INTERFERING HSA_CIRC_0001226 MITIGATES LPS-INDUCED BEAS-2B CELL INJURY BY REGULATING MIR-940/TGFBR2 PATHWAY.

ABSTRACT: Background: Sepsis-associated acute lung injury (SA-ALI) is a serious threat to human health. A growing body of evidence suggested that circular RNAs may be involved in ALI progression. The aim of this study was to investigate the effect and mechanism of circ_0001226 on lipopolysaccharide (LPS)-induced BEAS-2B cells. Methods: BEAS-2B cells were stimulated with LPS to establish a SA-ALI cell model. The expression of circ_0001226, miR-940, and transforming growth factor beta receptor II (TGFBR2) were monitored by quantitative real-time polymerase chain reaction. Cell proliferation and apoptosis were evaluated by the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine assay, and flow cytometry. The levels of interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α were calculated by enzyme-linked immunosorbent assay. Western blot was implemented to test the protein levels of PCNA, Bax, and TGFBR2. Dual-luciferase reporter assay and RNA pull-down assay were adopted to investigate the interaction between circ_0001226 and miR-940, as well as TGFBR2 and miR-940. Results: The levels of circ_0001226 and TGFBR2 were elevated, and miR-940 was decreased in SA-ALI serum specimens and LPS-evoked BEAS-2B cells. Besides that, circ_0001226 interference contributed to cell proliferation and restrained apoptosis and inflammation in LPS-induced BEAS-2B cells. Mechanically, circ_0001226 worked as a molecular sponge of miR-940 to regulate TGFBR2 expression. Conclusion: Circ_0001226 deficiency weakened LPS-mediated proliferation inhibition and inflammatory processes in BEAS-2B cells by binding miR-940 and regulating TGFBR2.

Association between BUN/creatinine ratio and the risk of in-hospital mortality in patients with trauma-related acute respiratory distress syndrome: a single-centre retrospective cohort from the MIMIC database.

OBJECTIVE: Recent studies have shown that blood urea nitrogen to creatinine (BUN/Cr) ratio might be an effective marker for the prognosis of patients with respiratory diseases. Herein, we aimed to assess the association between BUN/Cr ratio and the risk of in-hospital mortality in patients with trauma-related acute respiratory distress syndrome (ARDS). DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: 1034 patients were extracted from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome of the study was in-hospital mortality, defined by the vital status at the time of hospital discharge (ie, survivors and non-survivors). RESULTS: Of the total patients, 191 (18.5%) died in hospital. The median follow-up duration was 16.0 (8.3-26.6) days. The results showed that high level of BUN/Cr ratio was significantly associated with an increased risk of in-hospital mortality (15.54-21.43: HR=2.00, 95% CI: (1.18 to 3.38); >21.43: HR=1.76, 95% CI: (1.04 to 2.99)) of patients with trauma-related ARDS. In patients with trauma-related ARDS that aged ≥65 years old, male and female, Onychomycosis Severity Index (OSI)>98, Revised Trauma Score (RTS)>11, Simplified Acute Physiology Score II (SAPS-II)>37 and sequential organ failure assessment (SOFA) scores≤7, BUN/Cr ratio was also related to the increased risk of in-hospital mortality (all p<0.05). The predictive performance of BUN/Cr ratio for in-hospital mortality was superior to BUN or Cr, respectively, with the area under the curve of receiver operator characteristic curve at 0.6, and that association was observed in age, gender, OSI, RTS, SAPS-II and SOFA score subgroups. CONCLUSION: BUN/Cr ratio may be a potential biomarker for the risk of in-hospital mortality of trauma-related ARDS, which may help the clinicians to identify high-risk individuals and to implement clinical interventions.

Integrated exploration of experimentation and molecular simulation in ester-containing polyimide dielectrics.

With the growing development of film capacitors in various applications, the requirements for polymer dielectrics have increased accordingly. In this work, a series of ester-cotaining polyimide (EPI) dielectrics were designed and fabricated. Futhermore, integrated exploration of experimentation and molecular simulation is proposed to achieve polymer dielectrics with advanced comprehensive performance, as well as to analyze the dielectric mechanism in-depth. The EPIs show superior thermal resistance and dielectric properties. A Weibull breakdown strength of 440-540 MV m-1, permittivity of 3.52-3.85, dissipation factor of 0.627-0.880% and theoretical energy density of 3.13-4.90 J cm-3 were obtained for the EPIs. The relationship between microscopic parameters and dielectric behavior was investigated in detail. According to the experimental and calculated results, there is close correlation between dipolar moment density (µ/V vdw) and dielectric permittivity (ε r). It is deduced that the integrated research of experiments and molecular simulation would be an effective strategy to reveal the dielectric mechanism as well as assist in the molecular design of polymer dielectrics.

Tension zone trapped by exogenous cline: Analysis of a narrow hybrid zone between two parapatric Oxytropis species (Fabaceae).

Hybrid zones have been widely highlighted for their interest in understanding evolutionary processes. It is generally accepted that hybrid zones can be maintained in a balance between dispersal and selection. However, the selective forces can either be endogenous (i.e., genetic incompatibilities between parental taxa) or exogenous (i.e., parental taxa are adapted to different environments). In this study, we evaluated these alternatives and determined the maintenance of a narrow hybrid zone between parapatric distributed Oxytropis diversifolia and O. leptophylla in Nei Mongol, China. For 507 individuals sampled from two populations in the hybrid zone, 12 O. diversifolia populations and five O. leptophylla populations, we measured leaf-morphological characteristics, quantified genetic structure using 11 nuclear microsatellite loci and five chloroplast DNA intergenic regions, collected micro- and macrohabitat data, and conducted geographical cline analysis. We found that the two species differed in leaf morphology, and putative hybrids showed either intermediacy or a bias to O. diversifolia. Parental taxa formed two genetically distinct clusters, while populations in the hybrid zone consisted of both parental forms and various admixed individuals, exhibiting a bimodal pattern. The hybrid zone was coupled to ecological transitions of both microhabitat (i.e., the slope) and macroclimatic conditions. However, the genetic clines were significantly narrower than the environmental cline. Our results indicate that endogenous selection can be primarily responsible for maintaining the hybrid zone, while local adaptation accounts for the position of the zone. We further suggest the probable outcome of hybridization could be introgression.

Synthesis of Single-Layer Two-Dimensional Metal-Organic Frameworks M3 (HAT)2 (M=Ni, Fe, Co, HAT=1,4,5,8,9,12-hexaazatriphenylene) Using an On-Surface Reaction.

1,4,5,8,9,12-Hexaazatriphenylene (HAT) is one of the smallest polyheterocyclic aromatic building blocks for forming conjugated metal-organic frameworks (cMOFs). However, the strong inter-molecular steric hindrance impedes the growth of HAT-based cMOFs. Here we employ on-surface synthesis to grow single-layer two-dimensional cMOFs of M3 (HAT)2 (M=Ni, Fe, Co). Using scanning tunnelling microscopy and density-functional theory (DFT) analysis, we resolve that the frameworks comprise a hexagonal lattice of HAT molecules and a Kagome lattice of metal atoms. The DFT analysis indicates that Ni, Co and Fe carry a magnetic moment of 1.1, 2.5, and 3.7 µB, respectively. We anticipate that the small π-conjugated core of HAT and strong bidentate chelating coordination give rise to appealing electronic and magnetic properties.

Thermally Stable Organic Field-Effect Transistors Based on Asymmetric BTBT Derivatives for High Performance Solar-Blind Photodetectors.

High-performance solar-blind photodetectors are widely studied due to their unique significance in military and industrial applications. Yet the rational molecular design for materials to possess strong absorption in solar-blind region is rarely addressed. Here, an organic solar-blind photodetector is reported by designing a novel asymmetric molecule integrated strong solar-blind absorption with high charge transport property. Such alkyl substituted [1]benzothieno[3,2-b][1]-benzothiophene (BTBT) derivatives Cn-BTBTN (n = 6, 8, and 10) can be easily assembled into 2D molecular crystals and perform high mobility up to 3.28 cm2 V-1 s-1 , which is two orders of magnitude higher than the non-substituted core BTBTN. Cn-BTBTNs also exhibit dramatically higher thermal stability than the symmetric alkyl substituted C8-BTBT. Moreover, C10-BTBTN films with the highest mobility and strongest solar-blind absorption among the Cn-BTBTNs are applied for solar-blind photodetectors, which reveal record-high photosensitivity and detectivity up to 1.60 × 107 and 7.70 × 1014 Jones. Photodetector arrays and flexible devices are also successfully fabricated. The design strategy can provide guidelines for developing materials featuring high thermal stability and stimulating such materials in solar-blind photodetector application.

Interlaminar Fracture Behavior of Carbon Fiber/Polyimide Composites Toughened by Interleaving Thermoplastic Polyimide Fiber Veils.

Carbon fiber reinforced thermosetting polyimide (CF/TSPI) composites were interleaved with thermally stable thermoplastic polyimide (TPPI) fiber veils in order to improve the interlaminar fracture toughness without sacrificing the heat resistance. Both of the mode I and mode II interlaminar fracture toughness (GIC and GIIC) for the untoughened laminate and TPPI fiber veils interleaved laminates were characterized by the double cantilever beam (DCB) test and end notch flexure (ENF) test, respectively. It is found that the TPPI fiber veils interleaved laminates exhibit extremely increased fracture toughness than the untoughened one. Moreover, the areal density of TPPI greatly affected the fracture toughness of laminates. A maximum improvement up to 179% and 132% on GIC and GIIC is obtained for 15 gsm fiber veils interleaved laminate, which contributes to the existence of bicontinuous TPPI/TSPI structure in the interlayer according to the fractography analysis. The interlaminar fracture behavior at elevated temperatures for 15 gsm fiber veils interleaved laminate were also investigated. The results indicated that the introduction of thermally stable TPPI fiber veils could enhance the fracture toughness of CF/TSPI composites by exceeding 200% as compared to the untoughened one even as tested at 250 °C.

Evaluation of a self-management intervention for adults with epilepsy in Taiwan: A longitudinal randomized controlled trial.

PURPOSE: Epilepsy is a neurological disease that causes recurrent seizures and can have a significant impact on a person's quality of life (QOL). A self-management intervention (SMI) can allow adults with epilepsy to modify behaviors in order to manage their seizures and evaluate the impact of medication and treatments on their daily lives. The purpose of this study was to investigate the effects of a SMI for adults with epilepsy. METHODS: This was a longitudinal randomized controlled trial. Adults with epilepsy between the age of 20 and 65 years were recruited from a medical center in northern Taiwan. Participants were assigned to an intervention group (IG) or control group (CG) through simple randomization. Data regarding demographic and clinical characteristics were collected at baseline (T0). In addition, participants answered nine validated self-report questionnaires, which were used as outcome measures. Following collection of baseline data, the CG received routine monthly counseling over the next 3 months. The IG received the routine monthly counseling, as well as individual face-to-face health counseling on self-management 1 h/month and remote counseling via the phone or computer network at least twice per month. After the first month (T1) and at the end of the third (T2) and sixth months (T3) participants answered the nine questionnaires again. Differences in outcomes between the IGs and CGs were analyzed by comparing scores for the nine outcome variables at T0 with scores at T1, T2, and T3 with generalized estimating equations. RESULTS: A total of 210 adults agreed to participate in the study; however, only 155 participants completed the questionnaires for all three time points: 75 in the CG and 80 in the IG. The mean age of the 155 participants was 39.6 years (SD = 10.9). There was no significant difference between demographic or clinical variables between the two groups. The only difference in baseline scores (T0) among the nine self-report questionnaires was in epilepsy knowledge, measured with the Epilepsy Knowledge Profile questionnaire, which were significantly higher for the CG (mean = 32.28, SD = 3.92) than the IG (mean = 23.01, SD = 2.79) (p < 0.001). Generalized estimating equations (GEE) analysis showed scores decreased significantly at T3 from baseline for the CG for epilepsy knowledge and QOL (p < 0.001). Improvements in scores for sleep quality, anxiety, depression, self-efficacy, coping, and social support did not differ between groups. Classification of the IG by gender showed a significantly greater increase for males compared with females from baseline to T3 for epilepsy knowledge (p < 0.001). If we further classified the IGs by seizure frequency, participants with a seizure frequency of ≥1 per year had a more significant increase in epilepsy knowledge and increase in QOL compared with participants with a seizure frequency of <1 per year at T3 compared with T0. CONCLUSION: The lack of improvement in health-related quality of life (HRQoL) following the SMI may indicate that additional time is required to change behaviors that impact this variable for patients with epilepsy. Additional research should focus on variables associated with medication compliance, epilepsy knowledge, medicine symptom distress, self-efficacy, anxiety, and HRQoL.

Porous shape memory scaffold of dextran and hydroxyapatite for minimum invasive implantation for bone tissue engineering applications.

Minimally invasive implantation of a porous scaffold of large volume into bone defect site remains a challenge. Scaffolds based on shape memory polymer (SMP) show potential to be delivered in the compact form via minimally invasive surgery. The present study chooses poly (ε-caprolactone)-diols (PCL-diols) as the SMP to cross-link carboxyl dextran via ester bonds together with particle leaching method to yield a porous SMP scaffold. The inner surfaces of porous SMP scaffold are then mineralized via in situ precipitation to yield mineralized porous SMP-hydroxyapatite (SMP-HA) scaffold. The porous SMP-HA scaffold possesses pore size of 400-500 µm, with HA particles uniformly distributed and orientationally aligned on the inner surfaces of scaffold. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) are carried out to identify the HA deposition. The phase transition temperature of the scaffold is adjusted to 38°C via changing the dosage of PCL (molecule weight: 2800) to endow the scaffold with shape deformation and fixed properties, as well as well-performed shape recovery property under body temperature. Bone marrow mesenchymal stem cells (BMSCs) adhere on the inner surfaces of SMP-HA scaffold, exhibiting larger spreading area when compared to cells adhered on SMP scaffold without HA, promoting its osteogenesis. In vivo degradation showed that the scaffold degrades completely after 6 months post-implantation. At the same time, significant tissue and capillary invasion indicated that the present porous SMP-HA scaffold hold great promise towards bone tissue engineering applications.

LncRNA TUG1 competitively binds to miR-340 to accelerate myocardial ischemia-reperfusion injury.

The aberrant expression of long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) has been previously associated with myocardial ischemia-reperfusion injury (MIRI), but the underlying molecular mechanisms remain elusive. The current study aimed to clarify the functional role of TUG1/microRNA (miR)-340/histone deacetylase 4 (HDAC4)/ß-catenin/glucose transporter type 1 (GLUT1) axes in MIRI. The database-based analyses performed predicted the downstream factors of lncRNA TUG1. In the MIRI mouse models and hypoxia/reoxygenation (H/R)-induced cardiomyocyte models, the expression of TUG1/miR-340/HDAC4/ß-catenin/GLUT1 was manipulated to examine their effects on the infarction area, cardiomyocyte viability and apoptosis employing the Evans blue/TTC double staining, CCK-8 and TUNEL assays. Furthermore, the dual luciferase reporter and RIP assays verified the binding affinity of miR-340 to TUG1 and HDAC4. Subsequently, a negative correlation between miR-340 and TUG1 or HDAC4 expression was identified in myocardial tissues of MIRI mice and H/R-induced cardiomyocyte models, along with a positive correlation between TUG1 and HDAC4. Additionally, it was established that TUG1 bound to miR-340, and miR-340 targeted HDAC4. TUG1 upregulated HDAC4 expression, thereby promoting MIRI in the mouse models. HDAC4 was proven to repress the expression of ß-catenin and its target gene GLUT1. Moreover, the in vivo experiments validated that the inhibition of TUG1/miR-340/HDAC4/ß-catenin/GLUT1 axes alleviated MIRI in mice. Collectively, the current study uncovered the role of TUG1/miR-340/HDAC4/ß-catenin/GLUT1 axes in MIRI mouse models and H/R-induced cardiomyocyte models which may be a potential therapeutic target for MIRI treatment.

Role and Mechanism of Maresin-1 in Acute Lung Injury Induced by Trauma-Hemorrhagic Shock.

BACKGROUND It is reported that trauma hemorrhagic shock (THS) could resulted in organ injury and is related to a high mortality rate. Maresin-1 (MaR1), a derived medium through biosynthesis, is involved in inflammatory responses. However, the mechanism of MaR1 against acute lung injury needs to be further understood. This report aimed to explore whether MaR1 had a protective effect on lung injury. MATERIAL AND METHODS We constructed a THS-induced acute lung damage rat model and then treated the rats with MaR1. We determined Evan's blue dye (EBD) lung permeability, lung permeability index, wet/dry (W/D) weight ratio, nitric oxide (NO) concentration and inducible nitric oxide synthase (iNOS) expression in lung tissue samples. The inflammation-related cytokines levels in the bronchoalveolar lavage fluid (BALF) and serum of rats were determined by enzyme-linked immunosorbent assay (ELISA). Finally, the TLR4/p38MAPK/NF-kappaB pathway was analyzed by quantitative real-time polymerase chain reaction and western blot assay. RESULTS The increased EBD ratio, lung permeability index and W/D weight ratio, NO concentration and iNOS levels were suppressed by MaR1 treatment. THS-induced over-production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in BALF and serum was suppressed by MaR1. Besides, the TLR4/p38MAPK/NF-kappaB pathway activation in THS-induced rats were inhibited by MaR1 treatment. CONCLUSIONS Our study showed that MaR1 could effectively alleviated THS-induced lung injury via inhibiting the excitation of the TLR4/p38MAPK/NF-kappaB pathway in THS-induced rats, suggesting that MaR1 might be a novel agent for lung damage treatment.

High Thermally Stable and Melt Processable Polyimide Resins Based on Phenylethynyl-Terminated Oligoimides Containing Siloxane Structure.

A series of 4-phenylethnylphthalic anhydride (PEPA)-terminated oligoimides were prepared by co-oligomerizing isomeric dianhydrides, i.e., 2,3,3',4'-biphenyltetracarboxylic dianhydride (a-BPDA), 2,3,3',4'-benzophenonetetracarboxylic dianhydride (a-BTDA) or 2,3,3',4'-diphenylethertetracarboxylic dianhydride (a-ODPA), with diamines mixture of bis(4-aminophenoxy)dimethyl silane (APDS) and 2,2'-bis(trifluoromethyl) benzidine (TFDB). The effects of siloxane content and dianhydride structure on the rheological properties of these oligoimides and thermal stability of the corresponding cured polyimide resins were investigated. The results indicated that the introduction of the siloxane structure improved the melt processability of the oligoimides, while the thermal stability of the cured polyimide resins reduced. The oligoimide derived from a-ODPA revealed better melt processability and melt stability due to the existence of a flexible dianhydride structure. The oligoimide PIS-O10 derived from a-ODPA gave the lowest minimum melt viscosity of 0.09 Pa·s at 333 °C and showed the excellent melt stability at 260 °C for 2 h with the melt viscosity in the range of 0.69-1.63 Pa·s. It is also noted that the thermal stability of these resins can be further enhanced by postcuring at 400-450 °C, which is attributed to the almost complete chemical crosslinking of the phenyethynyl combined with oxidative crosslinking of siloxane. The PIS-T10 and PIS-O10 resins that were based on a-BTDA and a-ODPA, respectively, even showed a glass transition temperature over 550 °C after postcuring at 450 °C for 1 h.

CCM1 and CCM2 variants in patients with cerebral cavernous malformation in an ethnically Chinese population in Taiwan.

Cerebral cavernous malformation (CCM) is a vascular malformation characterized by clustered enlarged capillary-like channels in the central nervous system. The genes harboring variants in patients with CCM include CCM1/Krev interaction trapped-1, CCM2/MGC4607, and CCM3/programmed cell death protein 10. We aimed to identify pathogenic variants in an ethnic Chinese population in Taiwan. We recruited 95 patients with multiple CCMs or a single lesion with a relevant family history. Sanger sequencing was performed for 41 patients. Variants were identified using sequence alignment tools, and the clinical significance of these variants was determined using American College of Medical Genetics and Genomics standards and guidelines. Several pathogenic variants were found in six patients, including three unrelated patients and three affected members of one family. Two novel pathogenic variants leading to early truncation comprised a deletion variant in exon 18 of CCM1 (c.1846delA; p.Glu617LysfsTer44) and an insertion variant in exon 4 of CCM2 (c.401_402insGCCC; p.Ile136AlafsTer4). One novel pathogenic splice site variant was c.485 + 1G > C at the beginning of intron 8 of CCM1. In this study, we identified novel variants related to CCM in an ethnically Chinese population in Taiwan.

[Integration of clinical pathway construction and hospital information system in intensive care unit is the core of digitalized hospital: experience of clinical pathway construction in Liuzhou Worker's Hospital from 2016 to 2018].

OBJECTIVE: To explore the effective strategies of clinical pathway construction in intensive care unit (ICU). METHODS: From January 2016 to July 2018, 1 488 patients were discharged from ICU of Liuzhou Worker's Hospital of Guangxi Zhuang Autonomous Region. The pilot project of "postoperative monitoring of heart disease" with simpler route and less variation was selected first, and then the pilot project was promoted to "post-operative monitoring" after its success. The implementation of the clinical pathway was divided into three stages: the first stage, January 2016 to May 2017, for the pilot phase, a total of 87 patients were enrolled in the clinical pathway trial; the second stage, June 2017 to December 2017, surgical ICU "postoperative monitoring of heart disease" was put into the pathway 111 times; the third stage, January 2018 to July 2018, surgical ICU "postoperative monitoring of heart disease" was entered in the path 116 times; comprehensive ICU "postoperative care" was put into the path 96 times. After carefully analyzed the reasons and sum up the experience, internet+medical treatment (Liuzhou Worker's Hospital became the fifth deep partner of Tencent Inc in the internet+medical field, and carried out the plan and practice of "WeChat wisdom hospital 3.0" in 2017) was used, four aspects of connection, payment, security and ecological cooperation were upgraded, and the construction of 6 level of electronic medical record (EMR) was accelerated. At the same time, through diagnosis related groups system (DRGs), the concept of evidence-based medicine, quality management and continuous improvement as the leading factor, and combined with the construction status of hospital information system (HIS) and EMR system, step by step implementation and design of information management platform for clinical pathway were formulated. The completion rate of clinical pathway, average length of hospital stay, average cost, cure rate and improvement rate were the main observation parameters. RESULTS: In the first stage, none of the 87 patients who entered the clinical pathway completed the clinical pathway. In the second stage, the completion rate of surgical ICU clinical pathway was increased from 33.33% in June 2017 to 94.44% in December 2017, and up to 100% in October 2017, and the average completion rate from January to July 2018 was 94.00%. The completion rate of ICU clinical pathway was increased from 81.82% in January 2008 to 92.86% in July 2008. There was a significant difference in the overall clinical pathway completion rate from 2016 to 2018 (χ2 = 204.300, P = 0.000). After the effective implementation of clinical pathway in June 2017, the length of hospital stay of patients was significantly shortened as compared with that before implementation (days: 2.96±0.43 vs. 6.66±0.75, P < 0.01), and the daily cost was significantly reduced (Yuan: 3 550.92±755.51 vs. 6 171.48±377.29, P < 0.01). The average length of hospital stay was shortened by about 3.84 days (P < 0.01), and the average daily cost was reduced by about 2 108.39 Yuan (P < 0.01) after the implementation of clinical pathway by surgical ICU "postoperative monitoring of heart disease" as compared with those before implementation. The average length of hospital stay was shortened by about 2.98 days (P < 0.01) and the average daily cost was reduced by 5 094.13 Yuan (P < 0.01) after the implementation of clinical pathway by comprehensive ICU "post-operative monitoring" as compared with those before implementation. At the same time, the cure rate was increased from 1.16% (7/603) to 42.26% (105/227), and the improvement rate was decreased from 94.36% (569/603) to 52.86% (120/227, both P < 0.01) after the implementation of surgical ICU clinical pathway, but there was no significant difference in the cure rate or the improvement rate after the implementation of comprehensive ICU [2.77% (33/1 193) vs. 2.22% (2/90), 79.21% (945/1 193) vs. 97.78% (88/90), both P > 0.05]. CONCLUSIONS: Application of clinical pathway to control ICU quality and guide diagnosis and treatment, more refined diagnosis and treatment schemes including clinical guidelines, average length of stay, average cost of hospitalization, cost-efficiency ratio and so on were completed, which confirmed that the improvement of clinical pathway management strategy originated from clinical were needed. Informatization, intellectualization, standardization and effective control of medical cost of clinical pathway could improve medical quality and accurate management. The integration of ICU clinical pathway construction and HIS could promote the development of digital hospitals.

Inhibition of Src by microRNA-23b increases the cisplatin sensitivity of chondrosarcoma cells.

Chondrosarcomas are malignant cartilage-forming tumors from low-grade to high-grade aggressive tumors characterized by metastasis. Cisplatin is an effective DNA-damaging anti-tumor agent for the treatment against a wide variety of solid tumors. However, chondrosarcomas are notorious for their resistance to conventional chemo- and radio- therapies. In this study, we report miR-23b acts as a tumor suppressor in chondrosarcoma. The expressions of miR-23b are down-regulated in chondrosarcoma patient samples and cell lines compared with adjacent normal tissues and human primary chondrocytes. In addition, overexpression of miR-23b suppresses chondrosarcoma cell proliferation. By comparison of the cisplatin resistant chondrosarcoma cells and parental cells, we observed miR-23b was significantly down regulated in cisplatin resistant cells. Moreover, we demonstrate here Src kinase is a direct target of miR-23b in chondrosarcoma cells. Overexpression of miR-23b suppresses Src-Akt pathway, leading to the sensitization of cisplatin resistant chondrosarcoma cells to cisplatin. This chemo-sensitivity effect by the miR-23b-mediated inhibition of Src-Akt pathway is verified with the restoration of Src kinase in miR-23b-overespressing chondrosarcoma cells, resulting in the acquirement of resistance to cisplatin. In summary, our study reveals a novel role of miR-23b in cisplatin resistance in chondrosarcoma and will contribute to the development of the microRNA-targeted anti-cancer therapeutics.

Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians.

OBJECTIVE: To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai). METHODS: We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)-induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database. RESULTS: We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6 drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10-10; odds ratio 27.90; 95% confidence interval [CI] 7.84-99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077-0.584). CONCLUSIONS: Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further.

Factors affecting quality of life in adults with epilepsy in Taiwan: A cross-sectional, correlational study.

PURPOSE: The purpose of this study was to assess eight factors considered important for quality of life in persons with epilepsy in order to determine which of these components affect quality of life in adults with epilepsy in Taiwan. METHODS: A cross-sectional, correlational study using structured questionnaires assessed 260 patients with epilepsy purposively sampled from a medical center in Northern Taiwan. Health-related quality of life (HRQoL) was evaluated with the Quality of Life in Epilepsy-31 (QOLIE-31) questionnaire. Data also included personal and health-related characteristics, knowledge of epilepsy, efficacy in the self-management of epilepsy, and social support. RESULTS: Scores for the QOLIE-31 were correlated with the following factors: (1) demographic characteristics of age, gender, and income; (2) sleep quality; (3) symptoms of anxiety and depression; (4) epilepsy-specific variables: seizure frequency; types, number, and frequency of antiepileptic drugs (AEDs); and adverse events of AEDs; and (5) social support. Stepwise regression analysis showed that seven factors were predictive for quality of life: anxiety, depression, adverse events of AEDs, social support, seizure frequency of at least once in three months, household income of NT$ 40,001-100,000, and male gender. These factors accounted for 58.2% of the variance of quality of life. SIGNIFICANCE: Our study assessed multiple factors in an examination of relationships and predictive factors for quality of life in adults with epilepsy in Taiwan. Knowledge of these contributing factors can assist health-care providers when evaluating patients with epilepsy to help target interventions for improving quality of life.

Genetic variants associated with phenytoin-related severe cutaneous adverse reactions.

IMPORTANCE: The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. OBJECTIVE: To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. MAIN OUTCOMES AND MEASURES: Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. RESULTS: The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10(-17)). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P < .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease. CONCLUSIONS AND RELEVANCE: This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.

Genotype-phenotype association between HLA and carbamazepine-induced hypersensitivity reactions: strength and clinical correlations.

BACKGROUND: Increasing studies reported genetic susceptibility to drug hypersensitivity reactions, as exemplified by the HLA-A*31:01 and HLA-B*15:02 association with carbamazepine (CBZ)-induced hypersensitivity reactions, such as maculopapular exanthema (MPE), drug rash with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). OBJECTIVE: To carry out a comprehensive analysis on the clinical spectrum and HLA genotype-phenotype correlations in CBZ-induced hypersensitivity reactions. METHODS: We analyzed the clinical information of 194 patients with CBZ hypersensitivity (51 MPE, 23 DRESS, 112 SJS/TEN, and 8 cases with other phenotypes), and 152 CBZ-tolerant controls. All are Han Chinese. We examined the HLA-A/HLA-B genotypes, gene dosage, and drug dosage effects. RESULTS: CBZ-SJS/TEN showed the strongest association with the HLA-B*15:02 allele (Pc=5.8×10(-43); odds ratio (OR) (95% CI)=97.6(42.0-226.8)), in which HLA-B*15:02 was identified in all patients (25/25) with SJS/TEN with >5% body surface area (BSA) skin detachment, but lost its 100% association (85.1%, 74/87) in SJS with <5% BSA detachment. In contrast, HLA-B*40:01 showed negative association with CBZ-induced SJS/TEN ((Pc=8.3×10(-5); OR (95% CI)=0.22(0.1-0.4)). By comparison, CBZ-induced MPE/DRESS had no association with HLA-B*15:02, but linked to HLA-A*31:01 (Pc=2.7×10(-3); OR (95% CI)=6.86(2.4-19.9), and HLA-B*51:01 (Pc=0.01; OR (95% CI)=4.56(2.0-10.5)). No gene dosage or CBZ dosage effects was observed. CONCLUSION: This study reported the different strength of HLA association with CBZ hypersensitivity in Han Chinese. With the increasing application of pharmacogenetic markers, the HLA genotype-phenotype correlations and the results of the test need to be carefully interpreted for CBZ-induced hypersensitivity reactions.

Copper-catalyzed aromatic C-H bond halogenation with lithium halides under aerobic conditions.

A concise and practical Cu-catalyzed protocol for the preparation of chloro- and bromoarenes via C-H bond activation has been developed. The advantages of this strategy are the employment of cheap Cu(NO3)2·3H2O, LiX and O2, and its compatibility with both electron-donating and electron-withdrawing substituents on aryl rings.