The Sedative Effects of Inhaled Nebulized Dexmedetomidine on Children: A Systematic Review and Meta-Analysis.

Background: Children that need surgery and medical examinations are often uncooperative, and preoperative sedation is necessary. We aimed to assess the safety and efficacy of inhaled nebulized dexmedetomidine in children for sedation that underwent medical examinations or surgery. Methods: We systematically searched PubMed, Web of science, Embase, and Cochrane library, for randomized controlled trials of Intranasal dexmedetomidine using a spray or a mucosal atomization device in children undergoing examination or elective surgery. We included all studies that analyzed the sedation efficiency of intranasal dexmedetomidine in children. Results: Ten studies with 1,233pediatric patients were included. Compared to other sedation treatments, inhaled nebulized dexmedetomidine showed similar sedation satisfaction [risk ratio RR: 1.02; 95% confidence interval (CI): 0.87-1.18; P = 0.83; I2 = 72%]. there was also no statistical difference in the success rate of separation from parents (RR: 0.96; 95% CI: 0.82-1.12; P = 0.58; I2 = 67%), and mask acceptability (RR: 1; 95% CI: 0.83-1.20; P = 0.99; I2 = 35%). But it is worth mentioning that nebulized dexmedetomidine combined with ketamine provided better sedation satisfaction (RR: 0.69; 95% CI: 0.49-0.96; I2 = 49%) and more satisfactory separation from parents (RR: 0.85; 95% CI: 0.74-0.97; I2 = 0%). Moreover, nebulized dexmedetomidine reduced the occurrences of nausea and vomiting (RR: 0.28; 95% CI: 0.15-0.51; P < 0.01; I2 = 10%) and emergence agitation (RR: 0.30; 95% CI: 0.18-0.49; P < 0.01; I2 = 0%). There are no hypotension or arrhythmia reported that required intervention in all articles. Conclusion: Compared to other premedication treatments, inhaled nebulized dexmedetomidine provided equivalent sedation satisfaction for the examination or preoperative sedation of children, but it reduced the occurrences of emergence agitation and postoperative nausea and vomiting.

Influenza-existing drugs and treatment prospects.

Influenza is a century-old disease that continues to baffle humans by its frequently changing nature, seasonal epidemics, and occasional pandemics. Approximately 9% of the world's population is infected by the influenza virus annually. The emergence of novel strains because of rapid mutations as well as interspecies disease contamination, limits the efficiency of strain-specific vaccines. Anti-influenza drugs such as neuraminidase inhibitors, M2 ion channel inhibitors, etc. have become the first line of defense in prophylaxis and early containment of the disease. But the growing drug resistance due to drug-induced selective pressure has also limited the efficacy of those drugs. Because we can't predict the next strain types, their virulence, or the severity of the next epidemic/pandemic caused by influenza virus, we ought to gear up for the development of novel anti-influenza drugs with a broad spectrum of reactivity against all strains and subtypes, better bioavailability, easier administrative pathways, and lesser adverse effects. Various new compounds with each having significantly different target molecules and pharmacologic activity have shown potential against influenza virus strains in laboratory situations as well as clinical trials. We should also consider combination therapy to boost the efficacy of existing drugs. This review is aiming to succinctly document the recent signs of progress regarding anti-influenza drugs both in the market and under investigation.

Design, synthesis, in vitro and in vivo anti-respiratory syncytial virus (RSV) activity of novel oxizine fused benzimidazole derivatives.

Respiratory syncytial virus (RSV) causes serious lower respiratory tract infections. Currently, the only clinical anti-RSV drug is ribavirin, but ribavirin has serious toxic side effect and can only be used by critically ill patients. A series of benzimidazole derivatives were synthesized starting from 1,4:3,6-dianhydro-d-fructose and a variety of o-phenylenediamines. Evaluation of their antiviral activity showed that compound a27 had the highest antiviral activity with a half maximal effective concentration (EC50) of 9.49 µM. Investigation of the antiviral mechanism of compound a27 indicated that it can inhibit the replication of RSV by inhibiting apoptosis and autophagy pathways. Retinoic acid-inducible gene (RIG)-I, TNF receptor associated factor (TRAF)-3, TANK binding kinase (TBK)-1, interferon regulatory factor (IRF)-3, nuclear factor Kappa-B (NF-κB), interferon (IFN)-ß, Toll-like receptor (TLR)-3, interleukin (IL)-6 were suppressed at the cellular level. Mouse lung tissue was subjected to hematoxylin and eosin (HE) staining and immunohistochemistry, which showed that RSV antigen and M gene expression could be reduced by compound a27. Decreased expression of RIG-I, IRF-3, IFN-ß, TLR-3, IL-6, interleukin (IL)-8, interleukin (IL)-10, inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α was also found in vivo.

Antiviral Activity of 3D, a Butene Lactone Derivative Against Influenza A Virus In Vitro and In Vivo.

Influenza A virus is a highly variable and contagious respiratory pathogen that can cause annual epidemics and it poses an enormous threat to public health. Therefore, there is an urgent need for a new generation of antiviral drugs to combat the emergence of drug-resistant strains of the influenza virus. A novel series of butene lactone derivatives were screened and the compound 3D was selected, as it exhibited in vitro potential antiviral activity against A/Weiss/43 H1N1 virus with low toxicity. In addition, 3D dose-dependently inhibited the viral replication, expression of viral mRNA and viral proteins. 3D exerted a suppressive effect on A/Virginia/ATCC2/2009 H1N1 and A/California/2/2014 H3N2 in vitro. The time-of-addition analysis indicated that 3D suppressed H1N1 in the early stage of its life cycle. A/Weiss/43 H1N1-induced apoptosis in A549 cells was reduced by 3D via the mitochondrial apoptosis pathway. 3D could decrease the production of H1N1-induced pro-inflammatory cytokines that are induced by H1N1 in vitro and in vivo. The administration of 3D reduced lung lesions and virus load in vivo. These results suggest that 3D, which is a butene lactone derivative, is a promising agent for the treatment of influenza A virus infection.

Effects of Sugammadex versus Neostigmine on Intraoperative Coagulation Profiles in Patients with Thyroidectomy.

BACKGROUND: Sugammadex has been a revolutionary reversal of neuromuscular blockade. It is known to be highly efficient. However, a change in the coagulation profile is one of the most dangerous potential complications which is a concern for both surgeon and anesthetist. Bleeding may cause hypovolemic shock, hematoma, and so on. To investigate the effects of sugammadex on coagulation profiles in patients with thyroidectomy, we compared patients that were treated with either sugammadex or neostigmine. PATIENTS AND METHODS: Eighty patients with thyroid neoplasms undergoing thyroidectomy were randomly allocated to sugammadex group (group S) or neostigmine group (group N). Induction of anesthesia was preformed using propofol, sufentanil, and rocuronium. Group S received sugammadex 2.0mg/kg after trachea intubation, similarly Group N received neostigmine 40 µg/kg, for reversal of rocuronium-induced neuromuscular blockade. The intraoperative coagulation profiles were monitored after the rocuronium injection (T0), 10 minutes after reversal (T1) and 30 minutes after reversal (T2) by testing activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), thrombin time (TT), and TEG-Haemonetics. Amount of bleeding was recorded during perioperative period. RESULTS: There was no significant difference in the thromboelastogram, APTT, PT, FIB, or TT measurements at each time point in Group N. The reaction time (R time) and kinetics time (K time) of Group S in T1 were significantly longer than the corresponding times at T0 and T2, and the R times were significantly longer than those in Group N at the same time points (P<0.05). Additionally, in Group S, the APTT was prolonged in T1 and returned to normal in T2. CONCLUSION: The result showed that sugammadex provided transient efficacy in prolonging the coagulation parameters, while neostigmine did not change the coagulation profile.

Screening and pharmacodynamic evaluation of the antirespiratory syncytial virus activity of steroidal pyridine compounds in vitro and in vivo.

Respiratory syncytial virus (RSV) causes serious lower respiratory tract infections and there are currently no safer or more effective drugs available. It is important to find novel medications for RSV infection. A series of steroidal pyridines were synthesized for screening and evaluation of their antiviral activity and investigation of their antiviral mechanism of action. Compound 3l had the highest antiviral activity, with a half-maximal effective concentration (EC50 ) of 3.13 µM. Compound 3l was explored for its effects in vitro on RSV 2 h before infection (pretreatment), at the time of infection (competition), and 2 h after infection (postinfection). Toll-like receptor (TLR)-3, retinoic acid-inducible gene (RIG)-I, interleukin (IL)-6, and interferon (IFN)-ß were suppressed at the cellular level. Mouse lung tissue was subjected to hematoxylin and eosin (HE) staining and immunohistochemistry, which showed that RSV antigen and M gene expression could be reduced by compound 3l. Decreased expression of TLR-3, RIG-I, IL-6, IFN-ß, and IL-10 was also found in vivo. The results indicated that compound 3l exerted its antiviral effects mainly through inhibition of viral replication and downregulation of inflammatory factors.

Serum Trefoil Factor 3 as a Protein Biomarker for the Diagnosis of Colorectal Cancer.

Colorectal cancer is one of the most frequent causes of cancer-related deaths worldwide. Thus, there is a need for timely diagnosis and effective treatment. Our aim in the present study was to detect the serum level of trefoil factor 3 protein and evaluate the diagnostic accuracy of trefoil factor 3 in patients with colorectal cancer. We collected serum samples from 204 participants (127 patients with colorectal cancer, 35 patients with polyps, and 42 healthy controls). The levels of serum trefoil factor 3 and carcinoembryonic antigen expression were measured by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were plotted to calculate the diagnostic accuracy of trefoil factor 3 in patients with colorectal cancer. The serum levels of trefoil factor 3 in patients with colorectal cancer (6.66 ± 2.4 ng/mL; P < .00l) and polyps (3.86 ± 1.3 ng/mL; P < .00l) were significantly increased compared to healthy controls (2.09 ± 1.0 ng/mL). Moreover, the area under the receiver operating characteristic curve for trefoil factor 3 was greater than carcinoembryonic antigen (0.889 vs 0.715). At a cutoff value of 5.591 ng/mL, the diagnostic sensitivity, specificity, and likelihood ratio of serum trefoil factor 3 for colorectal cancer was 74.2%, 94.8%, and 14.25, respectively. Furthermore, the serum trefoil factor 3 levels in early colorectal cancer (TNM stage I, 3.67 ± 1.27 ng/mL) were significantly increased compared to healthy controls ( P < .001); however, there was no significant difference compared to patients with polyps ( P = .576). We observed that the serum trefoil factor 3 levels decreased after surgery (6.66 ± 2.4 vs 4.48 ± 1.80 ng/mL; P < .001). In addition, high serum trefoil factor 3 levels were associated with poor tumor differentiation and clinical TNM stage ( P < .05). In conclusion, serum trefoil factor 3 is a promising biomarker for the diagnosis of colorectal cancer and prognosis of patients.

Effects of propofol versus sevoflurane on cerebral oxygenation and cognitive outcome in patients with impaired cerebral oxygenation.

BACKGROUND: Postoperative neurocognitive dysfunction induced by anesthetics, particularly in elderly patients with impaired oxygenation, is a common complication of surgery and is eliciting increased interest in clinical practice. To investigate the effects of anesthetics on neurocognition, we compared the effects of propofol versus sevoflurane on cerebral oxygenation and cognitive outcome in patients with impaired cerebral oxygenation undergoing general anesthesia. METHODS: Sixty-three patients with impaired cerebral oxygenation (jugular venous bulb oxygen saturation [SjvO2] <50%) or cerebral blood flow/cerebral metabolic rate of oxygen ([CBF/CMRO2] ≤15%) undergoing elective abdominal surgery were randomly allocated into propofol group (group P) or sevoflurane group (group S). The clinical parameters and jugular venous bulb blood gas analysis were monitored throughout the surgical procedure. Cognitive function was assessed with the mini-mental state examination and Montreal Cognitive Assessment at day 1 and day 7 following surgery. S100ß protein in plasma was measured using enzyme-linked immunosorbent assay. RESULTS: The SjvO2 increased during anesthesia induction and surgery when compared to baseline but had no significant difference between group P and group S. When compared to baseline, the CBF/CMRO2 was increased only at the end of surgery and extubation in group P; however, the CBF/CMRO2 in group S was increased during anesthesia induction at 1 hour, 2 hours, end of surgery, and extubation. Furthermore, the CBF/CMRO2 in group S was significantly higher than that in group P during anesthesia induction at 1 hour, 2 hours, and end of surgery. S100ß protein did not significantly change at extubation and 1 day after surgery in both groups when compared to baseline. There was no significant difference in mini-mental state examination and Montreal Cognitive Assessment scores between group P and group S at all time points. CONCLUSION: Sevoflurane showed similar effects in postoperative neurocognitive function as propofol but could improve cerebral oxygenation in patients with impaired cerebral oxygenation.

Role of PKC-ERK signaling in tamoxifen-induced apoptosis and tamoxifen resistance in human breast cancer cells.

This study was designed to investigate the role of protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in tamoxifen (TAM)-induced apoptosis and drug resistance in human breast cancer cells. Drug-sensitive, or estrogen receptor (ER)-positive human breast carcinoma cells (MCF-7) and the multi-drug-resistant variant (ER-negative) MCF-7/ADR cells were treated with doses of TAM for various periods of time. Cell viability and apoptosis were assessed using cell counting, DNA fragmentation and flow cytometric analysis. We found that TAM administration caused a significant increase in apoptosis of MCF-7 cells but not MCF-7/ADR cells. Western blot analysis revealed enhanced expression of PKCδ but decreased expression of PKCα in ER-positive MCF-7 cells; while ER-negative MCF-7/ADR cells had decreased levels of PKCδ and increased levels of PKCα. Interestingly, we observed that in MCF-7 cells, TAM stimulated apoptosis by promoting rapid activation of PKCδ, antagonizing downstream signaling of ERK phosphorylation; while in MCF-7/ADR cells, TAM upregulated PKCα, which promoted ERK phosphorylation. These results suggest that PKCδ enhances apoptosis in TAM-treated MCF-7 cells by antagonizing ERK phosphorylation; while the PKCα pathway plays an important role in TAM-induced drug resistance by activating ERK signaling in MCF-7/ADR cells. The combination of TAM with PKCα and ERK inhibitors could promote TAM-induced apoptosis in breast cancer cells.

Resveratrol affects protein kinase C activity and promotes apoptosis in human colon carcinoma cells.

BACKGROUND: Resveratrol has been reported to have potential chemopreventive and apoptosis-inducing properties in a variety of tumor cell lines. OBJECTIVE: In this study, to investigate the effects of resveratrol on protein kinase C (PKC) activity and apoptosis in human colon carcinoma cells, we used HT-29 cells and examined the PKCα and ERK1/2 signaling pathways. METHODS: To test the effects of resveratrol on the growth of HT- 29 cells, the cells were exposed to varying concentrations and assessed with the the MTT cell-viability assay. Fluorescence-activated cell sorter (FACS) analysis was applied to determine the effects of resveratrol on cell apoptosis. Western blotting was performed to determine the protein levels of PKCα and ERK1/2. In inhibition experiments, HT-29 cells were treated with Go?6976 or PD98059 for 30 min, followed by exposure to 200 µM resveratrol for 72 h. RESULTS: Resveratrol had a significant inhibitory effect on HT-29 cell growth. FACS revealed that resveratrol induced apoptosis. Western blotting showed that e phosphorylation of PKCα and ERK1/2 was significantly increased in response to resveratrol treatment. Pre-treatment with PKCα and ERK1/2 inhibitors (Go?6976 and PD98059) promoted apoptosis. CONCLUSION: Resveratrol has significant anti-proliferative effects on the colon cancer cell line HT-29. The PKC- ERK1/2 signaling pathway can partially mediate resveratrol-induced apoptosis of HT-29 cells.

Trigeminal nerve and facial nerve palsy after combined spinal-epidural anesthesia for cesarean section.

A case of emergency cesarean section due to a prolonged second stage of labor in a 29 year-old woman is presented. She had trigeminal nerve and facial nerve palsy after combined spinal-epidural anesthesia for cesarean section.

Cystatin C and serum creatinine in estimating acute kidney injury of shock patients.

BACKGROUND: Serum creatinine (SCr) is the most commonly used parameter to estimate renal function impairement, but there are some shortcomings. Many factors including age, gender, drug, diet, muscle mass and metabolic rate can influence SCr, leading to an inaccurate estimation of kidney impairment. Studies have shown that cystatin C (CysC) is not affected by factors such as muscle mass, age, gender, diet, inflammation or tumor. The present study was undertaken to compare the sensitivity of CysC and SCr in evaluating renal function impairment at early stage of shock. METHODS: Seventy-one patients aged 38.3±21.4 years, who had been treated at the Emergency Medicine Department of the First Affiliated Hospital, Sun Yat-sen University between February 2006 and June 2007, were studied. They were divided into groups A, B, C, and D according to the shock time. Serum sample was drawn from each patient at 1, 2, 3, 4 hours after shock to determine SCr and CysC. CysC and SCr were determined again at 72 hours and 7 days after shock. RESULTS: CysC increased earlier than SCr in the 71 patients, and CysC decreased slower than SCr when shock was corrected. CysC increased at 1 hour after shock. There was a negative correlationship between CysC, SCr and glomerular filtration rate (GFR), especially at early stage of shock. CONCLUSIONS: There is renal injury at early stage of shock. CysC is more sensitive than SCr in assessing renal function at the early stage of shock.

ShRNA-mediated gene silencing of beta-catenin inhibits growth of human colon cancer cells.

AIM: To observe the gene silencing mediated by the specific shRNA targeted against beta-catenin and its effect on cell proliferation and cycle distribution in the human colon cancer cell line Colo205. METHODS: Two shRNA plasmid vectors against beta-catenin were constructed and transfected into Colo205 cells with Lipofectamine2000. The down-regulations of beta-catenin, c-myc and cyclinD1 expressions were detected by RT-PCR and western blot analysis. The cell proliferation inhibitions were determined by MTT assay and soft agar colony formation assay. The effect of these two beta-catenin shRNAs on cell cycle distribution and apoptosis was examined by flow cytometry. RESULTS: These two shRNA vectors targeted against beta-catenin efficiently suppressed the expression of beta-catenin and its down stream genes, c-myc and cyclinD1. The expression inhibition rates were around 40%-50% either at the mRNA or at the protein level. The shRNA-mediated gene silencing of beta-catenin resulted in significant inhibition of cell growth both on the culture plates and in the soft agar. Moreover, the cancer cells showed significant G0/G1 arrest and increased apoptosis at 72 h post transfection due to gene silencing. CONCLUSION: These specific shRNAs targeted against beta-catenin could have a gene silencing effect and block the WNT signaling pathway. They could inhibit cell growth, increase apoptosis, and induce cell cycle arrest in Colo205 cells. ShRNA interference against beta-catenin is of potential value in gene therapy of colon cancer.