Pd-Catalyzed Tandem Cyclization via C–H Arylation and Acylation for the Construction of Polycyclic Scaffolds

The first Pd-catalyzed tandem cyclization of imidazo­[1,2-<i>a</i>]­pyridines with 2-chlorobenz­aldehydes through C–H arylation and acylation is presented for the efficient synthesis of novel 6<i>H</i>-benzo­[<i>b</i>]­imidazo­[5,1,2-<i>de</i>]­quinolizin-6-ones. The direct acylation reaction proceeded smoothly without the aid of directing groups and in the presence of air as a clean and free terminal oxidant

Table_1_Determination of the effective dose of dexmedetomidine to achieve loss of consciousness during anesthesia induction.DOCX

BackgroundDexmedetomidine (DEX) is a sedative with greater preservation of cognitive function, reduced respiratory depression, and improved patient arousability. This study was designed to investigate the performance of DEX during anesthesia induction and to establish an effective DEX induction strategy, which could be valuable for multiple clinical conditions.MethodsPatients undergoing abdominal surgery were involved in this dose-finding trial. Dixon's up-and-down sequential method was employed to determine the effective dose of DEX to achieve the state of “loss of consciousness”, and an effective induction strategy was established with continuous infusion of DEX and remifentanil. The effects of DEX on hemodynamics, respiratory state, EEG, and anesthetic depth were monitored and analyzed.ResultsThrough the strategy mentioned, the depth of surgical anesthesia was successfully achieved by DEX-led anesthesia induction. The ED50 and ED95 of the initial infusion rate of DEX were 0.115 and 0.200 μg/kg/min, respectively, and the mean induction time was 18.3 min. The ED50 and ED95 of DEX to achieve the state of “loss of consciousness” were 2.899 (95% CI: 2.703–3.115) and 5.001 (95% CI: 4.544–5.700) μg/kg, respectively. The mean PSI on the loss of consciousness was 42.8 among the patients. During anesthesia induction, the hemodynamics including BP and HR were stable, and the EEG monitor showed decreased α and β powers and increased θ and δ in the frontal and pre-frontal cortices of the brain.ConclusionThis study indicated that continuous infusion of combined DEX and remifentanil could be an effective strategy for anesthesia induction. The EEG during the induction was similar to the physiological sleep process.</p

Univariate Cox regression analysis of all patients (n = 68).

*<p>The tumor grade and size are only applied to the primary tumors.</p

Univariate Cox regression analysis of patients in the testing cohort (n = 40).

*<p>Five patients’ UISS risk scores were not available (n = 35).</p

Kaplan-Meier analysis of cancer-specific survival in clear cell renal cell carcinoma (ccRCC) patients.

<p>They are all the testing cohort patients who are stratified by the 4-miRNA signature using microarray (n = 40) (A) and quantitative PCR (qPCR) (n = 40) (B), and by the UCLA Integrated Staging System (UISS) (n = 35) (C). (low: low risk group; high: high risk group; intermediate: intermediate risk group.).</p

Relative odds for patients with metastasis associated with the risk core, patient’s age and sex, tumor grade and size, and clinical stage in the testing cohort (n = 40).

*<p>Met: patient with concurrent and subsequent metastasis; Non-met: patient without metastasis.</p>**<p>Exact logistic regression is used due to o count in stage IV nom-met patients.</p

Differentially expressed miRNAs in metastatic clear cell renal cell carcinoma compared to localized tumor (n = 28).

<p>Differentially expressed miRNAs in metastatic clear cell renal cell carcinoma compared to localized tumor (n = 28).</p

Differentially expressed miRNAs in clear cell renal cell carcinoma compared to benign kidney tissue (n = 38).

<p>Tumor: clear cell renal cell carcinoma.</p

ROC curve of miRNA risk scores using microarray training data set.

<p>The red dot indicates the selected score cutoff of −8.12, which achieves the highest true positive rate (100%) and lowest false positive rate (8%).</p

Clinical characteristics of patients and tumor specimens (n = 68) in the training and testing cohorts.

*<p>The tumor grade and size are only applied to the primary tumors (n = 53).</p