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Background Current polymyxin B dosing in children relies on scant data. Objectives To build a population pharmacokinetic (PK) model for polymyxin B in paediatric patients and assess the likely appropriateness of different dosages. Methods A total of 19 paediatric patients were enrolled to receive intravenous polymyxin B (1.33–2.53 mg/kg/day), and the median age was 12.5 (range 3.2–17.8) years. Serial plasma samples were collected at steady-state and modelled by population PK analysis. Clinical efficacy and nephrotoxicity of polymyxin B treatment were also assessed. Results PK data were adequately described by a two-compartment model with first-order elimination, and weight was a significant covariate of polymyxin B clearance. Clinical success occurred in 14 of 19 patients (73.7%) and only one patient developed acute kidney injury. The 28 day mortality was 10.5% (2/19). The steady-state polymyxin B exposure was 36.97 ± 9.84 mg·h/L, lower than the therapeutic exposure of 50–100 mg·h/L. With the AUC24h/MIC target of 50, the dosage of 1.5–3.0 mg/kg/day had a probability of target attainments over 90% when MICs were Conclusions Dose adjustment of polymyxin B needs to consider the MIC of infecting pathogens. Current polymyxin B dosing for paediatric patients may be acceptable when MICs are

Background: Along with the medical team, clinical pharmacists played a significant role during the public health emergency of COVID-19. However, to our knowledge, few studies on their work experience with combating COVID-19 have been published. Interviews with clinical pharmacists was conducted to better understand their roles. Through these interviews, further insight would be gained regarding the existing problems within pharmaceutical departments in medical institutions. This information could be used to amend emergency plans for when these departments encounter catastrophic public health events. Methods: A qualitative study design was employed with face-to-face and audio-recorded interviews being conducted with 13 clinical pharmacists. This group included nutritional pharmacists from two hospitals that were fighting against COVID-19 in Henan. All interviews were transcribed verbatim, and the interview data were analyzed thematically using Colaizzi software (version 11). Results: The results contributed to a deeper understanding of the clinical pharmacists’ work experiences providing consultation for the medical department. Four themes emerged from interview data, including the role played by clinical pharmacists, experiences encountered by clinical pharmacists, psychological feelings of clinical pharmacists, and career expectations of clinical pharmacists. Conclusions: This exploratory study provides preliminary evidence that some of the work experiences of clinical pharmacists were aligned. However, some deficiencies, such as lack of participation, were highlighted by the clinical pharmacists and these deficiencies are areas that need to be improved by the department of pharmacy.

This article summarizes and analyzes the clinical features and gene mutation characteristics of children with noncompaction of the ventricular myocardium (NVM). For the 6 children with NVM (4 boys and 2 girls), the age of onset ranged from 3 months to 12 years. Of the 6 children, 5 had arrhythmia, 3 had cardiac insufficiency, 1 had poor mental state, and 1 had chest distress and sighing. NVM-related gene mutations were detected in 4 children, among whom 2 had MYH7 gene mutation, 1 had PRDM16 gene mutation, and 1 had mutations in the ACTN2 and TNNT2 genes. Four children had improvement in cardiac function. The two children with no significant improvement in cardiac function had a younger age of onset, a greater reduction in systolic function on echocardiography, and greater increases in myocardial enzyme and N-terminal pro-brain natriuretic peptide. It is concluded that for children with the initial symptoms of chest distress, sighing, arrhythmia, enlarged heart shadow, and increased myocardial enzyme, echocardiography and cardiac magnetic resonance are recommended for the diagnosis of NVM. NVM can have various genetic mutations.

Background Treatment of recurrent retinal detachment (re-RD) following vitrectomy (post-gas/air tamponade and post-silicone oil removal) is challenging. Previously reported treatment is commonly revision pars plana vitrectomy (PPV) combined with tamponade, which is invasive and a burden both economically and emotionally when compared with scleral buckling (SB). The purpose of this study is to report anatomical and functional outcomes of SB with or without gas tamponade in eyes with recurrent retinal detachment (re-RD) that previously underwent PPV at least once. Methods We retrospectively reviewed the medical records of 14 patients (14 eyes) who underwent PPV at least once and were treated with SB after re-RD. Preoperative characteristics, intraoperative complications, and postoperative data were assessed. The final anatomical and functional outcomes were analyzed. Results The original PPV was performed for primary rhegmatogenous retinal detachment in 11 eyes, macular hole retinal detachment in 2 eyes, and myopic foveoschisis in 1 eye. Previously, 3 eyes underwent one PPV with gas tamponade, and the remaining 11 (79%) eyes underwent 2–5 operations. Seven eyes underwent the procedure with gas injection. At the last follow-up, 13 eyes achieved total retinal attachment and 1 eye had re-RD. The postoperative intraocular pressure was within the normal range, except in 1 eye (6 mmHg). The finest postoperative best-corrected visual acuity (BCVA) was 20/25. There was a significant improvement in BCVA from 20/160 ± 20/63 at baseline to 20/80 ± 20/50 at the last visit in the 13 successfully treated eyes (P = 0.025). Conclusions SB can be effective for re-RD after PPV in specific cases.

Introduction: Cancer causes thousands of deaths worldwide each year. Therefore, monitoring of health status and the early diagnosis of cancer using noninvasive assays, such as the analysis of molecular biomarkers in urine, is essential. However, effective biomarkers for early diagnosis of cancer have not been established in many types of cancer.Areas covered: In this review, we discuss recent findings with regard to the use of urine composition as a biomarker in eleven types of cancer. We also highlight the use of urine biomarkers for improving early diagnosis.Expert opinion: Urinary biomarkers have been applied for clinical application of early diagnosis. The main limitation is a lack of integrated approaches for identification of new biomarkers in most cancer. The utilization of urinary biomarker detection will be promoted by improved detection methods and new data from different types of cancers. With the development of precision medicine, urinary biomarkers will play an increasingly important clinical role. Future early diagnosis would benefit from changes in the utilization of urinary biomarkers.

Previous studies have demonstrated that miRNAs play an important role in tumor development and progression. The role of miR-320d has been studied in several cancers except for glioma. The aim of the study was to investigate the expression levels, biological function, and mechanism of miR-320d in glioma. The expression levels of miR-320d were detected in glioma tissues and cell lines (U87 and U251) by RT-qPCR. Cell proliferation, colony formation, apoptosis, cell cycle, and transwell assays were performed in glioma cell lines transfected with miR-320d mimics or controls to evaluate the effects of miR-320d in vitro. The expression levels of invasive-related proteins were determined by Western blot analysis. Results showed that the expression of miR-320d was significantly decreased in glioma tissues and cell lines. Overexpression of miR-320d could significantly suppress cell growth, migration and invasion, and induced cell apoptosis as well as cell cycle at G0/G1 arrest in U87 and U251 cell lines. Additionally, expression levels of MMP-2, MMP-9, N-cadherin, and integrin-β1 reduced, while E-cadherin increased in miR-320d mimic group. Overall, this study is the first to demonstrate that miR-320d may serve as an independent prognostic factor, indicating that miR-320d is a biomarker for prognosis and therapy in glioma.

The incorporation of the heterocycles into the steroid nucleus has been recognized as a useful strategy to develop new steroidal agents for disease treatment. Representative examples are abiraterone and galeterone, which are presently used in clinic for the treatment of advanced prostate cancers. Herein we have developed the first Al2O3/KF-promoted pfitzinger reactions for the synthesis of new steroidal quinolines. These new steroidal quinolines showed moderate to good antiproliferative activity against several human lung cancer cells. Of these compounds, compound 2f exhibited the best potency toward the tested three lung cancer cells with IC50 values

// Lin-Sen Yang 1, * , Xiao-Jian Zhang 2, * , Yin-Yin Xie 1 , Xiao-Jian Sun 1 , Ren Zhao 2 , Qiu-Hua Huang 1 1 State Key Laboratory of Medical Genomics, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 2 Department of General Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China * These authors have contributed equally to this work Correspondence to: Ren Zhao, email: zhaoren-ruijin@hotmail.com Qiu-Hua Huang, email: hqh10632@rjh.com.cn Keywords: MAFB, SUMOylation, cell cycle, CDK6, colorectal cancer Received: July 28, 2016 Accepted: October 19, 2016 Published: November 05, 2016 ABSTRACT The transcription factor, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), promotes tumorigenesis in some cancers. In this study, we found that MAFB levels were increased in clinical colorectal cancer (CRC) samples, and higher expression correlated with more advanced TNM stage. We identified MAFB amplifications in a majority of tumor types in an assessment of The Cancer Genome Atlas database. Altered MAFB levels due to gene amplification, deletion, mutation, or transcription upregulation occurred in 9% of CRC cases within the database. shRNA knockdown experiments demonstrated that MAFB deficiency blocked CRC cell proliferation by arresting the cell cycle at G0/G1 phase in vitro . We found that MAFB could be SUMOylated by SUMO1 at lysine 32, and this modification was critical for cell cycle regulation by MAFB in CRC cells. SUMOylated MAFB directly regulated cyclin-dependent kinase 6 transcription by binding to its promoter. MAFB knockdown CRC cell xenograft tumors in mice grew more slowly than controls, and wild-type MAFB-overexpressing tumors grew more quickly than tumors overexpressing MAFB mutated at lysine 32. These data suggest that SUMOylated MAFB promotes CRC tumorigenesis through cell cycle regulation. MAFB and its SUMOylation process may serve as novel therapeutic targets for CRC treatment.

Purpose Polyphyllin VI, a main active saponin isolated from traditional medicinal plant Paris polyphylla, has exhibited antitumor activities in several cancer cell lines. In the present study, we investigated the antitumor effect of Polyphyllin VI against human osteosarcoma cells (U2OS) and the underlying molecular mechanisms. Methods The U2OS cell lines were used to determine the antiproliferative effect of Polyphyllin VI by CCK8 assay. Cell cycle was analyzed by flow cytometry. The Polyphyllin VI-induced apoptosis was determined by Annexin V-APC/7-AAD apoptosis detection kit and JC-1 staining. Meanwhile, the autophagy was determined by acridine orange staining. The apoptosis and autophagy-related proteins were monitored by Western blot assay. Subsequently, intracellular hydrogen peroxide (H2O2) and the activation of ROS/JNK pathway were detected. Results Polyphyllin VI could potently inhibit cell proliferation by causing G2/M phase arrest. Polyphyllin VI induced mitochondria-mediated apoptosis with the upregulation of proapoptotic proteins Bax and poly ADP-ribose polymerase, and downregulation of antiapoptotic protein Bcl-2 in U2OS cells. Concomitantly, Polyphyllin VI provoked autophagy with the upregulation of critical Atg proteins and accumulation of LC3B-II. Intracellular H2O2 production was triggered upon exposure to Polyphyllin VI, which could be blocked by ROS scavenger. Polyphyllin VI dramatically promoted JNK phosphorylation, whereas it decreased the levels of phospho-p38 and ERK. Conclusion Our results reveal that Polyphyllin VI may effectively induce apoptosis and autophagy to suppress cell growth via ROS/JNK activation in U2OS cells, suggesting that Polyphyllin VI is a potential drug candidate for the treatment of osteosarcomas.

Leukemia inhibitory factor receptor (LIFR) has been documented as a cancer promoter and to be present at high levels in various types of tumor tissues. In our search for molecules prognostic of colorectal cancer (CRC), we found high levels of LIFR in CRC tissue samples. Further analyses revealed that LIFR was indeed prognostic of CRC patient survival, and was associated with tumor size, lymphatic metastasis and stages. LIFR was found to promote tumor growth, metastasis and angiogenesis both in vitro and in vivo. High levels of LIFR in CRC facilitated proliferation and migration of endothelial cells, resulting in an increase in angiogenic activity. Moreover, interleukin 8 (IL-8) was found to play a role in the LIFR induced angiogenesis. IL-8 levels were correlated with LIFR levels in CRC tissues, whereas depletion of IL-8 led to a reduced angiogenic activity of LIFR in CRC cells. In addition, LIFR increased phosphorylation level of Erk, which regulates il-8 transcription. We conclude that LIFR is possibly a valuable prognostic marker for CRC. Our results also implicate a mechanism by which LIFR regulates tumor angiogenesis through Erk/IL-8 pathway, and that LIFR could be a potential therapeutic target for CRC.

It has been proven that carbon nanoparticles or diesel exhaust particles stimulate platelet activation. However, the effect of fine particle matter (PMPMThe filed-emission scanning electron microscope scanning showed that PMPM

The objective of this study was to evaluate the gestational results obtained with vitrified-thawed human cleavage-stage embryo by two different thaw protocols. Embryo development was observed to cleavage-stage and embryos were cryopreserved by vitrification on day 3 after oocyte retrieval. 51 cycles were thawed using vitrification warming kit with decreasing concentrations of sucrose in 3 dilutions ( 1.0, 0.5 and 0 mol per L respectively) as group 1, 56 cycles were thawed with decreasing concentrations of sucrose in 5 dilutions ( 0.8, 0.6, 0.33, 0.2 and 0 mol per L respectively) as group 2. Embryo survival (50 percent intact blastomeres), complete embryo survival (100 percent intact blastomeres), pregnancy and implantation rates were compared, and development rates the day after thawing were also compared. Multivariate analysis showed a significant difference in embryo immediate morphological survival rate, complete survival and clinical pregnancies rate between the two groups respectively (87.0 vs. 98.6 percent, p=0.000; 71.0 vs 82.0 percent embryo subsequent development rates, mean number of transferred embryos was similar between the two groups. (61.4 vs. 61.3 percent, p=0.502; 2.2 +/ 0.5 vs. 2.4 +/- 0.6, p=0.113). In addition, no differences in implantation rate were observed between two groups (17.7 vs. 25.6 percent, P=0.138). No difference in the multiple pregnancy rates was found among the two groups also.

Investigations on diverse aspects of fluoro-organic compounds have rapidly increased during the past decades. Because natural sources of fluoro-organic compounds are extremely rare, the industrial synthesis of fluorinated organic compounds and production of fluorinated natural product derivatives have greatly expanded in recent years because of their increasing importance in the agrochemical and pharmaceutical industries. Due to structural complexity or instability, synthetic modification is often not possible, and various biofluorination strategies have been developed in recent years for applications in the anti-cancer, anti-viral and anti-infection fields. Despite the industrial importance of fluorinated compounds, there have been serious concerns worldwide over the levels and synthetic routes of certain fluorinated organic compounds, in particular perfluorinated chemicals (PFCs). PFCs are emerging and recalcitrant pollutants which are widely distributed in the environment and have been detected in humans and wildlife globally. PFCs have been demonstrated to be potentially carcinogenic, adversely affect the neuroendocrine and immune systems, and produce neurotoxicity, heptatotoxicity and endocrine disrupting effects in vertebrate animals. Here, we provide an overview of recent advances in our understanding of the biology of various fluoro-organic compounds and perspectives for new enzymes and metabolic pathways for bioremediation of these chemicals.

Of 122 consecutive procedures, 31 were not assisted hatching (AH), which served as the control group, 34 were AH with 40 microm thinning of the zona, and 57 were AH with 80 microns of the zona thinning. The pregnancy and implantation rates were significantly higher in 80 microns thinning group compared to control group (40.3 vs. 16.1 percent, P=0.03; 21.5 vs. 7.5 percent, P=0.007, respectively). In addition, the implantation rate was signigicantly higher in 80 microns group than in 40 microns group (21.5 percent vs.9.4 percent, P=0.024). The results indicated that the size of the zona pellucida thinning by laser may influence the pregnancy and implantation rates following frozen-thawed cleaved embryo transfer.

Background and purpose To investigate the feasibility and effectiveness of utilizing active breathing coordinator (ABC) in 3DCRT for HCC. Materials and methods A dosimetric comparison between the free-breathing (FB) plan and ABC plan in HCC 3DCRT was performed. Set-up errors and reproducibility of diaphragm position using ABC were measured, and patients’ acceptance was also recorded. Results From April 2005 to February 2007, 28 HCC were irradiated with ABC and they tolerated ABC well. The mean dose to normal liver was reduced from 16.9 Gy in FB plan to 14.3 Gy in ABC plan. PTV for ABC and FB plans were 529 cm3 and 781 cm3, respectively, and V23 were reduced from 45% to 30%. The predicted incidences of radiation-induced liver disease by Lyman model were 1% and 2.5%, respectively, in favor of ABC plan. The systematic and random errors for the ABC and FB plans were 1.2 mm vs. 4.7 mm, 1.6 mm vs. 3.5 mm, and 1.8 mm vs. 2.7 mm, respectively, in cranio-caudal, anterior-posterior, and left-right directions. The average intrafraction reproducibility of diaphragm position in cranio-caudal direction was 1.6 mm, and the interfraction, 6.7 mm. Conclusions The utilization of ABC in HCC 3DCRT is feasible, and can reduce liver irradiation.

To evaluate the response and tolerance in hepatocellular carcinoma (HCC) patients treated by three-dimensional conformal radiotherapy (3DCRT) combined with. transcatheter arterial chemoembolization (TACE).Fourty-six HCC patients confirmed by cytology or histology were studied. All patients underwent TACE 1 to 3 courses. Then they received 3DCRT after an interval of about one month. 3DCRT was given with the field covering the tumor with a generous margin. 6 MV X-ray was used. The total dose was 30 - 54 Gy, in daily 2 Gy fractions. Immediate response was recorded according to the WHO criteria carried out by serial CT scan one month after 3DCRT. Irradiation toxicities were scored by the RTOG criteria. Acute liver toxicity was graded according to the common toxicity criteria (CTC) of National Cancer Institute. Late toxicity was focused on radiation-induced liver disease (RILD).Partial response was observed in 8 (17.4%) patients. Stable disease and progressive disease was observed in 35 (76.1%) patients and 3 (6.5%) patients, respectively. No complete response was observed at the time of the response evaluation. The overall survival rate at 1-, 2- and 3-year was 60.9%, 39.1% and 28.3%, respectively, with a median survival period of 16 months. The 1-, 2- and 3-year local progression-free rate was 73.9%, 56.5% and 39.1%, respectively. The 1-, 2- and 3-year distant metastasis rate was 15.2%, 21.7% and 34.8%. Univariate analysis showed that favorable prognostic predictors for survival were: T3 stage, CACA 2001 stage I, absence of portal thrombosis, Child-Pugh grade A and irradiation dose of45 Gy. Irradiation dose and liver cirrhosis were identified by Cox-regression analysis as independent predictors for survival. Two patients experienced CTC grade 1 acute hepatic toxicity and three patients experienced grade 3 acute hepatic toxicity. Two patients developed RILD. Three patients experienced RTOG grade 1 acute gastrointestinal complication and one patient experienced acute gastrointestinal bleeding. Five patients experienced RTOG grade 1 leucopenia, and five patients experienced grade 2 leucopenia.3DCRT combined with TACE is safe and effective for HCC. It is worthy of a further dose escalation study.

Since haloacetic acids (HAAs), which are nonvolatile and of high carcinogenic risk, are common species of chlorinated disinfection by-products(DBPs) in drinking water, and little has been known in China, it is necessary to make a survey about the kinds and levels of HAAs in drinking water of the nation.HAAs were analyzed using gas chromatography with electron capture detector(GC/ECD) and relatively complex pretreatment process of sample was applied. Five main cities in different areas of China were chosen in the survey.Studies showed that the main species of HAAs in drinking water in China were DCAA and TCAA, ranging from 0.4 microg/L to 12.85 microg/L and from 0.56 microg/L to 10.98 microg/L, respectively. MBAA and DBAA were also detected in one city, ranging from 2.20 microg/L to 4.95 microg/L and 1.10 microg/L to 2.81 microg/L, respectively. Therefore, the contents of HAAs varied, usually no more than 25 microg/L. Based on the acquired data to date, it is known that the concentrations of HAAs in drinking water in China were surely under the limits of Sanitary Standard for Drinking Water Quality (China, 2001).A wider survey of HAAs in drinking water should be conducted throughout the nation to get adequate data and information, the ultimate aim of which is to control HAAs pollution and keep the balance between microbiological safety insurance and chemical risk control, minimize the formation of DBPs and ensure the safety of water supply at the same time.