Kinetically controlled synthesis of rotaxane geometric isomers.

Geometric isomerism in mechanically interlocked systems-which arises when the axle of a mechanically interlocked molecule is oriented, and the macrocyclic component is facially dissymmetric-can provide enhanced functionality for directional transport and polymerization catalysis. We now introduce a kinetically controlled strategy to control geometric isomerism in [2]rotaxanes. Our synthesis provides the major geometric isomer with high selectivity, broadening synthetic access to such interlocked structures. Starting from a readily accessible [2]rotaxane with a symmetrical axle, one of the two stoppers is activated selectively for stopper exchange by the substituents on the ring component. High selectivities are achieved in these reactions, based on coupling the selective formation reactions leading to the major products with inversely selective depletion reactions for the minor products. Specifically, in our reaction system, the desired (major) product forms faster in the first step, while the undesired (minor) product subsequently reacts away faster in the second step. Quantitative 1H NMR data, fit to a detailed kinetic model, demonstrates that this effect (which is conceptually closely related to minor enantiomer recycling and related processes) can significantly improve the intrinsic selectivity of the reactions. Our results serve as proof of principle for how multiple selective reaction steps can work together to enhance the stereoselectivity of synthetic processes forming complex mechanically interlocked molecules.

Observer's Assessment of Alertness/Sedation-based titration reduces propofol consumption and incidence of hypotension during general anesthesia induction: A randomized controlled trial.

Administration of a single propofol bolus dose for anesthesia induction causes hypotension. We included 160 patients (74 males and 86 females; mean age, 42.4 ± 10.7 [range: 18-60] years) with the American Society of Anesthesiologists status I-II undergoing elective surgery under general anesthesia. Using simple randomization, the patients were divided into a conventional group (n = 80; received 2 mg/kg propofol at a rate of 250 mg/min) and titrated group (n = 80; received propofol at a rate of 1 mg/kg/min until the Observer's Assessment of Alertness/Sedation scale score reached 1 point). Fentanyl (4 µg/kg) and cisatracurium (0.2 mg/kg) were administered, as appropriate. Systolic blood pressure, diastolic blood pressure, mean blood pressure, and heart rate were recorded at different time points. Propofol consumption, hypotension, and other adverse events were recorded. All the patients were intubated without awareness. Compared with the conventional group, the titrated group showed more stable blood pressure (p < 0.05), as well as a lower decrease in systolic blood pressure, mean blood pressure at 1 and 3 min, and diastolic blood pressure at 1 min after propofol administration (p < 0.01). Moreover, compared with the conventional group, the titrated group showed a lower post-intubation hypotension incidence (9 vs. 19 cases; p = 0.04), as well as lower total propofol dosage and propofol dose per kilogram of body weight (93.57 ± 14.40 mg vs. 116.80 ± 22.37 mg and 1.73 ± 0.27 mg/kg vs. 2.02 ± 0.08 mg/kg, respectively, p < 0.01). Compared with conventional propofol usage, titrated propofol administration can reduce the incidence of hypotension and propofol consumption during anesthesia induction.

Radiofrequency versus microwave ablation for hepatocellular carcinoma within the Milan criteria in challenging locations: a retrospective controlled study.

PURPOSE: The aim of this study was to compare the safety and efficacy of radiofrequency ablation (RFA) with microwave ablation (MWA) for hepatocellular carcinoma (HCC) within the Milan criteria in challenging locations. METHODS: This study retrospectively investigated 201 consecutive patients with Milan criteria HCCs who underwent RFA (RFA group, n = 150) or MWA (MWA group, n = 51) between January 2012 and December 2016. Overall survival (OS), recurrence-free survival (RFS), local tumor control, and treatment-related complications were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model. RESULTS: Median follow-up duration was 36.7 months (range: 6.2-64.0 months). Cumulative 1-, 3-, and 5-year OS rates were 97.9%, 92.3%, and 80.6% in the MWA group and 96.4%, 87.4%, and 78.2% in the RFA group, respectively, (P = 0.450). Cumulative RFS rates at 1, 3, and 5 years were 93.2%, 74.4%, and 63.7% in the MWA group and 80.3%, 57.3%, and 49.6% in the RFA group, respectively, (P = 0.097). Multivariate analyses showed that variable categories "patient age above 65 years" (P = 0.004) and "more than one tumor" (P = 0.004) were associated with overall mortality, and "patient age above 65 years" (P = 0.048) and "tumor size greater than 3 cm" (P = 0.009) were associated with inferior RFS. The incidences of major complications were not significantly different between the two groups (3.3% vs 3.9%, P = 0.843). CONCLUSIONS: RFA and MWA were associated with comparable safety and efficacy for HCC within the Milan criteria in challenging locations. Further study in a large, multi-center patient cohort is necessary to validate the results.

[Effects of propofol sedation on psychological stress in surgical patients under epidural].

OBJECTIVE: To explore the effects of propofol sedation on psychological stress in patients undergoing surgery under epidural anesthesia. METHODS: Sixty patients scheduled to undergo elective ileostomy closure under epidural anesthesia were randomized into propofol sedation group and control group (n=30). The patients in the sedation group received a loading dose of propofol of 0.6 mg·kg- 1· h- 1 followed by a maintenance dose with continuous infusion of 3 mg·kg- 1· h- 1 given after the Observer's Assessment of Alertness/Sedation (OAA/S) score reached 2-3. An equivalent volume of normal saline was administered in patients in the control group. The patients' preoperative and intraoperative anxiety scores were assessed with the State Anxiety Inventory (SAI) on the day before and on the first day after the surgery, respectively. The mean blood pressure (MBP), heart rate (HR), SpO2, OAA/S, and the indicators of psychological stress of brain functional state of the patients (including the wavelet index [WLi], anxiety index [ANXi], comfortable index [CFi] and pain index [Pi]) were recorded at 5 min after entering the operating room (T0), at the time of lumbar puncture (T1) and change to supine position after the puncture (T2), at 20 s (T3), 40 s (T4), and 60 s (T5) after intravenous administration, and at 2 min (T6), 4 min (T5), 6 min (T8), 8 min (T9), 10 min (T10) and 40 min (T11) after skin incision. The patient's satisfaction with anesthesia was assessed with the Visual Analog Scale (VAS) score on the first day after the operation. Serum cortisol level was measured before anesthesia and at the end of operation to calculate the changes in cortisol level. RESULTS: The two groups of patients were comparable for preoperative SAI scores (P>0.05); The patients in the sedation group appeared to have lower intraoprative SAI scores, but this difference was not statistically significant (P=0.05). MBP, HR, and SpO2 at the time points from T6 to T10 and OAA/S, WLi, ANXi, CFi, and Pi at the time points from T6 to T11 were significantly lower in the sedation group (all P < 0.05), and these parameters were not significantly different between the two groups at the other time points (all P>0.05). The patient satisfaction scores were significantly higher in the sedation group (Z=2.07, P < 0.05). Compared with the preoperative levels, serum cortisol level at the end of the operation was increased in the sedation group but lowered in the control group, and the variations of serum cortisol level differed significantly between the two groups (t=4.75, P < 0.01). CONCLUSIONS: Intraoperative propofol sedation can alleviate the patients' anxiety, improve the comfort level, and lessen physiological stress during surgeries under epidural anesthesia.

Screening and identification of a specific peptide for targeting hypoxic hepatoma cells.

The biological behaviors of residual hepatoma cells after transarterial embolization therapy, which exist in a hypoxic or even anaerobic tumor microenvironment, differ from the tumor cells under normoxic conditions. This study aimed to use a phage display peptide library for in vivo and in vitro screening to obtain a peptide which could specifically bind to hypoxic hepatoma cells, allowing further targeted diagnosis and treatment for liver cancer. In this study, hypoxic hepatoma cells HepG2 (targeted cells), and normal liver cells HL-7702 (control cells), were utilized to perform three rounds of in vitro screening using a phage-displayed 7-mer peptide library. In addition, hypoxic HepG2 were subcutaneously injected into nude mice to establish a hepatocarcinoma model, followed by performing three rounds of in vivo screening on the phages identified from the in vitro screening. The products from the screening were further identified using ELISA and immunofluorescence staining on cells and tissues. The results indicated that the P11 positive clone had the highest binding effect with hypoxic hepatoma cells. The sequence of the exogenous insert fragment of P11 positive clone was obtained by sequencing: GSTSFSK. The binding assay indicated that GSTSFSK could specifically bind to hypoxic hepatoma cells and hepatocarcinoma tissues. This 7-mer peptide has the potential to be developed as an useful molecular to the targeting diagnosis and treatment of residual hepatoma cells after transarterial chemoembolization.

Effects of plasma collected 48 hours after transient limb ischemia on blood pressure recovery in homogenic rats after myocardial ischemia reperfusion in vivo.

BACKGROUND: Whether plasma can transfer the protective effect(s) of remote ischemic preconditioning (RIPC) between animals remains unresolved. We therefore investigated the effects of plasma collected 48 hours after transient limb ischemia on blood pressure recovery during myocardial ischemia reperfusion (IR) in homogenic rats. METHODS: Plasma was collected from Lewis rats, and the donor rats were randomly assigned to 2 groups: transient limb ischemia and control (n = 8 each). Transient limb ischemia was achieved by four cycles of 5-minute ischemia and 5-minute reperfusion by noninvasive ligation and deligation of the both legs using elastic rubber bands after anesthesia. In the control group, no ligation was performed. Forty-eight hours later, whole blood was collected, and the plasma spun off. Study Lewis rats underwent 30-minute left anterior descending coronary artery occlusion followed by 180-minute reperfusion, and were randomly assigned to 2 groups (group A and group B, n = 24 each), each further subdivided into 3 subgroups (n = 8 each). The subgroups of group A received normal saline (group A1) , plasma of control rats (group A2), plasma of transient limb ischemia rats (group A3) respectively at 1 hour before IR; the subgroups of group B received normal saline (group B1), plasma of control rats (group B2), plasma of transient limb ischemia rats (group B3) respectively at 24 hours before IR. BIOPAC systems were used to measure hemodynamics of rats during myocardial ischemiareperfusion. RESULTS: Systolic blood pressure (SBP) after IR in group B3 was different from that in groups B1 and B2 (B3 vs. B1, P = 0.007; B3 vs. B2, P = 0.039) at the beginning of reperfusion and 30 minutes after reperfusion. SBP was higher in group B3 than in groups B1 and B2 at the beginning of perfusion (B3 vs. B1, P = 0.010; B3 vs. B2, P = 0.002) and 30 minutes after reperfusion (B3 vs. B1, P = 0.001; B3 vs. B2, P = 0.001). SBP did not differ among subgroups A1, A2 and A3. Diastolic blood pressure and heart rate did not change in group A or group B. CONCLUSIONS: The transfusion of plasma collected 48 hours after transient limb ischemia into homogenic rats 24 hours before IR can improve the SBP recovery during reperfusion. This may suggest that cardioprotective effect of late phase of RIPC is transferable via plasma.