Effect of esketamine on the EC50 of remifentanil for blunting cardiovascular responses to endotracheal intubation in female patients under general anesthesia: a sequential allocation dose-finding study.

BACKGROUND: This study aimed to investigate the effect of esketamine on the dose-effect relationship between remifentanil and the cardiovascular response to endotracheal intubation during target-controlled infusion (TCI) of propofol. METHODS: Patients underwent elective gynecological laparoscopic surgery under general anesthesia with endotracheal intubation, aged 18-65 years, American Society of Anesthesiologists class I or II, 18 kg/m2 ≤ body mass index ≤ 30 kg/m2, were randomly divided into the control (group C) and esketamine groups (group E). Before anesthesia induction, group E received an intravenous injection of 0.3 mg/kg of esketamine, while group C received an equal dose of physiological saline. TCI of propofol to the effect-site concentration (EC) of 3.0 µg/mL, and then TCI of remifentanil to the effect room and intravenous injection of rocuronium 0.6 mg/kg after MOAA/S was 0. Endotracheal intubation was performed after 2 min. Dixon's modified sequential method was used, and the initial EC of remifentanil was 3.0 ng/mL. The EC of remifentanil was determined according to the intubation response of the previous patient, with an adjacent concentration gradient of 0.3 ng/mL. The EC50 and EC95 values and their 95% confidence intervals (CIs) were determined using probit regression analysis. RESULTS: The EC50 for cardiovascular response inhibition to endotracheal intubation using remifentanil was 3.91 ng/mL (95% CI: 3.59-4.33 ng/mL) and EC95 was 4.66 ng/mL (95% CI: 4.27-6.23 ng/mL) with TCI of propofol 3.0 µg/mL. After intravenous administration of 0.3 mg/kg of esketamine, the EC50 of remifentanil was 3.56 ng/mL (95% CI: 3.22-3.99 ng/mL) and EC95 was 4.31 ng/mL (95% CI: 3.91-5.88 ng/mL). CONCLUSIONS: Combined with TCI of propofol 3.0 µg/mL for anesthesia induction, esketamine significantly reduced the EC50 and EC95 of remifentanil to inhibit the cardiovascular response to endotracheal intubation. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trials Registry ( www.chictr.org.cn ; registration number: ChiCTR2200064932; date of registration:24/10/2022).

A Systematic Scoping Review on Dignity Assessment Tools.

CONTEXT: The provision of person-centered dignity-conserving care is central to palliative care. It is important to reevaluate current methods of assessing dignity as the concept of dignity is multifaceted. OBJECTIVES: The aim of this study is to understand the tools which are used to assess a patient's dignity and the elements of dignity evaluated in these tools. METHODS: Two independent and concurrent Systematic Evidence-Based Approach guided systematic scoping reviews (SSR in SEBA) on existing dignity assessment tools and on accounts of assessments of dignity were carried out. The SSR in SEBA on dignity assessment tools involving PubMed, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Scopus, and CINAHL databases saw 22 full-text articles included from the 645 articles reviewed. The SSR in SEBA on accounts of assessments of dignity featured in the PubMed database identified 102 full-text articles which saw 46 articles included. RESULTS: The domains identified were factors affecting patients' definition of dignity; elements of dignity-conserving care; and components of effective tools. CONCLUSION: Current accounts to assess dignity and assessment tools fail to capture shifting self-concepts of dignity holistically. A portfolio-like appraisal of dignity is proposed to achieve assessments that are timely, longitudinal, and patient-specific. Portfolio-based assessments by members of the multidisciplinary team will better direct timely evaluations of relevant aspects of changing concepts of dignity, without losing the patient's holistic perception of dignity.

[Effect of LncRNA GATA3-AS1 Targeting MiR-515-5p on Cell Proliferation and Apoptosis in Childhood Acute Lymphoblastic Leukemia Cells].

OBJECTIVE: To investigate the effects of long non-coding RNA (lncRNA) GATA3 antisense RNA 1 (GATA3-AS1) targeting miR-515-5p on the proliferation and apoptosis of childhood acute lymphoblastic leukemia (ALL) cells. METHODS: RT-qPCR was used to determine the expression of GATA3-AS1 and miR-515-5p in the plasma of controls and ALL children. Human ALL cells Jurkat were divided into si-GATA3-AS1, si-NC, miR-NC, miR-515-5p, si-GATA3-AS1+anti-miR-NC and si-GATA3-AS1+anti-miR-515-5p groups. CCK-8 assay was used to detect the cell proliferation, and flow cytometry was used to detect the cell apoptosis. The targeting relationship between GATA3-AS1 and miR-515-5p was determined by dual-luciferase reporter assay. RESULTS: The expression level of GATA3-AS1 in the plasma of ALL children was significantly higher than that of controls (P <0.001), while the expression level of miR-515-5p was significantly lower than that of controls (P <0.001). Compared with the si-NC group, the cell inhibition rate, apoptosis rate, and miR-515-5p expression level in si-GATA3-AS1 group were significantly increased (P <0.001). Compared with the miR-NC group, the cell inhibition rate and apoptosis rate in miR-515-5p group were significantly increased (P <0.001). GATA3-AS1 could directly and specifically bind to miR-515-5p. Compared with the si-GATA3-AS1+anti-miR-NC group, the cell inhibition rate and apoptosis rate in si-GATA3-AS1+anti-miR-515-5p group were significantly decreased (P <0.001). CONCLUSION: Down-regulation of GATA3-AS1 can inhibit proliferation and induce apoptosis of childhood ALL cells by targeting up-regulation of miR-515-5p expression.

A Systematic Review of Stakeholder Perspectives of Dignity and Assisted Dying.

INTRODUCTION: The debate on assisted dying and its components, euthanasia and physician-assisted suicide has evolved with the emergence of the right to dignity and the wish to hasten death (WTHD). Whilst shaped by local legal and sociocultural considerations, appreciation of how patients, healthcare professionals and lawmakers relate notions of dignity to self-concepts of personhood and the desire for assisted dying will better inform and direct support of patients. METHODS: Guided by the Systematic Evidence Based Approach, a systematic scoping review (SSR in SEBA) on perspectives of dignity, WTHD and personhood featured in PubMed, Embase, PsycINFO, Cochrane Database of Systematic Reviews, CINAHL, Scopus databases and four key Palliative Care journals was conducted. The review hinged on the following questions: "what is the relationship between dignity and the wish to hasten death (WTHD) in the assisted dying debate?", "how is dignity conceptualised by patients with WTHD?" and "what are prevailing perspectives on the role of assisted dying in maintaining a dying patient's dignity?" RESULTS: 6947 abstracts were identified, 663 full text articles reviewed, and 88 articles included. The four domains identified include 1) concepts of dignity through the lens of the Ring Theory of Personhood (RToP) including their various definitions and descriptions; 2) the relationship between dignity, WTHD and assisted dying with loss of dignity and autonomy foregrounded; 3) stakeholder perspectives for and against assisted dying including those of patient, healthcare provider and lawmaker; and 4) other dignity-conserving measures as alternatives to assisted dying. CONCLUSION: Concepts of dignity constantly evolve throughout the patient's end of life journey. Understanding when and how these concepts of personhood change and trigger the fear of a loss of dignity or intractable suffering could direct timely, individualised and appropriate person-centred dignity conserving measures. We believe an RToP-based tool could fulfil this role and further study into the design of this tool is planned.

Targeted Perioperative Nursing Combined with Propofol and Fentanyl for Gynecological Laparoscopic Surgery.

Objective: The aim of this study is to investigate the clinical effects of targeted perioperative nursing combined with propofol and fentanyl in gynecological laparoscopic surgery. Methods: Patients who were admitted to our hospital for gynecological laparoscopic surgeries from October 1, 2019 to November 30, 2021 were included in this retrospective study. Patients in group A received routine propofol and fentanyl. Patients in group B received targeted perioperative nursing on the basis of interventions in group A. The anesthetic effects, clinical indicators, mental health status, and adverse reactions were compared between the two groups. Results: A total of 84 qualified patients were retrieved. The total effective anesthesia rate, extubation time, operation time, consciousness recovery time, intraoperative blood loss, hospital stay, SAS score, SDS score, health status indicators, and adverse events in group B were all significantly better than those in group A (P < 0.05 for all comparisons). Conclusion: Combined intervention (propofol + fentanyl + targeted perioperative care) for gynecological laparoscopic surgery patients has a significant anesthesia effect, which can effectively improve the patient's clinical indicators and mental health status and can also reduce the occurrence of adverse events. It has good safety and can be widely used in clinical practice.

Estrogen Enhances the Microvascular Reactivity Through RhoA-ROCK Pathway in Female Mice During Hemorrhagic Shock.

ABSTRACT: Vascular hypo-reactivity plays a critical role inducing organ injury during hemorrhagic shock. 17ß-estradiol (E2) can induce vasodilation to increase blood flow in various vascular beds. This study observed whether E2 can restore vascular hypo-reactivity induced by hemorrhagic shock, and whether E2 effects are associated with RhoA-Rho kinase (ROCK)-myosin light chain kinase phosphatase (MLCP) pathway. The hemorrhagic shock model (40 ±â€Š2 mm Hg for 1 h, resuscitation for 4 h) was established in ovary intact sham operation (OVI), ovariectomized (OVX), and OVX plus E2 supplement female mice. Intestinal microvascular loop was used to assess blood flow in vivo, mRNA expression and vascular reactivity in vitro. Hemorrhagic shock significantly reduced norepinephrine microvascular reactivity. Decreased microvascular reactivity was exacerbated by OVX and reversed by E2 supplement. U-46619 (RhoA agonist) increased microvascular reactivity, and C3 transferase (an ADP ribosyl transferase that selectively induces RhoA ribosylation) or Y-27632 (ROCK inhibitor) inhibited sham mice microvascular reactivity. Similarly, U-46619 increased microvascular reactivity in OVI and OVX mice following hemorrhagic shock, which was abolished by Y-27632 or concomitant incubation of okadaic acid (OA) (MLCP inhibitor) and Y-27632. In OVX plus E2 supplement mice with hemorrhagic shock, Y-27632 inhibited microvascular reactivity, which was abolished by concomitant U-46619 application. Lastly, hemorrhagic shock remarkably decreased intestinal loop blood flow, RhoA and ROCK mRNA expressions in vascular tissues in OVX females, but not in OVI females, which were reversed by E2 supplement. These results indicate that estrogen improves microvascular reactivity during hemorrhagic shock, and RhoA-ROCK signaling pathway may mediate E2 effects.

Notoginsenoside R1 attenuates breast cancer progression by targeting CCND2 and YBX3.

BACKGROUND: Breast cancer (BC) is a common malignancy with highly female incidence. So far the function of notoginsenoside R1 (NGR1), the extract from Panax notoginseng, has not been clearly elucidated in BC. METHODS: Optimal culture concentration and time of NGR1 were investigated by cell counting kit-8 assay. Cell proliferation ability was measured by colony formation assays. Transwell assay was used to detect the effect of NGR1 on cell migration and invasion. The apoptosis rate of cells between each group was measured by TUNEL assay. RESULTS: NGR1 treatment has an inhibitory effect on proliferation, migration, invasion, and angiogenesis and a stimulating effect on cell cycle arrest and apoptosis of Michigan Cancer Foundation-7 (MCF-7) cells. The 50% growth inhibitory concentration for MCF-7 cells at 24 h was 148.9 mmol/L. The proportions of MCF-7 cells arrested in the G0/G1 phase were 36.94±6.78%, 45.06±5.60%, and 59.46±5.60% in the control group, 75, and 150 mmol/L groups, respectively. Furthermore, we revealed that NGR1 treatment attenuates BC progression by targeted downregulating CCND2 and YBX3 genes. Additionally, YBX3 activates phosphatidylinositol 3-phosphate kinase (PI3K)/protein kinase B (Akt) signaling pathway by activating kirsten rat sarcoma viral oncogene, which is an activator of the PI3K/Akt signaling pathway. CONCLUSION: These results suggest that NGR1 can act as an efficacious drug candidate that targets the YBX3/PI3K/Akt axis in patients with BC.

Identification of C-geranylated flavonoids from Paulownia catalpifolia Gong Tong fruits by HPLC-DAD-ESI-MS/MS and their anti-aging effects on 2BS cells induced by H2O2.

The fruits of Paulownia catalpifolia Gong Tong are used as a Chinese folk herbal medicine for the treatment of enteritis, tonsillitis, bronchitis, and dysentery, etc. Our previous study has identified new C-geranylated flavanones with obvious anti-proliferative effects in lung cancer A549 cells. In the present study, a new C-geranylated flavone, paucatalinone C (1) and five known C-geranylated flavanones (2-6) were isolated. In addition, a total of 34 C-geranylated flavonoids were detected by HPLC-DAD-ESI-MS/MS coupling techniques from the CH2Cl2 extract of P. catalpifolia. Futhermore, anti-aging effects of isolated compounds were evaluated in vitro with premature senescent 2BS cells induced by H2O2. Phytochemical results indicated that P. catalpifolia was a natural resource of abundant C-geranylated flavonoids. Diplacone (3) and paucatalinone A (5) were the potent anti-aging agents in the premature senescent 2BS cells induced by H2O2 and the C-geranyl substituent may be an important factor because of its lipophilic character.

New geranylated flavanones from the fruits of Paulownia catalpifolia Gong Tong with their anti-proliferative activity on lung cancer cells A549.

Three new geranylated flavanones, named as paucatalinone A (1), B (2), and isopaucatalinone B (3), were isolated from the fruits of Paulownia catalpifolia Gong Tong (Scrophulariaceae). Their structures were well determined by means of IR, MS, 1D and 2D NMR, and CD techniques. Paucatalinone A (1) is the first sample as a dimeric geranylated flavanone derivative isolated from natural products. Paucatalinone A (1) displayed good antiproliferative effects on human lung cancer cells A549 and resulted in a clear increase of the percentage of cells in G1 phase and a decrease in the percentage of cells in S and G2/M phases in comparison with control cells.

Curcumin ameliorates dextran sulfate sodium-induced experimental colitis by blocking STAT3 signaling pathway.

BACKGROUND AND AIMS: Although a series of studies have shown that curcumin can exert anti-inflammatory effects in colitis by inhibiting NF-κB activation, whether these anti-inflammatory effects of curcumin are also attributed to its ability to inhibiting STAT3 pathway has never been tested in experimental colitis to date. The purpose of the study was to investigate whether curcumin could exert its therapeutic effects in experimental colitis by inhibiting STAT3 pathway. MATERIALS AND METHODS: Curcumin was administered in experimental colitis induced by dextran sulfate sodium (DSS). The disease activity index (DAI) and histological score were observed. The phospho-STAT3 was assessed by western blot analysis. The DNA-binding activity of STAT3 dimers was evaluated by electrophoretic mobility shift assay (EMSA). The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß was measured by enzyme-linked immunosorbent assay. Myeloperoxidase (MPO) activity was determined by using MPO assay kit. RESULTS: A significant improvement was observed in DAI and histological score in mice with curcumin, and the increases in phospho-STAT3 activity, DNA-binding activity of STAT3 dimers, MPO activity, IL-1ß, and TNF-α expression in mice with DSS-induced colitis were significantly reduced following treatment with curcumin. CONCLUSION: Curcumin exerts beneficial effects in experimental colitis by the suppression of STAT3 pathway, which may therefore provide a better understanding of the mechanism of action for curcumin in treating colitis.

[Effects of PI3K/AKT inhibitor wortmannin on proliferation and apoptosis of primary porcine preadipocytes].

The purpose of this study was to determine the proper concentration of wortmannin that effectively inhibits PI3K/AKT but does not affect the proliferation and apoptosis of primary porcine preadipocytes. Firstly, primary porcine preadipocytes were isolated and their abilities to be induced to differentiation into mature adipocytes were evaluated. The preadipocytes were then treated with different concentrations of wortmannin, and the proliferation of the cells was detected with methanethiosulfonate (MTS). Annexin V- FITC/PI double-staining was used to detect the level of cell apoptosis. The apoptosis-related gene expressions were also quantified by qRT-PCR. At the same time, single cell electrophoresis was used to examine the extent of cellular DNA damage. Our data demonstrated that the primary porcine preadipocytes could differ-entiate into mature adipocytes. Up to 200 nmol/L of wortmannin had no effect on the proliferation ability of primary porcine preadipocytes (P>0.05). Results from the flow cytometry Annexin V- FITC/PI double-staining showed that 200 nmol/L wortmannin significantly induced apoptosis of the primary porcine preadipocytes (P<0.05). QRT-PCR results also showed that the expressions of caspase8, TNFR1, GZMB, and Bcl-x1 were significantly upregulated, while the expression of GZMA and cFLIP were not significantly affected when treated with 200 nmol/L wortmannin. In addition, results from the single cell gel electrophoresis indicated that 100 nmol/L wortmannin did not induce DNA damage. In conclusion, our results col-lectively showed that 100 nmol/L wortmanin can be used to study the role of PI3k pathway on the preadipocytes differen-tion without affecting the cell proliferation and apoptosis.