Diagnostic performance of coronary computed tomography angiography stenosis score for coronary stenosis.

BACKGROUND: Coronary computed tomography angiography stenosis score (CCTA-SS) is a proposed diagnosis score that considers the plaque characteristics, myocardial function, and the diameter reduction rate of the lesions. This study aimed to evaluate the diagnostic performance of the CCTA-SS in seeking coronary artery disease (CAD). METHODS: The 228 patients with suspected CAD who underwent CCTA and invasive coronary angiography (ICA) procedures were under examination. The diagnostic performance was evaluated with the receiver operating curve (ROC) for CCTA-SS in detecting CAD (defined as a diameter reduction of ≥ 50%) and severe CAD (defined as a diameter reduction of ≥ 70%). RESULTS: The area under ROC (AUC) of CCTA-SS was 0.909 (95% CI: 0.864-0.943), which was significantly higher than that of CCTA (AUC: 0.826; 95% CI: 0.771-0.873; P = 0.0352) in diagnosing of CAD with a threshold of 50%. The optimal cutoff point of CCTA-SS was 51% with a sensitivity of 90.66%, specificity of 95.65%, positive predictive value of 98.80%, negative predictive value of 72.13%, and accuracy of 91.67%, whereas the optimal cutoff point of CCTA was 55%, and the corresponding values were 87.36%, 93.48%, 98.15%, 65.15%, and 88.60%, respectively. With a threshold of 70%, the performance of CCTA-SS with an AUC of 0.927 (95% CI: 0.885-0.957) was significantly higher than that of CCTA with an AUC of 0.521 (95% CI: 0.454-0.587) (P < 0.0001). CONCLUSIONS: CCTA-SS significantly improved the diagnostic accuracy of coronary stenosis, including CAD and severe CAD, compared with CCTA.

Effects and mechanisms of perioperative medications on the hypothalamic pituitary adrenal response to surgical injury: A narrative review.

The adrenal gland is a vital endocrine organ, and adrenal steroid synthesis and secretion are closely regulated by the hypothalamic-pituitary-adrenal (HPA) axis in response to various stimuli. Surgery or trauma can activate the HPA axis and induce the secretion of cortisol. Different cortisol responses vary with the grade of surgery. Perioperative medications have the potential to decrease the cortisol level in the body, and both excessive and insufficient cortisol levels after surgery are disadvantageous. The effect of perioperative medications on the HPA response to surgery can be divided into three levels: "adrenal insufficiency (AI)", "stress response inhibition", and "uncertainty". The clinical presentation of AI includes fatigue, nausea, vomiting, abdominal pain, muscle cramps, hypotension, hypovolemic shock and prerenal failure, which may result in fatal consequences. Stress response inhibition can reduce postoperative complications, such as pain and cognitive dysfunction. This is protective to patients during perioperative and postoperative periods. The aim of the present review is to shed light on current evidence regarding the exact effects and mechanisms of perioperative medications on the HPA response to surgical injury and provide the applicable guidance on clinical anesthesia.

Bibliometric and visualized analysis of research relating to minimally invasive spine surgery reported over the period 2000-2022.

Background: Since entering the 21st century, there has been an increasing interest in minimally invasive surgery for spinal diseases, which has led to the continued development of minimally invasive spine surgery (MISS), with major breakthroughs in technology and technical skills. However, in recent years, there is little relevant research using bibliometrics to analyze the field of MISS research. The purpose of this study is to sort out the publication situation and topic trends of articles in the field of MISS research from the perspective of bibliometrics. Methods: The articles and reviews related to MISS from 2000 to 2022 were retrieved and downloaded from the Web of Science Core Collection (WOSCC). Visualization and knowledge mapping were performed using three bibliometric tools, including online bibliometric platform, CiteSpace and VOSviewer software. Curve fitting and correlation analysis were performed using Microsoft Excel software. The global research publication output, contributions of countries, institutions, authors, and journals, average citations per item (ACI), Hirsch index (H-index), research hot keywords, etc., in this field were analyzed. Results: A total of 2384 papers were retrieved, including 2135 original papers and 249 review papers. In the past 22 years, the number of annual publications of MISS research has shown a steady growth trend. China contributed the most papers, and the United States ranked second, but the United States had the highest total citations, and H-index value. The most prolific institutions were Soochow University, Capital Medical University and Wooridul Spine Hospital. In this field, Professors Lee SH, Ahn Y and Yang HL have made significant achievements. However, there is relatively little international collaboration between institutions or researchers. World Neurosurgery is the most published journal on MISS research. According to the keyword co-occurrence analysis, recent keywords mainly focus on researches on minimally invasive modalities, techniques and prognosis, while on the keyword analysis of the ongoing bursts, percutaneous transforaminal endoscopic discectomy, lumbar diskectomy, spinal stenosis, recompression, diskectomy, endoscopic spine surgery, laminectomy, transforaminal lumbar interbody fusion, etc., will likely continue to be a research hotspot in the near future. Conclusion: Looking at the temporal trend in the number of publications per year, the number of publications for the MISS study will increase in the near future. China has the highest number of publications, but the US has the highest quality publications. International cooperation needs to be further strengthened. Our findings can provide useful information for the academic community and identify possible research fronts and hotspots in the coming years.

Etomidate-Induced Myoclonus in Sprague-Dawley Rats Involves Neocortical Glutamate Accumulation and N -Methyl- d -Aspartate Receptor Activity.

BACKGROUND: Etomidate-induced myoclonus, a seizure-like movement, is of interest to anesthetists. However, its origin in the brain and its underlying mechanism remain unclear. METHODS: Adult male Sprague-Dawley rats were anesthetized with etomidate, propofol, or lidocaine plus etomidate. We assessed the incidence of myoclonus, behavioral scores, and levels of glutamate and γ-aminobutyric acid (GABA) in the neocortex and hippocampus. To determine the origin and how N -methyl- d -aspartate receptors (NMDARs) modulate etomidate-induced neuroexcitability, the local field potential and muscular tension were monitored. Calcium imaging in vitro and immunoblotting in vivo were conducted to investigate the mechanisms underlying myoclonus. RESULTS: The incidence of etomidate (1.5 mg/kg in vivo)-induced myoclonus was higher than that of propofol (90% vs 10%, P = .0010) and lidocaine plus etomidate (90% vs 20%, P = .0050). Etomidate at doses of 3.75 and 6 mg/kg decreased the mean behavioral score at 1 (mean difference [MD]: 1.80, 95% confidence interval [CI], 0.58-3.02; P = .0058 for both), 2 (MD: 1.60, 95% CI, 0.43-2.77; P = .0084 and MD: 1.70, 95% CI, 0.54-2.86; P = .0060), 3 (MD: 1.60, 95% CI, 0.35-2.85; P = .0127 and MD: 1.70, 95% CI, 0.46-2.94; P = .0091) minutes after administration compared to etomidate at a dose of 1.5 mg/kg. In addition, 0.5 and 1 µM etomidate in vitro increased neocortical intracellular calcium signaling; this signaling decreased when the concentration increased to 5 and 10 µM. Etomidate increased the glutamate level compared to propofol (mean rank difference: 18.20; P = .003), and lidocaine plus etomidate (mean rank difference: 21.70; P = .0002). Etomidate in vivo activated neocortical ripple waves and was positively correlated with muscular tension amplitude (Spearman's r = 0.785, P < .0001). Etomidate at 1.5 mg/kg decreased the K-Cl cotransporter isoform 2 (KCC2) level compared with propofol (MD: -1.15, 95% CI, -1.47 to -0.83; P < .0001) and lidocaine plus etomidate (MD: -0.64, 95% CI, -0.96 to -0.32; P = .0002), DL-2-amino-5-phosphopentanoic acid (AP5) suppressed these effects, while NMDA enhanced them. CONCLUSIONS: Etomidate-induced myoclonus or neuroexcitability is concentration dependent. Etomidate-induced myoclonus originates in the neocortex. The underlying mechanism involves neocortical glutamate accumulation and NMDAR modulation and myoclonus correlates with NMDAR-induced downregulation of KCC2 protein expression.

Assessment of lake area in response to climate change at varying elevations: A case study of Mt. Tianshan, Central Asia.

Changes in lake area (water surface area) are often considered accurate and sensitive representations of climate change. However, the role that elevation plays in this dynamic is somewhat unclear; studies remain inconclusive as to whether lake responses are consistent across elevation gradients. Here, we used Landsat and keyhole satellite images to quantify lake area changes from the 1960s to 2020 at different elevations in Central Asia's Tianshan Mountains and relate them to both climatic and anthropogenic factors. The results revealed that all low-elevation lakes showed a decreasing trend, and the total area of all monitored low-elevation lakes was reduced by 18.50 %. The total area of the mid-elevation lakes decreased by 0.16 %, while the total area of the high-elevation glacial lakes increased by 4.35 %. Lakes are recharged by a variety of influxes including glacial meltwater and precipitation. Notably, human activities (urban and agricultural water consumption) were the dominant factors in the shrinkage of low-elevation lakes. Climatic factors were the main driving factors of mid-elevation lake changes, and these lakes appeared to be more sensitive to temperature changes than lakes at other elevations. In addition, significant warming dominated area changes in high-elevation proglacial and unconnected glacial lakes. Overall, those results emphasized that when using lakes to reconstruct paleoclimates or predict lake evolution, it is necessary to consider how elevation gradients and recharge types may affect lake sensitivity to variations in climatic and anthropogenic activity.

The preclinical pharmacological study of a novel intravenous anesthetic, ET-26 hydrochloride, in aged rats.

Background: ET-26 hydrochloride (ET-26HCl) is a novel analogue of etomidate approved for clinical trials. However, all results from recent studies were accomplished in young adult animals. The objective of this study was to evaluate the efficacy and safety of ET-26HCl in aged rats. Methods: Aged Sprague-Dawley rats were randomly divided into three groups (three males and three females in each group) were given dose of two-fold of median effective dose (ED50) of ET-26HCl, etomidate and propofol: the measurements of loss of the righting reflex (LORR) and cardiovascular and respiratory function after injection at the two-fold dose of the median effective dose were used for evaluation of effectiveness and safety, and the modified adrenocorticotropic hormone-stimulation experiment was used to evaluate the inhibition effect of the drugs on the synthesis of adrenal cortical hormones. Results: There was no significant difference in the onset time among propofol, etomidate and ET-26HCl. The duration of propofol (850.5 ± 77.4 s) was significantly longer than that caused by etomidate (489.8 ± 77.0 s, p = 0.007) and ET-26HCl (347.3 ± 49.0 s, p = 0.0004). No significant difference was observed in the time to stand and normal activity among drugs. A total of 66.7% of rats in the ET-26HCl group were evaluated to have mild hematuria. Then, etomidate and ET-26HCl had a milder blood pressure inhibition effect than propofol. Apnea was observed in all rats administered propofol and the duration for this side effect was 45.0 ± 9.0 s. For etomidate and ET-26HCl, no apnea was observed. No other clinical signs of side-effect were observed, and no rats died. No significant difference was observed in corticosterone concentrations between ET-26HCl and solvent group. However, rats administered etomidate had lower corticosterone concentrations than those administered ET-26HCl at 15, 30, and 60 min. Conclusions: Our results indicate ET-26HCl in aged rats is an effective sedative-hypnotic with stable myocardial and respiratory performance and also have mild adrenocortical suppression. Thus, these findings increase the potential for the clinical use of ET-26HCl in the elderly population.

E161111 is an ultra-short-acting etomidate analogue with stable haemodynamics that elicits only slight adrenocortical suppression in rats.

Purpose: We report on a novel ultra-short-acting etomidate analogue, E161111, which has the same primary metabolite as etomidate. Methods: The metabolic rate of E161111 was determined in rat plasma and liver homogenate. Rats were infused for 30 or 60 min to maintain light sedation at Richmond Agitation-Sedation Scale (RASS) for -2 to 0 score. Mean arterial pressure (MAP) was monitored during 30 min infusion. The serum corticosterone was determined during and 3 h after infusion as a measure of adrenocortical function. Results: E161111 was not detected in rat plasma at 1 min (t1/2 = 6.69 ± 0.07 s) and in rat liver homogenates at 5 min (t1/2 = 10.20 ± 3.76 s); its main metabolic product was etomidate acid. The recovery time from loss of righting reflex (LORR) was 4.3 ± 1.5 min after 1-h infusion of E161111. During 30 min infusion, E161111 did not cause MAP changes. The stimulated serum corticosterone levels after 1-h infusion of E161111 were significantly higher than that after 1-h infusion of etomidate at all time points tested for the 3 h study. Conclusions: E161111 was metabolised rapidly, the metabolites were same as etomidate, and the recovery time after 1-h infusion was short. It elicited haemodynamic stability and milder suppression of corticosterone than that elicited by etomidate.

Adamgammadex in patients to reverse a moderate rocuronium-induced neuromuscular block.

AIMS: The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients. METHODS: Forty-eight patients aged 18-64 years old were randomized to receive adamgammadex (2, 4, 6, and 8 mg.kg-1 ) or placebo at a ratio of 10:2 for reversal of 0.6 mg.kg-1 rocuronium-induced neuromuscular block. Neuromuscular function was monitored by TOF-Watch® SX. When the T2 of train-of-four (TOF) reappeared at the end of surgery, patients received an intravenous administration of adamgammadex or placebo. RESULTS: The recovery time of the TOF ratio to 0.9 decreased significantly from 39.3 [29.5, 50.2] minutes in the group that received placebo to 3.0 [2.3, 3.9] minutes, P < .0001; 2.1 [1.5, 3.0] minutes, P < .0001; 2.1 [1.8, 3.3] minutes, P < .0001; and 1.8 [1.5, 2.2] minutes, P < .0001 in the 2, 4, 6 and 8 mg.kg-1 adamgammadex groups, respectively. Then, adamgammadex also showed a shortened recovery time for the TOF ratio recovered to 0.8 and 0.7. Adamgammadex was well tolerated, and no cases of anaphylactic reactions, post-operative bleeding, recurarization, abnormal basic vital signs and prolonged QT intervals were observed. The pharmacokinetics of adamgammadex in plasma increased in dose-dependent manner. The 24-hour cumulative fraction of adamgammadex in urine was 65-83%, and that of rocuronium was increased after using adamgammadex from 15% to about 25-30%. CONCLUSION: Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block, and it was safe and well tolerated in patients.

Reconstruction and repair, using mini-plate and bone graft for persons living with HIV with giant cell tumor of long bone: retrospective analysis of a single-center experience.

BACKGROUND: To evaluate the effect of reconstruction and repair, using a mini-plate and bone graft for HIV -positive patients with giant cell tumor of long bone. METHODS: We conducted a retrospective analysis of 12 HIV positive patients with giant cell tumor of long bone. A non-HIV-positive cohort of patients, matched for age, sex, and disease type, was selected as the control group. From June 2012 to August 2020, curettage by ultrasonic scalpel was performed in all patients, combined with min- plate and bone graft treatment. All patients were followed- up for 18 to 60 months. Limb function was evaluated, using the MSTS93 scoring system, and any examples of postoperative recurrence, distant metastasis, complications, MSTS93 score, and fracture prognosis were recorded. RESULTS: The mean age of HIV group was 43.5 years. The ratio of men to women was 11: 1. In all cases the histopathological diagnosis was clear, except the patients with primary malignant giant cell tumor of bone, including five, three, two, and two cases in the proximal tibia, distal femur, distal tibia, and talus, respectively. Following their surgery, all patients were followed up with an average of 31.24 ± 11.84 months. No local recurrence or pulmonary metastases were observed. Post-surgery, all the 12 patients showed good bone morphologic repair and reconstruction, good bone healing, good joint function, and no pathological fractures around their lesion. In the HIV group, one case of giant cell tumor in the proximal tibia showed mild articular surface collapse and mild valgus deformity of the knee joint but retained good joint function. The MSTS scores of excellent or good in the two groups comprised 83.3%, thus, there was no significant difference between them (P > 0.05). Compared with preoperatively, the MSTS scores in the HIV group were significantly improved, ranging from 7 to 11 points preoperatively to 24 to 27 points postoperatively; this difference was statistically significant (P < 0.05). CONCLUSION: Reconstruction and repair, using a mini-plate and bone graft for HIV -positive patients with giant cell tumor of long bone can achieve satisfactory results. The mini- plate requires little space and is flexible during reconstruction and fixation, significantly reducing complications such as surgical site infection, as well as preserving joint function and avoiding amputation; therefore, it is a safe and effective treatment method.

Silencing BLNK protects against interleukin-1ß-induced chondrocyte injury through the NF-κB signaling pathway.

BACKGROUND: Osteoarthritis (OA) is the most common joint disease in the elderly and is characterized by the progressive degeneration of articular cartilage. It is necessary to study the molecular pathology of OA. This study aimed to explore the role and mechanism of BLNK in regulating interleukin-1ß (IL-1ß)-induced chondrocyte injury and OA progression. METHODS: GSE1919 (5 normal samples and 5 OA samples) was downloaded from the Gene Expression Omnibus (GEO) database. The limma package in R software was used to identify differentially expressed genes (DEGs) between control and OA-affected cartilage. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the differentially expressed genes were also performed. Apoptosis was assessed by flow cytometry. An OA rat model was established, and the relative expression of BLNK was assessed by real time quantitative PCR (qRT-PCR) and immunohistochemical staining. The expression of collagen II, MMP9, p65 and p-p65 was measured by Western blot analysis. Moreover, inflammatory factors (TNF-α and IL-18) were assessed by ELISA. The NF-κB inhibitor JSH-23 was used to assess the impact of BLNK on the NF-κB signaling pathway. RESULTS: In total, 1318 DEGs were identified between normal and OA-affected cartilage according to the criteria (P-value <0.05 and |logFC > 1|). These DEGs were mainly enriched in the NF-κB pathway. BLNK was highly expressed in OA cartilage tissue and injured chondrocytes. Silencing BLNK significantly downregulated the IL-1ß-induced apoptosis of chondrocytes. Silencing BLNK partially increased collagen II expression and downregulated MMP13 expression. Moreover, silencing BLNK partially decreased TNF-α and IL-18 expression. BLNK silencing inhibited the activation of NF-κB in OA. Silencing BLNK delayed OA progression through the NF-κB signaling pathway. CONCLUSION: Silencing BLNK delayed OA progression and IL-1ß-induced chondrocyte injury by regulating the NF-κB pathway.

Efficacy and Safety of Fospropofol Disodium for Injection in General Anesthesia Induction for Adult Patients: A Phase 3 Trial.

Background: Fospropofol disodium for injection (FospropofolFD) is a prodrug that is metabolized into propofol to produce a general anesthesia effect when administered intravenously. Objective: This study aimed to assess the efficacy and safety of FospropofolFD in comparison with propofol medium/long-chain fat emulsion injections (propofol-MCT/LCT) for general anesthesia induction in adult patients undergoing elective surgeries. Setting: Nine academic medical centers in China. Method: This multicenter, randomized, double-blind, double-simulated, controlled, and non-inferiority trial evaluated 540 eligible adult patients randomly assigned (2:1) to the intervention (20 mg/kg FospropofolFD) or control (2 mg/kg propofol-MCT/LCT) groups. Main Outcome Measure: The primary efficacy endpoint was the success rate, defined as a Modified Observer's Assessment of Alertness/Sedation Scale score of 1 within 5 min after study drug administration. The safety endpoints consisted of adverse events (AEs) related to consciousness, cognitive function, hemodynamic status, liver and kidney function, and blood tests. Results: A total of 347 (96.3%) and 175 (97.2%) patients in the intervention and control groups, respectively, completed the study. The success rate for the primary outcome was 97.7% for both study drugs. The most frequent AEs in the intervention group were abnormal feeling (62.0%), blood pressure reduction (13.5%), and injection site pain (13.3%). No AEs related to consciousness and mental and cognitive functions or serious adverse events were reported. Conclusion: FospropofolFD (20 mg/kg) is not inferior to propofol-MCT/LCT (2 mg/kg) in general anesthesia induction for American Society of Anesthesiologists (ASA) physical status I-II adult patients undergoing elective surgeries. It is safe and effective for clinical use under anesthesiologist monitoring. Impact on Practice Statement: FospropofolFD can produce a general anesthesia effect and reduce the incidence of pain at the site of injection.

Pharmacokinetic and pharmacodynamic properties of ciprofol emulsion in Chinese subjects: a single center, open-label, single-arm dose-escalation phase 1 study.

We conducted a single-center, single-arm, open-label, dose-escalation phase 1 clinical trial to evaluate the tolerability of a single intravenous injection of ciprofol emulsion for the induction of short-term general anesthesia. Four doses of ciprofol (0.15 mg/kg, n = 2; 0.4 mg/kg, n = 10; 0.6 mg/kg, n = 6; 0.9 mg/kg, n = 6) were administered. Twenty-four subjects were enrolled, with 18 subjects in the 0.4 to 0.9 mg/kg dosage groups included in the data analysis. In total, 37 mild and 4 moderate adverse events (AEs), including 9 abnormal limb movements (3 moderate cases), 8 cases of sinus bradycardia, 11 cases of prolonged QTcF interval (including 1 moderate case), and 1 case of hypotension, were found, but no serious AEs were reported. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores rapidly decreased after ciprofol administration. The duration of recovery of the verbal response, loss of verbal response duration, the duration of MOAA/S ≤1 and the duration until the return of responsiveness were all increased in a dose-dependent manner. The durations of bispectral index values <60 (6, 8 and 12 min) were similar to the durations of loss of verbal response (6, 8 and 14 min) and MOAA/S ≤1 (5, 5.5 and 13.5 min) in the 0.4, 0.6 and 0.9 mg/kg dose groups, respectively. The plasma concentration reached a peak value approximately 2 min after injection in the 0.4-0.9 mg/kg groups and all subjects fully recovered after ciprofol administration, with the shortest time being 9.2 min in the 0.4 mg/kg group. A ciprofol dosing regimen of 0.4-0.9 mg/kg was well-tolerated and exhibited rapid onset and recovery properties.

Genetic structure, gene flow pattern, and association analysis of superior germplasm resources in domesticated upland cotton (Gossypium hirsutum L.).

Gene flow patterns and the genetic structure of domesticated crops like cotton are not well understood. Furthermore, marker-assisted breeding of cotton has lagged far behind that of other major crops because the loci associated with cotton traits such as fiber yield and quality have scarcely been identified. In this study, we used 19 microsatellites to first determine the population genetic structure and patterns of gene flow of superior germplasm resources in upland cotton. We then used association analysis to identify which markers were associated with 15 agronomic traits (including ten yield and five fiber quality traits). The results showed that the upland cotton accessions have low levels of genetic diversity (polymorphism information content = 0.427), although extensive gene flow occurred among different ecological and geographic regions. Bayesian clustering analysis indicated that the cotton resources used in this study did not belong to obvious geographic populations, which may be the consequence of a single source of domestication followed by frequent genetic introgression mediated by human transference. A total of 82 maker-trait associations were examined in association analysis and the related ratios for phenotypic variations ranged from 3.04% to 47.14%. Interestingly, nine SSR markers were detected in more than one environmental condition. In addition, 14 SSR markers were co-associated with two or more different traits. It was noteworthy that NAU4860 and NAU5077 markers detected at least in two environments were simultaneously associated with three fiber quality traits (uniformity index, specific breaking strength and micronaire value). In conclusion, these findings provide new insights into the population structure and genetic exchange pattern of cultivated cotton accessions. The quantitative trait loci of domesticated cotton identified will also be very useful for improvement of yield and fiber quality of cotton in molecular breeding programs.

Piceatannol inhibits proliferation and induces apoptosis of bladder cancer cells through regulation of the PTEN/AKT signal pathway.

This study was aimed to investigate the effect of piceatannol (PIC) on the proliferation and apoptosis of bladder cancer cell line EJ, and the underlying mechanism.   Bladder cancer cell line EJ was incubated with different concentrations of PIC, and CCK-8 method was used to determine the effect of the treatment on cell proliferation. The effect of PIC on cell cycle, apoptosis and the expressions of related signal pathway proteins were determined using Western blotting. Flow cytometry showed that PIC inhibited the proliferation of EJ cells in a concentration- and time-dependent fashion. Moreover, EJ cells were significantly blocked in G0/G1 phase, when compared with the blank control group (p < 0.05). In addition, PIC enhanced apoptosis of EJ cells in a concentration-dependent manner (p < 0.05). Results from western blotting showed that, compared with the control group, PIC upregulated the protein expression of PTEN, but downregulated Akt protein phosphorylation, relative to control cells. PIC significantly inhibits the proliferation of EJ cells and enhances their apoptosis through a mechanism related to the activation of PTEN/Akt signaling pathway.

The preclinical pharmacological study on HX0969W, a novel water-soluble pro-drug of propofol, in rats.

BACKGROUND: Propofol is the most widely used intravenous sedative-hypnotic anesthetic in clinical practice. However, many serious side effects have been related to its lipid emulsion formulation. The pro-drug design approach was used to develop the water-soluble propofol, which could effectively resolve the limitations associated with the lipid emulsion formulation. Thus, the new water-soluble pro-drug of propofol, HX0969W, was designed and synthesized. The objective of this study was to conduct preclinical pharmacological studies on this novel water-soluble pro-drug of propofol. METHODS: The assessment of the loss of the righting reflex (LoRR) was used for the pharmacodynamic study, and liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography- fluorescence were used for the pharmacokinetic study. RESULTS: The potency of HX0969W (ED50 [95% CI], 46.49 [43.89-49.29] mg/kg) was similar to that of fospropofol disodium (43.66 [43.57-43.75] mg/kg), but was lower than that of propofol (4.82 [4.8-14.82] mg/kg). Administered with a dose of 2-fold ED50, propofol required a shorter time to cause LoRR than that of HX0969W and fospropofol. However, the LoRR duration was significantly longer in response to the administration of HX0969W and fospropofol disodium than that caused by propofol. In the pharmacokinetic study, the Cmax of fospropofol was higher than that of HX0969W. HX0969W had a shorter mean residual time and a rapid clearance rate than that of fospropofol disodium. There was no significant difference between the Tmax of the propofol whether it was released by HX0969W or fospropofol disodium; the Cmax of propofol released by HX0969W was similar to that of propofol, which was higher than the propofol released by fospropofol disodium.

Metabolite identification, tissue distribution, excretion and preclinical pharmacokinetic studies of ET-26-HCl, a new analogue of etomidate.

ET-26-HCl, a novel anaesthetic agent with promising pharmacological properties, lacks extensive studies on pharmacokinetics and disposition in vitro and in vivo. In this study, we investigated the metabolic stability, metabolite production and plasma protein binding (PPB) of ET-26-HCl along with its tissue distribution, excretion and pharmacokinetics in animals after intravenous administration. Ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry identified a total of eight new metabolites after ET-26-HCl biotransformation in liver microsomes from different species. A hypothetical cytochrome P450-metabolic pathway including dehydrogenation, hydroxylation and demethylation was proposed. The PPB rate was highest in mouse and lowest in human. After intravenous administration, ET-26-HCl distributed rapidly to all tissues in rats and beagle dogs, with the highest concentrations in fat and liver. High concentrations of ET-26-acid, a major hydroxylation metabolite of ET-26-HCl, were found in liver, plasma and kidney. Almost complete clearance of ET-26-HCl from plasma occurred within 4 h after administration. Only a small fraction of the parent compound and its acid form were excreted via the urine and faeces. Taken together, the results added to a better understanding of the metabolic and pharmacokinetic properties of ET-26-HCl, which may contribute to the further development of this drug.

Developing a Novel Nanoscale Porphyrinic Metal-Organic Framework: A Bifunctional Platform with Sensitive Fluorescent Detection and Elimination of Nitenpyram in Agricultural Environment.

Developing a rapid sensing platform with effective pesticide degradation capabilities integrated into a single structure and realistic application is an imminent challenge to ensure sustainable agriculture and food safety. Here, we described establishment of a bifunctional nanoscale porphyrinic metal-organic framework (MOF) probe serving as a sensor for detection of trace nitenpyram and as a photocatalyst to facilitate the pesticide degradation. Based on the signal turned "on-off", the strong fluorescence of the probe was quenched by the target, leading to the sensing range from 0.05 to 10.0 µg mL-1 and a detection limit of 0.03 µg mL-1. Given the versatile design by which the porphyrin photosensitizers were isolated subtly in the MOF to avoid self-quenching, the probe was endowed with sustainable and efficient pesticide photodegradation activity with a degradation rate of ∼95% for nitenpyram. Our work represents powerful all-in-one MOF-derived materials jointly for sensing and degrading pesticide residues in agricultural soils and other pesticide-contaminated environments.

Effect of volatile anesthetics on mortality and clinical outcomes in patients undergoing coronary artery bypass grafting: a meta-analysis of randomized clinical trials.

INTRODUCTION: It remains unclear whether intraoperative use of volatile anesthetics has a positive effect on postoperative clinical outcomes in patients undergoing coronary artery bypass grafting (CABG). Therefore, we aimed to systematically analyze the long- and short-term mortality rates and the clinical outcomes of volatile anesthesia compared to those of total intravenous anesthesia (TIVA) in patients undergoing CABG. EVIDENCE ACQUISITION: We queried the MEDLINE, Embase, and CENTRAL databases from inception to October 2019 for relevant randomized clinical trials (RCTs) on the intraoperative use of volatile anesthetics in patients undergoing CABG. EVIDENCE SYNTHESIS: We pooled and analyzed 36 eligible RCTs with 10,308 patients and found that there was no significant difference in the long- and short-term mortality rate between the use of volatile anesthesia and TIVA during CABG. 30-day mortality, volatile group (39/2,824, 1.4%) vs. TIVA group (35/2,786, 1.3%), RR=1.11, 95% CI [0.70, 1.74], P value for effect =0.66, I2=0%, moderate-certainty evidence; One-year mortality, volatile group (77/2,749, 2.8%) vs. TIVA group (78/2,731, 2.9%), RR=0.98, 95% CI [0.72, 1.34], P value for effect =0.90, I2=0%, moderate-certainty evidence. Mechanical ventilation time was reduced in volatile group (MD -0.65, 95% CI [-1.07, -0.24], P value for effect =0.002, I2=26%). CONCLUSIONS: There is no difference in the long- and short-term mortality and clinical outcomes between intraoperative use of volatile anesthetics and TIVA during CABG. However, volatile anesthetics may shorten the mechanical ventilation time. There is a need for high-quality multicenter RCTs that specifically assess factors that influence mortality and clinical outcomes.

Copper ion modified graphitic C3N4 nanosheets enhanced luminol-H2O2 chemiluminescence system: Toward highly selective and sensitive bioassay of H2S in human plasma.

A high-efficient chemiluminescence (CL) platform for highly selective and sensitive H2S detection was constructed on the basis of the quenching effect of S2- on the copper ion modified graphitic carbon nitride nanosheets (Cu2+-g-C3N4 NSs) enhanced luminol-H2O2 system. Cu2+-g-C3N4 NSs with horseradish peroxidase-like catalytic activity were prepared and provide a great improvement for luminol-H2O2 system. The presence of S2- induced the formation of CuS precipitate on g-C3N4 NSs surface. The precipitate can block the catalytic Cu2+ sites on the g-C3N4 NSs surface, resulting in a great CL decrease of CL system. Based on such a mechanism, a simple, highly selective and sensitive CL biosensor for H2S detection was designed. Under the optimized conditions, luminol-H2O2-Cu2+-g-C3N4 NSs system gave a decrease of CL intensity with the Na2S concentration increasing. The CL biosensor is in a linear range of 10.0 pM-50.0 nM and the detection limit for detecting Na2S is as low as 2.0 pM. Moreover, the method here has enjoyed a successful application for determining H2S in human plasma samples and the recovery is between 95.7% and 110.0%.