Engineered Cell Membrane-Coated Nanoparticles: New Strategies in Glioma Targeted Therapy and Immune Modulation.

Gliomas, the most prevalent primary brain tumors, pose considerable challenges due to their heterogeneity, intricate tumor microenvironment (TME), and blood-brain barrier (BBB), which restrict the effectiveness of traditional treatments like surgery and chemotherapy. This review provides an overview of engineered cell membrane technologies in glioma therapy, with a specific emphasis on targeted drug delivery and modulation of the immune microenvironment. This study investigates the progress in engineered cell membranes, encompassing physical, chemical, and genetic alterations, to improve drug delivery across the BBB and effectively target gliomas. The examination focuses on the interaction of engineered cell membrane-coated nanoparticles (ECM-NPs) with the TME in gliomas, emphasizing their potential to modulate glioma cell behavior and TME to enhance therapeutic efficacy. The review further explores the involvement of ECM-NPs in immunomodulation techniques, highlighting their impact on immune reactions. While facing obstacles related to membrane stability and manufacturing scalability, the review outlines forthcoming research directions focused on enhancing membrane performance. This review underscores the promise of ECM-NPs in surpassing conventional therapeutic constraints, proposing novel approaches for efficacious glioma treatment.

Erector spinae plane block versus quadratus lumborum block for postoperative analgesia after laparoscopic nephrectomy: A randomized controlled trial.

STUDY OBJECTIVE: We compared the analgesic effects of erector spinae plane block versus quadratus lumborum block following laparoscopic nephrectomy. DESIGN: A randomized controlled trial. SETTING: A tertiary hospital in Beijing, China. PATIENTS: Patients scheduled for elective laparoscopic nephrectomy. INTERVENTIONS: A total of 110 patients were enrolled and randomized to receive either erector spinae plane block (n = 55) or quadratus lumborum block (n = 55) under ultrasound guidance. Patient-controlled sufentanil analgesia was provided after surgery. MEASUREMENTS: Our primary outcome was cumulative opioid consumption within 24 h after surgery. Secondary outcomes included postoperative pain intensity, subjective sleep quality, and quality of recovery. MAIN RESULTS: All 110 patients (mean 53 years, 57.3% female) were included in the intention-to-treat analysis. Cumulative sufentanil equivalent within 24 h was lower in patients given erector spinae plane block (median 13 µg, interquartile range 4 to 33) than in those given quadratus lumborum block (median 25 µg, interquartile range 13 to 39; median difference - 8 µg, 95% CI -15 to 0, P = 0.041). Pain intensity (0-10 range where 0 = no pain and 10 = the worst pain) at 2, 6, 12, and 24 h after surgery was lower with erector spinae plane block (at rest: median differences -1 point, all P ≤ 0.009; with movement: median differences -2 to -1 points, all P < 0.001). Subjective sleep quality on the night of surgery (the Richards-Campbell Sleep Questionnaire: 0-100 range, higher score better; median difference 12, 95% CI 2 to 23, P = 0.018) and quality of recovery at 24 h (the Quality of Recovery-15: 0-150 range, higher score better; median difference 8, 95% CI 2 to 15, P = 0.012) were better with erector spinae plane block. No procedure-related adverse events occurred. CONCLUSIONS: Compared with quadratus lumborum block, erector spinae plane block provided better analgesia as manifested by lower opioid consumption and pain intensity for up to 24 h after laparoscopic nephrectomy.

Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline.

Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood-brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.

Exploring the potential of white birch sap: A natural alternative to traditional skin whitening agents with reduced side effects.

Common tyrosinase (TYR) inhibitors used in cosmetics, such as hydroquinone, kojic acid, and arbutin, can cause side effects including erythema, skin peeling, and dryness. Therefore, the development of natural whitening agents that offer excellent permeability, minimal irritation, and high safety has become a primary focus in the field of TYR inhibitors. In this study, we demonstrate that White birch sap (WBS), within a safe concentration range, effectively reduces TYR activity and melanin content in both B16F10 mouse melanoma cells and zebrafish larvae. Importantly, WBS exhibits minimal irritation to neutrophils in fluorescent zebrafish and does not affect the behavior of adult zebrafish. Furthermore, WBS downregulates the gene expression levels of microphthalmia-associated transcription factor, TYR, tyrosinase-related protein-1, and tyrosinase-related protein-2 in B16F10 cells. In conclusion, our research confirms that WBS, a naturally derived substance, offers high safety and mild effects, making it a promising candidate for a skin-whitening agent.

Multimodal prevention of emergence cough following nasal endoscopic surgery under general anesthesia: a double-blind randomized trial.

Purpose: Cough during emergence from anesthesia is a common problem and may cause adverse events. Monotherapy faces uncertainty in preventing emergence cough due to individual differences. We aimed to evaluate the efficacy and safety of multimodal intervention for preventing emergence cough in patients following nasal endoscopic surgery. Methods: In this double-blind randomized trial, 150 adult patients undergoing nasal endoscopic surgery were randomly allocated into three groups. For the control group (n = 50), anesthesia was performed according to clinical routine, no intervention was provided. For the double intervention group (n = 50), normal saline 3 mL was sprayed endotracheally before intubation, 0.4 µg/kg dexmedetomidine was infused over 10 min after intubation, and target-controlled remifentanil infusion was maintained at an effect-site concentration of 1.5 ng/mL before extubation after surgery. For the multimodal intervention group (n = 50), 0.5% ropivacaine 3 mL was sprayed endotracheally before intubation, dexmedetomidine and remifentanil were administered as those in the double intervention group. The primary endpoint was the incidence of emergence cough, defined as single cough or more from end of surgery to 5 min after extubation. Results: The incidences of emergence cough were 98% (49/50) in the control group, 90% (45/50) in the double group, and 70% (35/50) in the multimodal group, respectively. The incidence was significantly lower in the multimodal group than those in the control (relative risk 0.71; 95% CI 0.59 to 0.86; p < 0.001) and double (relative risk 0.78; 95% CI 0.63 to 0.95; p = 0.012) groups; the difference between the double and control groups was not statistically significant (relative risk 0.92; 95% CI 0.83 to 1.02; p = 0.20). The severity of sore throat was significantly lower in the multimodal group than that in the control group (median difference-1; 95% CI -2 to 0; p = 0.016). Adverse events did not differ among the three groups. Conclusion: For adult patients undergoing endonasal surgery, multimodal intervention including ropivacaine topical anesthesia before intubation, dexmedetomidine administration after intubation, and remifentanil infusion before extubation after surgery significantly reduced emergence cough and was safe.

Microbial metabolite trimethylamine-N-oxide induces intestinal carcinogenesis through inhibiting farnesoid X receptor signaling.

PURPOSE: Microbial dysbiosis is considered as a hallmark of colorectal cancer (CRC). Trimethylamine-N-oxide (TMAO) as a gut microbiota-dependent metabolite has recently been implicated in CRC development. Nevertheless, evidence relating TMAO to intestinal carcinogenesis remains largely unexplored. Herein, we aimed to examine the crucial role of TMAO in CRC progression. METHODS: Apcmin/+ mice were treated with TMAO or sterile PBS for 14 weeks. Intestinal tissues were isolated to evaluate the effects of TMAO on the malignant transformation of intestinal adenoma. The gut microbiota of mouse feces was detected by 16S rRNA sequencing analysis. HCT-116 cells were used to provide further evidence of TMAO on the progression of CRC. RESULTS: TMAO administration increased tumor cell and stem cell proliferation, and decreased apoptosis, accompanied by DNA damage and gut barrier impairment. Gut microbiota analysis revealed that TMAO induced changes in the intestinal microbial community structure, manifested as reduced beneficial bacteria. Mechanistically, TMAO bound to farnesoid X receptor (FXR), thereby inhibiting the FXR-fibroblast growth factor 15 (FGF15) axis and activating the Wnt/ß-catenin signaling pathway, whereas the FXR agonist GW4064 could blunt TMAO-induced Wnt/ß-catenin pathway activation. CONCLUSION: The microbial metabolite TMAO can enhance intestinal carcinogenesis by inhibiting the FXR-FGF15 pathway.

Experimental study of energy­absorbing and support characteristics of glass microsphere-filled steel tube columns under uniaxial compression.

An innovative energy-absorbing and bearing structure was proposed, which incorporated the coupling of glass microspheres with a metal tube. Glass microsphere-filled steel tube (GMFST) column, consisting of external steel tube and inner glass microspheres, was expected to give full play to the energy-absorbing and load-bearing capacities of the particle while restricting particle flow from collapsing, thereby enhancing the overall structural strength. Four groups of steel tubes and the GMFST specimens were designed and subjected to axial compression tests at four different loading rates to investigate the performance of the structure. These tests aimed to analyze the deformation mode, mechanical response, and energy absorption capacity of the GMFST columns under quasi-static to low-speed compression conditions. The results indicated that the deformation process and failure mode of GMFST columns were similar to those of hollow steel tubes, albeit with a different post-buckling mode. Filling the steel tubes with glass microspheres reduced the load fluctuation range, moderated load-displacement curves, and exhibited a strain rate strengthening effect. The GMFST columns demonstrated superior energy absorption capacity, with significant increases in crush force efficiency, the averaged crush force, and the total absorbed energy, particularly in terms of subsequent support capacity. The load-increasing reinforcement properties enabled GMFST columns to overcome the limitations associated with the unstable post-buckling path of energy­absorbing damping structure, exhibiting outstanding load-bearing performance and stability in the later stages. The results provided valuable guidelines for designing and engineering high-performance GMFST columns, serving as a new type of energy-absorbing and supporting structure.

Osteosarcoma Cells Secrete CXCL14 That Activates Integrin α11ß1 on Fibroblasts to Form a Lung Metastatic Niche.

Cooperation between primary malignant cells and stromal cells can mediate the establishment of lung metastatic niches. Here, we characterized the landscape of cell populations in the tumor microenvironment in treatment-naïve osteosarcoma using single-cell RNA sequencing and identified a stem cell-like cluster with tumor cell-initiating properties and prometastatic traits. CXCL14 was specifically enriched in the stem cell-like cluster and was also significantly upregulated in lung metastases compared with primary tumors. CXCL14 induced stromal reprogramming and evoked a malignant phenotype in fibroblasts to form a supportive lung metastatic niche. Binding of CXCL14 to heterodimeric integrin α11ß1 on fibroblasts activated actomyosin contractility and matrix remodeling properties. CXCL14-stimulated fibroblasts produced TGFß and increased osteosarcoma invasion and migration. mAbs targeting the CXCL14-integrin α11ß1 axis inhibited fibroblast TGFß production, enhanced CD8+ T cell-mediated antitumor immunity, and suppressed osteosarcoma lung metastasis. Taken together, these findings identify cross-talk between osteosarcoma cells and fibroblasts that promotes metastasis and demonstrate that targeting the CXCL14-integrin α11ß1 axis is a potential strategy to inhibit osteosarcoma lung metastasis. SIGNIFICANCE: Cooperation between stem-like osteosarcoma cells and fibroblasts mediated by a CXCL14-integrin α11ß1 axis creates a tumor-supportive lung metastatic niche and represents a therapeutic target to suppress osteosarcoma metastasis.

Cnidium officinale Makino: Phytology, Phytochemistry, Toxicology, Pharmacology and Prescriptions (1967-2023).

Cnidium officinale Makino (COM), a perennial herbaceous plant in the Apiaceous family, widely distribute in Eastern Asia and Asia-Temperate. It has a long history application as a traditional medicine for invigorating the blood and removing blood stasis, and also has been employed to diet, pesticide, herbal bathing materials, the cosmetic and skin care industry. However, there has been no associated review of literature in the past half a century (1967-2023). By searching the international authoritative databases and collecting 229 literatures closely related to COM, herewith a comprehensive and systematic review was conducted. The phytology includes plant distribution and botanical characteristics. The phytochemistry covers 8 major categories, 208 compounds in total, and the quantitative determination of 14 monomer compounds, total polyphenols and total flavonoids. The clinical trial in pregnant women and toxic experiments in mice, the pharmacology of 7 aspects and 82 frequently used prescriptions are summarized. It is expected that this paper will provide forward-looking scientific thinking and literature support for the further modern research, development and utilization of COM.

Chemical substances and their activities in sea cucumber Apostichopus japonicus: A review.

Apostichopus japonicus, also known as Stichopus japonicus, with medicinal and food homologous figures, is a globally recognized precious ingredient with extremely high nutritional value. There is no relevant review available through literature search, so this article selects the research articles through the keywords "sea cucumber" and "Apostichopus japonicus (Stichopus japonicus)" in six professional databases, such as Wiley, PubMed, ScienceDirect, ACS, Springer, and Web of Science, from 2000 to the present, summarizing the extraction, isolation, and purification methods for the four major categories (polysaccharides, proteins and peptides, saponins, and other components) of the A. japonicus chemical substances and 10 effective biological activities of A. japonicus. Included are anticoagulation, anticancer/antitumor activities, hematopoiesis, regulation of gut microbiota, and immune regulatory activities that correspond to traditional efficacy. Literature support is provided for the development of medicines and functional foods and related aspects that play a leading role in future directions.

Determination of multi-mycotoxins in vegetable oil via liquid chromatography-high resolution mass spectrometry assisted by a complementary liquid-liquid extraction.

The simultaneous determination of multi-mycotoxins in food commodities are highly desirable due to their potential toxic effects and mass consumption of foods. Herein, liquid chromatography-quadrupole exactive orbitrap mass spectrometry was proposed to analyze multi-mycotoxins in commercial vegetable oils. Specifically, the method featured a successive liquid-liquid extraction process, in which the complementary solvents consisted of acetonitrile and water were optimized. Resultantly, matrix effects were reduced greatly. External calibration approach revealed good quantification property for each analyte. Under optimal conditions, the recovery ranging from 80.8% to 109.7%, relative standard deviation less than 11.7%, and good limit of quantification (0.35 to 45.4 ng/g) were achieved. The high accuracy of proposed method was also validated. The detection of 20 commercial vegetable oils revealed that aflatoxins B1 and B2, zearalenone were observed in 10 real samples. The as-developed method is simple and low-cost, which merits the wide applications for scanning mycotoxins in oil matrices.

[Determination of 22 mycotoxins in milk by liquid chromatography-quadrupole/orbitrap mass spectrometry].

Mycotoxins have carcinogenic, mutagenic, hepatotoxic, nephrotoxic, immunotoxic, neurotoxic, and teratogenic properties. Thus, these substances have attracted significant attention because they pose a threat to human health. As research on mycotoxins deepens, new structural analogues of mycotoxins are constantly being discovered. In this study, a method based on high performance liquid chromatography-quadrupole/orbitrap mass spectrometry was established for the simultaneous determination of 22 mycotoxins in milk. A simple, effective, and rapid pretreatment method was optimized by focusing on the solvent type, extractant volume, and extracting salt based on the characteristics of the mycotoxins and sample matrix. The analytes were extracted using 0.5% formic acid acetonitrile solution and added with sodium chloride to separate fats from water. The samples were centrifuged at 8000 r/min (4 ℃) for 5 min using a centrifuge and then concentrated using nitrogen. The dry residue was dissolved with 50% methanol aqueous solution. Twenty-two mycotoxins were separated on a ZORBAX Eclipse Plus C18 chromatographic column (100 mm×2.1 mm, 1.7 µm), and quantitative analysis was performed using the isotope internal standard method. The analytes were determined by liquid chromatography-quadrupole/orbitrap mass spectrometry in positive electrospray ionization mode. Qualitative analyses of the compounds were performed in full mass spectrometry/data-dependent tandem mass spectrometry (MS/dd-MS2) mode. Good linearities in the range of 0.5-100.0 µg/L were observed for the 22 mycotoxins, and the correlation coefficients (R2) were greater than 0.999. The limits of detection (S/N=3) and quantification (S/N=10) ranged from 0.3 to 0.5 µg/kg and from 1.0 to 1.5 µg/kg, respectively. The average recoveries of the 22 mycotoxins at three spiked levels of 1.5, 5.0, and 15 µg/kg were between 84.7% and 100.8%, with relative standard deviations (RSDs) of 1.2%-9.9%. These findings indicate that the method has high sensitivity and accuracy as well as good precision. Finally, the method was applied to the detection and analysis of mycotoxins in 25 actual commercial milk samples. The results revealed that the selected samples were not contaminated with any of the mycotoxins analyzed. Thus, the proposed method is useful as a quick preprocessing and confirmatory method for the simultaneous determination of mycotoxins in milk.

Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.

Kalopanax septemlobus: its phytochemistry, pharmacology and toxicity (1966-2022).

Kalopanax septemlobus is a traditional herbal medicine for multiple medicinal sites (root, stem bark, bark, leaves) in East Asia, and its bark has a significant curative effect on rheumatoid arthritis. In the past 13 years (2009-2022), the research literature accounted for 50% of the total, and it is becoming a research highlight of the relevant international scholars (ACS, ScienceDirect, PubMed, Springer, and Web of Science). This paper is the first comprehensive review of its chemistry, pharmacology, and toxicity for more than half a century (1966-2022), in which the chemical studies include triterpenoids & saponins (86 compounds), and phenylpropanoids (26 compounds), involving 46 new structures and one biomarker-triterpenoid saponin (Kalopanaxsaponin A); According to the number of literature, the pharmacological effects and mechanisms are systematically divided into five aspects, such as: anti-inflammatory, anti-tumor, antioxidant, antifungal and anti-diabetic, etc., covering its toxicological progress. To provide literature support for the exploration of new drugs against related diseases, such as rheumatoid arthritis, which are becoming younger nowadays.

Mini-dose esketamine-dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial.

BACKGROUND: Patients often experience severe pain after scoliosis correction surgery. Esketamine and dexmedetomidine each improves analgesia but can produce side-effects. We therefore tested the hypothesis that a mini-dose esketamine-dexmedetomidine combination safely improves analgesia. METHODS: Two hundred male and female adults having scoliosis correction surgery were randomised to patient-controlled sufentanil analgesia (4 µg kg-1 in normal saline) with either a combined supplement (esketamine 0.25 mg ml-1 and dexmedetomidine 1 µg ml-1) or placebo. The primary outcome was the incidence of moderate-to-severe pain within 72 h, defined as a numeric rating scale (NRS: 0=no pain and 10=worst pain) score ≥4 at any of seven time points. Amongst secondary outcomes, subjective sleep quality was assessed with an NRS score (0=best sleep and 10=worst sleep) for the first five postoperative nights. RESULTS: There were 199 subjects included in the intention-to-treat analysis. Mean infusion rates were 5.5 µg kg-1 h-1 for esketamine and 0.02 µg kg-1 h-1 for dexmedetomidine. The primary outcome incidence was lower with the combined supplement (65.7% [65/99]) than with placebo (86.0% [86/100]; relative risk 0.76; 95% confidence interval: 0.65-0.90; P=0.001). Subjects given the combined supplement had lower pain intensity at rest at five time points (median difference -1 point; P≤0.005), lower pain intensity with movement at six time points (median difference -1 point; P≤0.001), and better subjective sleep quality for the first 5 postoperative nights (median difference -2 to -1 points; P<0.001). Adverse events did not differ between groups. CONCLUSIONS: The mini-dose esketamine-dexmedetomidine combination safely improved analgesia and subjective sleep quality after scoliosis correction surgery. CLINICAL TRIAL REGISTRATION: NCT04791059.

Advances in Antioxidant Applications for Combating 131I Side Effects in Thyroid Cancer Treatment.

Thyroid cancer is the most common endocrine cancer, and its prevalence has been increasing for decades. Approx. 95% of differentiated thyroid carcinomas are treated using 131iodine (131I), a radionuclide with a half-life of 8 days, to achieve optimal thyroid residual ablation following thyroidectomy. However, while 131I is highly enriched in eliminating thyroid tissue, it can also retain and damage other body parts (salivary glands, liver, etc.) without selectivity, and even trigger salivary gland dysfunction, secondary cancer, and other side effects. A significant amount of data suggests that the primary mechanism for these side effects is the excessive production of reactive oxygen species, causing a severe imbalance of oxidant/antioxidant in the cellular components, resulting in secondary DNA damage and abnormal vascular permeability. Antioxidants are substances that are capable of binding free radicals and reducing or preventing the oxidation of the substrate in a significant way. These compounds can help prevent damage caused by free radicals, which can attack lipids, protein amino acids, polyunsaturated fatty acids, and double bonds of DNA bases. Based on this, the rational utilization of the free radical scavenging function of antioxidants to maximize a reduction in 131I side effects is a promising medical strategy. This review provides an overview of the side effects of 131I, the mechanisms by which 131I causes oxidative stress-mediated damage, and the potential of natural and synthetic antioxidants in ameliorating the side effects of 131I. Finally, the disadvantages of the clinical application of antioxidants and their improving strategies are prospected. Clinicians and nursing staff can use this information to alleviate 131I side effects in the future, both effectively and reasonably.

Optimal strategy for delirium detection in older patients admitted to intensive care unit after non-cardiac surgery.

Background: Delirium detection is challenging due to the fluctuating nature and frequent hypoactive presentation. This study aimed to determine an optimal strategy that detects delirium with higher sensitivity but lower effort in older patients admitted to the intensive care unit (ICU) after surgery. Methods: This was a secondary analysis of the database from a randomized trial. Seven hundred older patients (aged ≥65 years) who were admitted to the ICU after elective noncardiac surgery were enrolled. Delirium was assessed with the Confusion Assessment Method for the ICU (CAM-ICU) twice daily during the first 7 days postoperatively. The sensitivity of different strategies in detecting delirium were analyzed and compared. Results: Of all enrolled patients, 111 (15.9%; 95% CI: 13.3% to 18.8%) developed at least one episode of delirium during the first 7 postoperative days. Among patients who developed delirium, 60.4% (67/111) had their first delirium onset on postoperative day 1, 84.7% (94/111) by the end of day 2, 91.9% (102/111) by the end of day 3, and 99.1% (110/111) by the end of day 4. Compared with delirium assessment twice daily for 7 days, twice-daily measurements for 5 days detected 100% of delirium patients with 71% efforts; twice-daily measurements for 4 days detected 99% (95% CI: 94% to 100%) of delirium patients with 57% efforts; twice-daily assessment for 3 days detected 92% (95% CI: 85% to 96%) of delirium patients with only 43% efforts. Conclusions: For older patients admitted to the ICU after elective noncardiac surgery, it is reasonable to detect delirium with the CAM-ICU twice daily for no more than 5 days, and if the personnel and funds are insufficient, 4 days could be sufficient.

Comparison of two frailty indices in predicting life-threatening morbidity and mortality among older patients undergoing elective high-risk abdominal surgery.

Background: Frailty predicts an increased risk of postoperative morbidity and mortality. Comparison of the predictive performance between two deficit accumulation models of frailty, the modified frailty index (mFI) and the revised-Risk Analysis Index (RAI-rev), is poorly understood. This study compared the predictive abilities of the above two frailty indices in predicting life-threatening morbidity and mortality among older patients following elective high-risk abdominal surgery. Methods: This retrospective cohort study extracted perioperative data of older patients (age ≥65 years) undergoing elective high-risk abdominal surgery at a single institution between January 2018 and December 2020. Preoperative frailty was screened by mFI and RAI-rev scoring systems. The primary outcome was the composite of postoperative life-threatening morbidity and mortality during hospitalization. Multivariable logistic regression analyses were performed to investigate the association of the two frailty indices with the primary outcome. Receiver-operating characteristic (ROC) curve was employed to test the predictive performances of the two frailty instruments in predicting the composite primary outcome. The difference between the area under the curves (AUCs) was assessed by DeLong's test. Results: 1,132 older patients (mean age, 73.4 ± 6.2 years; 63.9% male) were included. Of these, 107 (9.5%) developed postoperative life-threatening morbidity and mortality. In multivariable logistic regression analyses, rising continuous frailty scores (mFI: adjusted OR 1.319 per 0.09-point increase in score, 95% CI 1.151-1.511, p < 0.001; RAI-rev: adjusted OR 1.052 per 1-point increase in score, 95% CI 1.018-1.087, p = 0.002) as well as dichotomized frailty measures (mFI ≥0.27: adjusted OR 2.059, 95% CI 1.328-3.193, p = 0.001; RAI-rev ≥45: adjusted OR 1.862, 95% CI 1.188-2.919, p = 0.007) were associated with increased odds of the primary outcome separately. ROC curve analysis showed that the discrimination of mFI and RAI-rev scores for the life-threatening morbidity and mortality was poor and comparable (AUC: 0.598 [95% CI 0.569-0.627] vs. 0.613 [95% CI 0.583-0.641]; DeLong's test: Z = 0.375, p = 0.7075). Conclusion: High mFI and RAI-rev scores were associated with an increased risk of life-threatening morbidity and mortality in older patients undergoing elective high-risk abdominal surgery. However, both frailty indices displayed poor discrimination for postoperative life-threatening morbidity and mortality.