Drug closed-loop management system using mobile technology.

BACKGROUND: Drug closed-loop management reflects the level of hospital management and pharmacist service. It is a challenge for hospital pharmacists to realize the whole-process closed-loop management of drugs in hospital pharmacies. Therefore, this study aimed to evaluate the operational effect of using mobile technology to build a closed-loop drug management system. METHODS: Using mobile technology, replacing the traditional paper dispensing model and constructing a multinode information collection system according to the Healthcare Information and Management Systems Society Standard, we reformed the hospital information system and inpatient pharmacy workflow and then evaluated the new approach using statistical methods. RESULTS: After the transformation, the entire process of drug data can be traced. Closed-loop management, as well as real-time data verification and control, thereby improves the work efficiency and reduces the drug dispensing time. By reducing the work error rate, the number of dispensing errors decreased from 5 to 1 case/month. The comprehensive dispensing process can achieve the whole workflow of paperless operation and reduce the use of paper A4 by 180,000 pieces per year. CONCLUSIONS: Mobile technology can improve the service level of pharmacies, enhance the level of drug management and hospital quality management, ensure the safety of medication for inpatients, and significantly reduce the amount of paper used.

Long intergenic noncoding RNA SNHG16 interacts with miR-195 to promote proliferation, invasion and tumorigenesis in hepatocellular carcinoma.

Long non-coding RNAs (lncRNAs) have been confirmed crucial regulators in tumorgenesis. Small nucleolar RNA host gene 16 (SNHG16) has been recently shown to be dysregulated, which uncovered to be a potential oncogene in some cancers. However, the biological function and potential mechanism of SNHG16 in hepatocellular carcinoma (HCC) remain unclear. In our study, our observations showed that the expression level of SNHG16 in HCC tissues and cell lines was upregulated compared with adjacent noncancerous tissues and normal cells. In vitro, loss-of-function experiments revealed that SNHG16 knockdown suppressed the proliferation and weakened invasion of SMMC7721 and HepG2 cells. miR-195 expression was significantly decreased in HCC tissues and negatively correlated with SNHG16 expression. Furthermore, RIP and dual luciferase reporter assays showed that SNHG16 acted as an endogenous sponge by directly binding to miR-195 and downregulated its expression. SNHG16 overexpression inverted the inhibitory effect of miR-195 on proliferation and invasion of SMMC7721 and HepG2 cells. Additionally, SNHG16 depletion resulted in lower tumor growth and weight loss, in vivo. In conclusion, our findings reported that the oncogenic role of SNHG16 in HCC tumorigenesis through a novel SNHG16-miR-195 axis, which provided a novel insight for HCC and helped to probe a potential therapeutic target for the deadly disease.

Knockdown of SUMO1P3 represses tumor growth and invasion and enhances radiosensitivity in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with high recurrence and metastasis rates. Radiotherapy represents a major therapeutic option for HCC patients. However, the efficacy of radiotherapy has been limited due to the development of intrinsic radioresistance of the tumor cells. Small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3), one member of SUMO pseudogene family, is a novel identified lncRNA that was originally identified to be upregulated in gastric cancer. However, the detailed roles of SUMO1P3 in HCC development remain to be elucidated. Here, the expression of SUMO1P3 in HCC tissues and cells was examined by qRT-PCR. Cell proliferation, colony formation ability, invasion ability, apoptosis, and radiosensitivity were detected by MTT assay, colony formation assay, cell invasion assay, flow cytometry analysis, and survival fraction assay, respectively. We found that SUMO1P3 was significantly upregulated in HCC tissues and cells. Besides, SUMO1P3 was highly expressed in HCC patients with higher TNM stage. Furthermore, SUMO1P3 knockdown markedly suppressed cell proliferation, colony formation ability, and cell invasiveness, promoted apoptosis, and enhanced radiosensitivity of HCC cells. We concluded that the knockdown of SUMO1P3 repressed tumor growth, invasion, promoted apoptosis, and enhanced radiosensitivity in HCC, providing evidence that SUMO1P3 might be a potential novel biomarker and a therapeutic target for HCC.

MiR-19a Affects Hepatocyte Autophagy via Regulating lncRNA NBR2 and AMPK/PPARα in D-GalN/Lipopolysaccharide-Stimulated Hepatocytes.

This study aims to evaluate the potential involvement and regulatory mechanism of miR-19a in hepatocytes autophagy of acute liver failure (ALF). The in vitro hepatocytes injury model of primary hepatocyte and hepatocytes line HL-7702 was established by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) co-treatment. Relative expression level of miR-19a and NBR2 was determined by qRT-PCR. Protein expression of AMPK/PPARα and autophagy-related gene was determined by Western blot. In hepatic tissue of 20 ALF patients and D-GalN/LPS-stimulated hepatocytes, miR-19a was upregulated and NBR2 was downregulated. D-GalN/LPS stimulation caused the inactivation of AMPK/PPARα signaling and the decrease of autophagy-related LC3-II/LC3-I ratio and beclin-1 expression in hepatocytes. The expression of both AMPK/PPARα and NBR2 were negatively controlled by miR-19a overexpression or knockdown. Moreover, both NBR2 and PPARα were targeted regulated by miR-19a according to luciferase reporter assay. In D-GalN/LPS-stimulated hepatocytes, AMPK activation promoted PPARα expression. AMPK inactivation inhibited the pro-autophagy effect of miR-19a and caused the decrease of LC3-II/LC3-I ratio and beclin-1 expression. PPARα activation abrogated the anti-autophagy effect of miR-19a mimic and caused the increase of LC3-II/LC3-I ratio and beclin-1 expression. NBR2 knockdown reversed the anti-autophagy impact of miR-19a inhibitor and caused the decrease of LC3-II/LC3-I ratio and beclin-1 expression. In summary, our data suggested that miR-19a negatively controlled the autophagy of hepatocytes attenuated in D-GalN/LPS-stimulated hepatocytes via regulating NBR2 and AMPK/PPARα signaling. J. Cell. Biochem. 119: 358-365, 2018. © 2017 Wiley Periodicals, Inc.

Hepatitis B virus X protein promotes proliferation of hepatocellular carcinoma cells by upregulating miR-181b by targeting ING5.

Hepatitis B virus X protein (HBx) played a key role in the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Emerging evidence has demonstrated that miR-181b and the inhibitor of growth protein 5 (ING5) participated in the pathophysiological process. However, the regulatory mechanism of HBx remained unknown. The expression of miR-181b and ING5 in HCC tissues and cell lines were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell viability was determined using the MTT method following HCC cell lines transfection. The interaction between miR-181b and ING5 was assessed by luciferase reporter assay. The nude mice tumor model was well established to evaluate the role and biological functions of HBx on the progression of HBV-related HCC in vivo. MiR-181b was upregulated and ING5 was downregulated in HCC tissues and cell lines. As suggested by the results from in vitro and in vivo experiments, HBx downregulates the expression of the miR-181b target gene ING5, resulting in the promotion of HCC cell proliferation. HBx accelerates proliferation activity of HCC cells by increasing miR-181b expression via targeting ING5, thereby influencing the progression of HBV-related HCC.

Influence of Pseudomonas aeruginosa pvdQ gene on altering antibiotic susceptibility under swarming conditions.

In Pseudomonas aeruginosa PAO1, the pvdQ gene has been shown to have at least two functions. It encodes the acylase enzyme and hydrolyzes 3-oxo-C12-HSL, the key signaling molecule of quorum sensing system. In addition, pvdQ is involved in swarming motility. It is required and up-regulated during swarming motility, which is triggered by high cell densities. As high density bacterial populations also display elevated antibiotics resistance, studies have demonstrated swarm-cell differentiation in P. aeruginosa promotes increased resistance to various antibiotics. PvdQ acts as a signal during swarm-cell differentiation, and thus may play a role in P. aeruginosa antibiotic resistance. The aim of this study was to examine whether pvdQ was involved in modifying antibiotic susceptibility during swarming conditions and to investigate the mechanism by which this occurred. We constructed the PAO1pMEpvdQ strain, which overproduces PvdQ. PAO1pMEpvdQ promotes swarming motility, while PAO1ΔpvdQ abolishes swarming motility. In addition, both PAO1 and PAO1pMEpvdQ acquired resistance to ceftazidime, ciprofloxacin, meropenem, polymyxin B, and gentamicin, though PAO1pMEpvdQ exhibited a twofold to eightfold increase in antibiotic resistance compared to PAO1. These results indicate that pvdQ plays an important role in elevating antibiotic resistance via swarm-cell differentiation and possibly other mechanisms as well. We analyzed outer membrane permeability. Our data also suggest that pvdQ decreases P. aeruginosa outer membrane permeability, thereby elevating antibiotic resistance under swarming conditions. Our results suggest new approaches for reducing P. aeruginosa resistance.

Intracellular Staphylococcus aureus-induced NF-κB activation and proinflammatory responses of P815 cells are mediated by NOD2.

Staphylococcus aureus (S. aureus) is an important human pathogen which can cause a chronic condition with a high relapse rate despite the aggressive antimicrobial treatment. Recent studies showed that intracellular pattern recognition receptors (including NOD) in response to bacteria or bacterial products play a proinflammatory role by activating nuclear transcription factor-κB (NF-κB). But how NOD2 mediates the proinflammatory response to S. aureus in mast cells (MCs) is unclear. So, in this study, we attempted to examine the role of NOD2 in inflammatory responses of MCs to S. aureus. P815 cells (a mouse mast cell line) were cultured. Real-time PCR was used to detect the NOD2 mRNA expression in P815 cells during S. aureus infection. The siRNA against NOD2 gene was synthesized and transfected into S. aureus-infected P815 cells. By using the methods of ELISA and flow cytometry, the effects of NOD2 gene silencing on cell phagocytosis, cytokine secretion, NF-κB activation and cell apoptosis of the S. aureus-infected P815 cells were examined. It was found that S. aureus infection could increase the expression of NOD2 mRNA in P815 cells. NOD2 gene interference in P815 cells reduced the number of S. aureus engulfed by P815 cells, the level of cytokines and the activation of NF-κB. In addition, S. aureus could induce the apoptosis of P815 cells, but NOD2 gene silencing did not affect the cell apoptosis rate. Our data suggested that NOD2 plays a key role in pathogen recognition, signal transduction, and NF-κB activation in the inflammatory responses of MCs infected by S. aureus.

Influence of Pseudomonas aeruginosa pvdQ gene on altering antibiotic susceptibility under swarming conditions.

In Pseudomonas aeruginosa PAO1, the pvdQ gene has been shown to have at least two functions. It encodes the acylase enzyme and hydrolyzes 3-oxo-C12-HSL, the key signaling molecule of quorum sensing system. In addition, pvdQ is involved in swarming motility. It is required for up-regulated during swarming motility, which is triggered by high cell densities. As high-density bacterial populations also display elevated antibiotic resistance, studies have demonstrated that swarm-cell differentiation in P. aeruginosa promotes increased resistance to various antibiotics. PvdQ acts as a signal during swarm-cell differentiation, and thus may play a role in P. aeruginosa antibiotic resistance. The aim of this study is to examine whether pvdQ was involved in modifying antibiotic susceptibility during swarming conditions, and to investigate the mechanism by which this occurred. We constructed the PAO1pMEpvdQ strain, which overproduced PvdQ. PAO1pMEpvdQ promotes swarming motility, while PAO1ΔpvdQ abolishes swarming motility. In addition, both PAO1 and PAO1pMEpvdQ acquired resistance to ceftazidime, ciprofloxacin, meropenem, polymyxin B, and gentamicin, though PAO1pMEpvdQ exhibited a two to eightfold increase in antibiotic resistance compared to PAO1. These results indicate that pvdQ plays an important role in elevating antibiotic resistance via swarm-cell differentiation and possibly other mechanisms as well. We analyzed outer membrane permeability. Our data also suggest that pvdQ decreases P. aeruginosa outer membrane permeability, thereby elevating antibiotic resistance under swarming conditions. Our results suggest new approaches for reducing P. aeruginosa resistance.

Pseudomonas aeruginosa pvdQ gene prevents Caco-2 cells from obstruction of quorum-sensing signal.

Quorum sensing (QS) system plays an important role in bacterial pathopoiesis of incurable Pseudomonas aeruginosa infection, which strongly warrants new strategies for absence of curative treatment to date. Latest investigations show that pvdQ gene of P. aeruginosa can attenuate the pathopoiesis of the bacteria by encoding acylase enzyme and hydrolyze N-(3-oxododecanoyl)-Homoserine Lactone (3O-oxo-C(12)-HSL), the key signal molecule of QS system. This study tries to resist the pathogenicity of P. aeruginosa by transfecting human intestinal epithelial Caco-2 cells with pvdQ gene. We found that 3O-oxo-C(12)-HSL was decreased in the supernatant of cells transfected with pvdQ gene. Moreover, the result of flow cytometry showed that the 3O-oxo-C(12)-HSL evoked apoptosis rate of Caco-2 cells was inhibited when the cells were transfected with pvdQ gene. In contrast, the control result displayed increased Caco-2 cells' apoptosis rate after stimulation of 3O-oxo-C(12)-HSL without protection of pvdQ gene. In conclusion, we successfully protect mammalian cells Caco-2 from injure of QS signal molecule 3O-oxo-C(12)-HSL through imputing pvdQ gene, which may suggest a new therapeutic strategy for P. aeruginosa infection.

Influence of Pseudomonas aeruginosa quorum sensing signal molecule N-(3-oxododecanoyl) homoserine lactone on mast cells.

Quorum sensing system is a cell-to-cell communication system that plays a pivotal role in virulence expression in bacteria. Recent advances have demonstrated that the Pseudomonas aeruginosa quorum sensing molecule, N-3-oxododecanoyl homoserine lactone (3OC(12)-HSL), exerts effects on mammalian cells and modulates host immune response. Mast cells (MCs) are strategically located in the tissues that are constantly exposed to external stimulus. Therefore, it is very much possible that 3OC(12)-HSL may interact with MCs. Little is known, however, about specific effects of 3OC(12)-HSL on MCs. To address this, we investigated the influence of 3OC(12)-HSL on cell viability, apoptosis, intracellular calcium and cytokine release in MCs. We found that at high concentrations (100 microM), 3OC(12)-HSL inhibited proliferation and induced apoptosis in P815. The 3OC(12)-HSL treatment significantly increased intracellular calcium release in both P815 and HMC-1. We also observed that 3OC(12)-HSL-induced histamine release and degranulation in HMC-1 cells. Furthermore, 3OC(12)-HSL-induced IL-6 production at lower concentrations (6.25-12.5 microM) but steadily reduced IL-6 production at high concentration (50-100 muM). These data demonstrate that P. aeruginosa 3OC(12)-HSL affects MCs function.

Sodium tanshinone IIA sulfonate inhibits proliferation, migration, invasion and inflammation in rheumatoid arthritis fibroblast-like synoviocytes.

Our study aimed to determine the effects of sodium tanshinone IIA sulfonate (STS) on proliferation, migration, invasion, and inflammation in rheumatoid arthritis human fibroblast-like synoviocytes (RA-HFLSs). Firstly, results demonstrated STS reduced proliferation, migration, invasion in HFLSs. Also, we found that STS could alleviate the reorganizations of F-actin cytoskeleton in TNF-α-treated HFLSs. In addition, STS decreased the production of IL-1ß, IL-6, MMP-1, and MMP-3 in TNF-α-treated RA-HFLSs. Further study showed that STS blocked MAPK/NF-κB activations in TNF-α-stimulated RA-HFLSs. Moreover, we illustrated that STS could alleviate rheumatoid arthritis progression and prevent inflammation damage in joint tissues of collagen-induced arthritis (CIA) mice. Taken together, this study suggested that STS inhibited proliferation, migration, invasion, and inflammation of RA-HFLSs by blocking MAPK/NF-κB pathways.

Protective effects of cilostazol on ethanol-induced damage in primary cultured hepatocytes.

Alcoholic liver disease (ALD) caused by excessive alcohol consumption is associated with oxidative stress, mitochondrial dysfunction, and hepatocellular apoptosis. Cilostazol, a licensed clinical drug used to treat intermittent claudication, has been reported to act as a protective agent in a spectrum of diseases. However, little information regarding its role in ethanol-induced hepatocellular toxicity has been reported. In the current study, we investigated the protective effects and mechanisms of cilostazol on ethanol-induced hepatocytic injury. Rat primary hepatocytes were pretreated with cilostazol prior to ethanol treatment. MTT and LDH assay indicated that ethanol-induced cell death was ameliorated by cilostazol in a dose-dependent manner. Our results display that overproduction of intracellular reactive oxygen species (ROS) and 4-hydroxy-2-nonenal (4-HNE) induced by ethanol was attenuated by pretreatment with cilostazol. Furthermore, cilostazol significantly inhibited ethanol-induced generation of ROS in mitochondria. Importantly, it was shown that cilostazol could improve mitochondrial function in primary hepatocytes by restoring the levels of ATP and mitochondrial membrane potential (MMP). Additionally, cilostazol was found to reduce apoptosis induced by ethanol using a terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Mechanistically, we found that cilostazol prevented mitochondrial pathway-mediated apoptotic signals by reversing the expression of Bax and Bcl2, the level of cleaved caspase-3, and attenuating cytochrome C release. These findings suggest the possibility of novel ALD therapies using cilostazol.

Anti-HBV effect of interferon-thymosin α1 recombinant proteins in transgenic Dunaliella salina in vitro and in vivo.

The aim of the present study was to investigate the anti-hepatitis B virus (HBV) effect of interferon (IFN)-thymosin α1 (TA1) in a transgenic Dunaliella salina (TDS) system in vitro and in vivo. The toxicity of TDS in the HepG2.2.15 cell line was assessed using an MTT assay. The effect of TDS on the secretion of HBV early antigen (HBeAg) and HBV surface antigen (HBsAg) in culture supernatants was measured using ELISA. In addition, HBV-DNA was analyzed using quantitative polymerase chain reaction. Drug treatment experiments were performed in vivo on ducks congenitally infected with duck HBV (DHBV). The drug was administered once daily for 21 continuous days. Blood was drawn from all ducks prior to treatment, following treatment for 7, 14 and 21 days, and following drug withdrawal for 5 days. Serum DHBV-DNA was determined using quantitative PCR. In addition, the histology of duck liver tissues was assessed using hematoxylin and eosin, and orcein staining. The results demonstrated that TDS suppressed cell viability and HBsAg and HBeAg secretion in HepG2.2.15 cells. Furthermore, the treatment index values for HBsAg and HBeAg following TDS treatment were 2.96 and 3.07 respectively, which were greater than those of the IFN-α treated group. In addition, the DHBV-infected duck model experiments indicated that serum DHBV-DNA levels were significantly decreased in the group of TDS (20 g/kg) following treatment for 7, 14 and 21 days compared with the control group. Following withdrawal of the drug for 5 days, the levels of DHBV-DNA did not relapse in the medium and high dose groups of TDS (10 and 20 g/kg, respectively). Histological analysis of duck liver also demonstrated that TDS and IFN-α treatment alleviated inflammation and HBsAg signals in duck livers. In conclusion, TDS markedly suppresses HBV replication in vitro and in vivo and its anti-HBV effect is greater than that of IFN-α.

Involvement of PI3K/Akt pathway in the inhibition of hepatocarcinoma cell invasion and metastasis induced by SASH1 through downregulating Shh-Gli1 signaling.

The SASH1 gene is discovered as a tumor suppressor recently. However, the molecular mechanisms of SASH1 in hepatocarcinoma (HCC) remain unclear. In present studies, we investigated the molecular mechanisms of SASH1 on cell invasion and metastasis of hepatocarcinoma in vivo and in vitro. In this study, SASH1 overexpression HCC cell lines were treated with purmorphamine (0, 0.5, 1, 2µmol/l). Western blot and qRT-PCR were used to examine the related gene expression of EMT markers and the Shh-Gli1 and PI3K/Akt-dependent pathway. Cell migration and invasion were assessed by Transwell assay. In addition, a mice SASH1 overexpression HCC orthotopic xenograft model was established and treated with purmorphamine or 740Y-P or PDGF. Tumor volume was assessed, and H&E staining was applied to histopathologic analysis. The results showed that purmorphamine exposure significantly increased the mRNA and protein expression levels of Shh and Gli1 in a dose-dependent manner in the SASH1 overexpression HepG2 and HCCLM3 cells. Besides, purmorphamine promoted the migration and invasion of SASH1 overexpression HCC cells, as well as the EMT progress. Moreover, purmorphamine significantly increased the synthesis of PI3K and pAkt in a dose-dependent manner. Furthermore, the invasion and migration abilities were also improved by treatment with 740Y-P or PDGF in the SASH1 overexpression HCC cells. Additionally, the agonists promoted tumor growth and intrahepatic and pulmonary metastasis of the orthotopic transplantation tumors grown from SASH1 overexpression HCC cells in vivo. In conclusion, SASH1 may inhibit hepatocarcinoma cell invasion and metastasis through down-regulating the Shh-Gli1 and PI3K-AKT pathways in vivo and in vitro.

Quality of life in adolescent patients with idiopathic scoliosis after brace treatment: A meta-analysis.

BACKGROUND: Whether brace-treated adolescents with idiopathic scoliosis (AIS) have improved quality of life (QoL) is still unknown. Thus, we conducted a meta-analysis to compare the QoL of brace-treated AIS patients with untreated AIS patients. The pain, self-image/appearance, mental health, function/activity, satisfaction with management, total score without satisfaction, and total score of patients were used to measure the QoL after the intervention. METHODS: Multiple electronic databases including PubMed, Web of Science, and Embase were searched for all years up to June 30, 2016. Articles in English that used the Scoliosis Research Society-22 (SRS-22) or a modified version of the SRS-22 questionnaire to evaluate the QoL differences between brace-treated AIS patients and untreated AIS patients were included in the meta-analysis. The Newcastle-Ottawa Scale was used in the quality of literature evaluation. The pooled standardized mean difference (SMD) with its corresponding 95% confidence interval (CI) for each parameter was computed. Egger test and Begg test were used to test for publication bias. RESULTS: The SRS-22 or a modified SRS-22 questionnaire was used to evaluate the QoL after surgery. There was no significant difference in pain (SMD = 0.123, 95% CI: -0.101 to 0.347, P = .282), self-image/appearance (SMD = 0.108, 95% CI: -0.116 to 0.332, P = .334), mental health (SMD = 0.031, 95% CI: -0.130 to 0.201, P = .365), function/activity (SMD = 0.202, 95% CI: -0.022 to 0.425, P = .077), and total score without satisfaction (SMD = 0.123, 95% CI: -0.232 to 0.478, P = .497) between the untreated (observation) and brace-treated AIS patients, whereas a significant difference was observed in satisfaction with management (SMD = 0.393, 95% CI: 0.127-0.659, P = .004) and total score (SMD = 0.312, 95% CI: 0.054-0.571, P = .018) between the 2 groups. CONCLUSION: Our meta-analysis indicated that brace-treated AIS patients had a higher QoL. However, further analysis could not be performed because of insufficient data, such that we were unable to make subgroup analysis of QoL for different types of AIS and the therapeutic methods chosen by brace-treated AIS patients.

Regulation of the oncogenic function of distal-less 4 by microRNA-122 in hepatocellular carcinoma.

Distal-less 4 (DLX4) is a member of the DLX family of homeobox genes. Recent reports have suggested that abnormal expression of DLX4 is present in several types of human tumors, including breast cancer, leukemia and colon cancer. However, the function and the mechanistic regulation of DLX4 in hepatocellular carcinoma (HCC) are elusive. In the present study, a proportion of hepatocellular carcinomas were identified to exhibit upregulated DLX4 expression. This study proposed that the overexpression of DLX4 is associated with the downregulation of miR-122, an underexpressed miRNA in human HCC. Functional studies have demonstrated that the downregulation of DLX4 in hepatocellular carcinoma cell lines is regulated by miR-122 through binding to its 3'UTR. Furthermore, a DLX4 overexpression vector lacking the 3'UTR was shown to abolish miR-122-induced inhibition of proliferation in the HCC cell line Hep3B. These results gave new insight into the mechanism of the miR-122/DLX4 axis in HCC.