Different sedation profiles with ciprofol compared to propofol represented by objective sedation level assessments by BIS and its acute hemodynamic impact in 3 escalated doses of ciprofol and propofol in healthy subjects: a single-center, open-label, randomized, 2-stage, 2-way crossover trial.

OBJECTIVE: To compare the sedation profiles and the pharmacokinetic, pharmacodynamic and safety characteristics of ciprofol and propofol at 3 escalated dose levels in healthy Chinese male subjects. PATIENTS AND METHODS: Eighteen subjects were planned to be enrolled into 3 dose groups in turn: group 1 (ciprofol-0.4 mg/kg vs. propofol-2.0 mg/kg), group 2 (ciprofol-0.6 mg/kg vs. propofol-3.0 mg/kg) and group 3 (ciprofol-0.8 mg/kg vs. propofol-4.0 mg/kg). They were randomly assigned into a ciprofol or propofol group in a ratio of 1:1, with sequences of ciprofol-propofol or propofol-ciprofol, separated with a washout period of at least 48 h. RESULTS: A total of 19 subjects were enrolled and 18 completed the trial. The median time to being fully alert after induction by ciprofol was longer than for propofol. The bispectral index (BIS) recovered significantly slower with ciprofol than with propofol 5 min and 10 min after reaching its lowest points. Systolic blood pressure (group 1: p=0.041; group 2: p=0.015; group 3: p=0.004) and mean arterial pressures (group 1: p=0.026; group 2: p=0.015; group 3: p=0.004) measured by the area under the curve below the baseline during the 2 min after induction were significantly less for ciprofol compared to propofol, but a significant change in diastolic blood pressure was only observed in group 3 (p=0.002). Eighteen (100.0%) subjects experienced 47 ciprofol-related treatment emergent adverse events (TEAEs) and 17 (94.4%) subjects had 54 propofol-related TEAEs, which were mainly hypotension, involuntary movements, respiratory depression, and pain at the injection site with severity of grade 1 or 2. CONCLUSIONS: Ciprofol may be well tolerated at higher doses in the clinical practice and exhibited significantly different sedation profiles to propofol.

Zeb1 Promotes Odontoblast Differentiation in a Stage-Dependent Manner.

A comprehensive study of odontoblastic differentiation is essential to understand the process of tooth development and to achieve the ability of tooth regeneration in the future. Zinc finger E-box-binding homeobox 1 (Zeb1) is a transcription factor expressed in various neural crest-derived tissues, including the mesenchyme of the tooth germ. However, its role in odontoblastic differentiation remains unknown. In this study, we found the expression of Zeb1 gradually increased during odontoblast differentiation in vivo, as well as during induced differentiation of cultured primary murine dental papilla cells (mDPCs) in vitro. In addition, the differentiation of mDPCs was repressed in Zeb1-silenced cells. We used RNA sequencing (RNA-seq) to identify the transcriptome-wide targets of Zeb1 and used assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) to explore the direct targets of Zeb1 in both the early stage (embryonic day 16.5; E16.5) and the late stage (postnatal day 0; PN0) of tooth development. We identified the motifs of transcription factors enriched in Zeb1-dependent accessible chromatin regions and observed that only in the early stage of mDPCs could Zeb1 significantly change the accessibility of chromatin regions. In vivo and in vitro experiments confirmed that silencing of Zeb1 at E16.5 inhibited dentinogenesis. Analysis of RNA-seq and ATAC-seq resulted in the identification of Runx2, a gene directly regulated by Zeb1 during early odontoblast differentiation. Zeb1 enhances the expression of Runx2 by binding to its cis-elements, and ZEB1 interacts with RUNX2. In the late stage of tooth development, we found that ZEB1 could directly bind to and increase the enhancer activity of an element upstream of Dspp and promote dentinogenesis. In this study, for the first time, we revealed that ZEB1 promoted odontoblast differentiation in the early stage by altering chromatin accessibility of cis-elements near genes such as Runx2, while in the late stage, it directly enhanced Dspp transcription, thereby performing a dual role.

Correlation between peripheral skeletal muscle functions and the stable phase of COPD in older patients.

OBJECTIVE: To establish normal values for detection indexes of peripheral skeletal muscle dysfunction (quadriceps femoris) of healthy older subjects, and investigate the functional status of the peripheral skeletal muscle of patients with stable phase COPD. PATIENTS AND METHODS: Patients with stable phase COPD and healthy subjects of similar age were included. The assessments of strength and myoelectricity of the quadriceps femoris were recorded. The twitch tension of the quadriceps femoris (TwQ), quadriceps maximum voluntary contraction (QMVC), and endurance time (Tf) were measured. The multiple-parameter malnutrition index (MNI) was used for overall evaluation of the nutritional status of patients. The femoral muscle volume was estimated. All subjects were subjected to a routine pulmonary function test including indexes such as FEV1, FVC, FEV1/FVC (%), and PEF. Enzyme-linked immunoassay (ELISA) was used to measure the levels of myostatin, tumor necrosis factor-α, TNF-like apoptosis-inducing factor (TWEAK), surface active protein D (SPD), C-reactive protein (CRP), interleukin (IL)-1ß, and IL-6. The cell immunohistochemical method was used to detect the expression of nuclear factor Kappa B (NF-κB). RESULTS: There were significant differences in body weight, BMI, femoral muscle volume, and physical activity scores between the two groups (p<0.01). The MNI of patients in the COPD group was significantly higher than that in the control group (p<0.01). The QMVC of 51 male and 16 female patients decreased. All eight tested cytokines increased in the COPD group but there were only significant differences in four cytokines (p<0.05). CONCLUSIONS: Chronic systemic inflammation is a major risk factor of skeletal muscle dysfunction (SMD) in COPD patients. The levels of SPD, myostatin, TWEAK, and TNF-α decreased significantly in COPD patients.

Retinervus luffae fructus (RLF): a novel material for use in negative pressure wound therapy.

OBJECTIVE: To describe a modified negative pressure wound therapy (NPWT) apparatus, made mainly of an environmentally-friendly material derived from the retinervus luffae fructus (RLF; or loofah) plant. METHOD: We retrospectively reviewed the charts of patients with skin defects on their limbs who underwent treatment with the RLF-NPWT device from September 2012 to October 2012. The endpoint of the study was healing by secondary intention; the time (days) to endpoint was evaluated. RESULTS: The RLF-NPWT device was used in 16 patients. The age of the patients ranged from 15-82 years, with a mean age of 43 ± 17 years. Six patients sustained crush injuries, nine patients had open limb injuries from motor vehicle accidents and a further patient had a diabetic foot ulcer. The mean time to healing was 8.5 ± 2.4 days. Following RLF-NPWT, fresh granulation tissue was observed in all wound beds, with no evidence of macroscopical necrosis. All 16 patients in the study achieved secondary healing. CONCLUSION: The environmentally friendly RLF-NPWT apparatus is easy to use and able to provide continual negative pressure for optimal preparation of the wound bed. The cost-effectiveness of RLF-NPWT compared to standard NPWT requires further investigation. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no conflicts of interest to declare.