. Trypan blue staining to test the viability of CFs. RESULTS: 0.05, 0.5 and 5 micromol x L(-1) CsA inhibited the increase of CFs number induced by 1 x 10(-7) mol x L(-1) AVP in a dose-dependent manner, with the inhibitory rates by 12%, 24% and 29%, respectively (P < 0.05). Furthermore, cell cycle analysis showed 0.5 micromol x L(-1) CsA decreased the S stage percentage and proliferation index of CFs stimulated by AVP (P < 0.05). In culture medium, the hydroxyproline content induced by AVP decreased by 0.5 and 5 micromol x L(-1) CsA (P < 0.05), with the inhibitory rates of 29% and 33%, respectively. CsA completely inhibited the increment of calcineurin activity induced by AVP (P < 0.01), but CsA itself had no effect on the baseline of calcineurin activity and CFs viability. CONCLUSION: CsA inhibits proliferation and collagen synthesis of CFs by virtue of blocking calcineurin signaling pathway and might provide a novel target for prevention and treatment to cardiac fibrosis.