Relationship between age and remimazolam dose required for inducing loss of consciousness in older surgical patients.

Background: Remimazolam is a new ultra-short-acting benzodiazepine for procedural sedation and general anaesthesia, characterised by rapid onset of action, quick recovery, and organ-independent metabolism. Older patients tend to sustain more treatment-emergent adverse events (TEAEs) and worse perioperative prognoses after receiving remimazolam. However, few studies have investigated the appropriate dose of remimazolam for loss of consciousness (LOC) in geriatric patients. We designed this study to provide evidence for dose references and elucidate the relationship between age and remimazolam requirement for inducing LOC during anaesthesia induction. Methods: Exactly 120 patients scheduled for general surgery under general anaesthesia were included and divided into two groups: Group A (60 patients, 18-64 years) and Group B (60 patients, ≥ 65 years). LOC, defined as a Modified Observer's Assessment of Alertness and Sedation score at 1 had been reached, emerged after all participants received a continuous infusion of remimazolam at a rate of 0.05 mg/kg/min. Results: The remimazolam required for inducing LOC was 0.26 and 0.19 mg/kg in groups A and B, respectively, and the remimazolam dose in group B decreased by 26.9% compared to group A. According to the bivariate linear correlation analysis, remimazolam requirement was negatively correlated with age. Multivariable linear regression models and further adjustments for potential impact factors indicated that age was an independent factor for the remimazolam dose required for LOC. Conclusion: This study demonstrated that age was significantly and independently correlated with the remimazolam requirement for inducing LOC. To obtain haemodynamic stability during the induction of general anaesthesia, appropriately reducing the remimazolam dose is recommended for geriatric patients.

Clinical value of the expression levels of tumor protein D52 and miR-133a on prognosis assessment of pancreatic cancer surgery.

Objective: To investigate the clinical value of the expression levels of tumor protein D52 (TPD52) and miR-133a on the prognosis assessment of pancreatic cancer surgery. Methods: This was a retrospective study. Ninety-seven patients who underwent radical surgery for pancreatic cancer in Cangzhou Central Hospital from January 2018 to January 2022 were selected and divided into four groups: TPD52 high expression group, TPD52 low expression group, miR-133a high expression group and miR-133a low expression group. The relationship between the expression levels of TPD52 and miR-133a and the clinicopathological features of patients with pancreatic cancer was analyzed. The COX regression model was used to analyze the risk factors affecting the prognosis of patients with pancreatic cancer. Results: The high expression rate of TPD52 and the low expression rate of miR-133a in pancreatic cancer tissues were higher than those in normal paracancerous tissues(P<0.05). Based on the comparison of prognosis and survival, the median survival time of patients with high expression of TPD52 and low expression of miR-133a was lower than that of patients with low expression of TPD52 and high expression of miR-133a, with a statistically significant difference(P<0.05). Moreover, multivariate Cox regression analysis showed that low differentiation of pancreatic cancer, III-IV stage of TNM, high expression of TPD52, as well as low expression of miR-133a were independent risk factors for postoperative survival of patients with pancreatic cancer(P<0.05). Conclusion: TPD52 is expressed at a high level whereas miR-133a at a low level in pancreatic cancer tissues, both of which together with low differentiation of pancreatic cancer and III-IV stage of TNM constitute independent risk factors affecting the surgical prognosis of patients with pancreatic cancer.

Evaluating the efficacy of balloon pulmonary angioplasty using quantitative analysis of SPECT pulmonary ventilation/perfusion scintigraphy in patients with chronic thromboembolic pulmonary hypertension.

Background: Single-photon emission computed tomography (SPECT) ventilation perfusion imaging is the main imaging method for the diagnosis of pulmonary embolism, and its application in the diagnosis and efficacy evaluation of chronic thromboembolic pulmonary hypertension (CTEPH) has been paid more and more attention. In recent years, with the development of computer software technology, ventilation/perfusion (V/Q) imaging quantitative analysis technology has become more and more mature. The objective of this study was to investigate the utility of quantitative analysis of pulmonary V/Q scintigraphy in evaluating the efficacy of balloon pulmonary angioplasty (BPA) in patients with CTEPH. Methods: In this retrospective analysis, we collected data of patients diagnosed with CTEPH who underwent BPA at the China-Japan Friendship Hospital from April 2018 to September 2020. The sample consisted of 23 males and 28 females, with an average age of 55.1±12.7 years. All patients underwent V/Q scintigraphy within one week before surgery, and we reviewed the pulmonary angiography within 1-3 months following the last BPA procedure. We repeated V/Q scintigraphy within 1 week before or after the pulmonary angiography, at the time of collecting clinical and hemodynamic parameters of these patients. We divided the patients into two groups based on the presence of residual pulmonary hypertension post-surgery and compared the pre- and post-operative quantitative pulmonary perfusion defect percentage scores (PPDs%) using the t-test. Results: In all, 102 V/Q scintigraphy scans were performed in 51 patients. The quantitative PPDs% were positively correlated with the hemodynamic indexes mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and mean right ventricular pressure (RVP) (r=0.605, 0.391, and 0.464, respectively, all P<0.001) and negatively correlated with the 6-minute walking distance (6MWD) (r=-0.254, P=0.010). The average preoperative quantitative PPDs% were (49.0±15.6)% which significantly decreased to (33.5±13.9)% after surgery (t=11.249, P<0.001). The preoperative quantitative PPDs% were (54.7±15.7)% and (44.0±13.8)% in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=2.599, P=0.012). The postoperative quantitative PPDs% were (41.5±12.5)% and (26.3±11.0)%, in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=4.647, P<0.001). Conclusions: In this study, we found that quantitative analysis of SPECT pulmonary V/Q scintigraphy adequately reflected the pulmonary artery pressure and clinical status in patients with CTEPH. Our results demonstrate its definite utility in predicting residual pulmonary hypertension and in evaluating the postoperative efficacy of BPA in patients with CTEPH.

The dimeric deubiquitinase USP28 integrates 53BP1 and MYC functions to limit DNA damage.

DNA replication is a major source of endogenous DNA damage in tumor cells and a key target of cellular response to genotoxic stress. DNA replication can be deregulated by oncoproteins, such as transcription factor MYC, aberrantly activated in many human cancers. MYC is stringently regulated by the ubiquitin system - for example, ubiquitination controls recruitment of the elongation factor PAF1c, instrumental in MYC activity. Curiously, a key MYC-targeting deubiquitinase USP28 also controls cellular response to DNA damage via the mediator protein 53BP1. USP28 forms stable dimers, but the biological role of USP28 dimerization is unknown. We show here that dimerization limits USP28 activity and restricts recruitment of PAF1c by MYC. Expression of monomeric USP28 stabilizes MYC and promotes PAF1c recruitment, leading to ectopic DNA synthesis and replication-associated DNA damage. USP28 dimerization is stimulated by 53BP1, which selectively binds USP28 dimers. Genotoxic stress diminishes 53BP1-USP28 interaction, promotes disassembly of USP28 dimers and stimulates PAF1c recruitment by MYC. This triggers firing of DNA replication origins during early response to genotoxins and exacerbates DNA damage. We propose that dimerization of USP28 prevents ectopic DNA replication at transcriptionally active chromatin to maintain genome stability.

Clinical outcomes and risk factors of non-curative endoscopic submucosal dissection for early gastric cancer: a retrospective multicenter study in Zhejiang, China.

Background: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) does not always lead to curative resection. Risk factors of lymph node metastasis (LNM)/local cancer residue after non-curative ESD for EGC have not been fully elucidated. We therefore aimed to clarify them and evaluate whether the "eCura system" is reliable for the risk stratification of LNM after non-curative ESD. Methods: We conducted a multicenter retrospective study at seven institutions in Zhejiang, China, on 128 patients who underwent non-curative ESD for EGC. We divided the patients into two groups according to their therapeutic regimen after non-curative ESD. We analyzed the risk factors for LNM, local cancer residue, cancer recurrence, and cancer-specific mortality. Furthermore, we compared the outcomes in each risk category after applying the "eCura system". Results: Among 68 patients undergoing additional surgery, LNM was found in three (4.41%) patients, while local cancer residue was found in eight (11.76%) patients. Multivariate analysis showed that upper third location and deep submucosal invasion were independent risk factors of LNM and local cancer residue. Among 60 patients who underwent simple follow-up, local cancer recurrence was found in four (6.67%) patients and cancer-specific mortality was found in one (1.67%) patient. There were no independent risk factors of cancer recurrence and cancer-specific mortality in our study. During the follow-up period, 5-year overall survival (OS) and disease-free survival (DFS) were 93.8% and 88.9%, respectively. Additionally, LNM and cancer recurrence were significantly associated with the eCura scoring system (p = 0.044 and p = 0.017, respectively), while local cancer residue and cancer-specific mortality were not (p = 0.478 and p = 0.131, respectively). Conclusion: Clinicians should be aware of the risk factors for the prognosis of patients with non-curative ESD to determine subsequent treatment. Through the application of the "eCura system", additional surgery should be performed in patients with intermediate/high risk of LNM.

Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer.

Metastasis is a fatal status for liver cancer, and the identification of an effective prediction model and promising therapeutic target is essential. Given the known relationship between fatty acid (FA) metabolism and the liver, the present study aimed to investigate dysregulation of genes associated with FA metabolism in liver cancer. Bioinformatics analyses were performed on data from patients with hepatocellular carcinoma (HCC) obtained from The Cancer Genome Atlas database using R software packages. Online public tools such as the Human Protein Atlas, Tumor Immune Single-Cell Hub and the University of Alabama at Birmingham Cancer Data Analysis portal were also utilized. Some essential results were further verified using in vitro experiments using HepG2 liver cancer cells. A signature consisting of three genes associated with the progression and prognosis of HCC and FA metabolism was identified. When samples were scored based on the expression of these genes and divided according to the median value, the higher score group showed a worse outcome and repressive immune microenvironment than the lower score group. Downstream pathways such as hypoxia, IL6/JAK/STAT3 and epithelial-mesenchymal transition were found to be significantly activated in the higher score group. As the core factor in the signature, mitochondrial ribosomal protein L35 (MRPL35) was found to be upregulated in HCC and to have certain impacts on the dysregulation of effective immunity. Further investigations and in vitro experiments indicated that MRPL35 facilitates the migration and invasion abilities of liver cancer, and the resistance of HCC to treatment. These findings have important implications regarding the characteristics and mechanisms of metastasis in liver cancer, and provide a promising signature based on FA metabolism-related genes that may be used to predict outcomes and explored as a novel therapeutic target in liver cancer.

Value of Echocardiography and Cardiac Magnetic resonance in assessing left ventricular function in breast and gastric cancer patients after Anthracycline Chemotherapy.

BACKGROUND: Echocardiography (ECHO) and cardiac magnetic resonance imaging (MRI) are used to observe changes in the left ventricular structure in patients with breast and gastric cancer after 6 cycles of chemotherapy. Based on the observed values, we aimed to evaluate the cardiotoxicity of anthracyclines in cancer patients and to analyze the consistency of the two examination methods in assessing left ventricular function after chemotherapy. METHODS: From January 2020 to January 2022, the data of 80 patients with malignant tumors who received anthracycline chemotherapy (breast cancer, n = 40; gastric cancer, n = 40) and 40 healthy volunteers (Control group) were retrospectively collected. Serum high-sensitivity cardiac troponin T (hs-cTnT) levels were detected by an automatic immunoassay analyzer. Left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were measured by cardiac MRI and 2-dimensional ECHO using the biplane Simpson's method. RESULTS: Compared with baseline values, serum high-sensitivity cardiac troponin T (hs-cTnT) levels were significantly increased in patients with breast cancer and gastric cancer after 6 cycles of chemotherapy (P < 0.05). In addition, LVEDV, LVESV and LVEF measured with MRI were higher than those detected by ECHO in cancer patients after 6 cycles of chemotherapy (P < 0.05). And the Bland-Altman plot analysis showed that LVEDV, LVESV and LVEF measured by the two examination methods were in good agreement. CONCLUSION: Breast and gastric cancer patients exhibited elevated levels of hs-cTnT after 6 cycles of chemotherapy, indicating potential cardiotoxicity. Additionally, cardiac MRI and 2-dimensional ECHO showed good agreement in assessing left ventricular function, with ECHO tending to underestimate volume measurements compared to MRI.

Trim33 masks a non-transcriptional function of E2f4 in replication fork progression.

Replicative stress promotes genomic instability and tumorigenesis but also presents an effective therapeutic endpoint, rationalizing detailed analysis of pathways that control DNA replication. We show here that the transcription factor E2f4 recruits the DNA helicase Recql to facilitate progression of DNA replication forks upon drug- or oncogene-induced replicative stress. In unperturbed cells, the Trim33 ubiquitin ligase targets E2f4 for degradation, limiting its genomic binding and interactions with Recql. Replicative stress blunts Trim33-dependent ubiquitination of E2f4, which stimulates transient Recql recruitment to chromatin and facilitates recovery of DNA synthesis. In contrast, deletion of Trim33 induces chronic genome-wide recruitment of Recql and strongly accelerates DNA replication under stress, compromising checkpoint signaling and DNA repair. Depletion of Trim33 in Myc-overexpressing cells leads to accumulation of replication-associated DNA damage and delays Myc-driven tumorigenesis. We propose that the Trim33-E2f4-Recql axis controls progression of DNA replication forks along transcriptionally active chromatin to maintain genome integrity.

RNAPII-dependent ATM signaling at collisions with replication forks.

Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and are thought to underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII nucleates activation of the ATM kinase at TRCs to stimulate DNA repair. We show the ATPase WRNIP1 associates with RNAPII and limits ATM activation during unperturbed cell cycle. WRNIP1 binding to elongating RNAPII requires catalytic activity of the ubiquitin ligase HUWE1. Mutation of HUWE1 induces TRCs, promotes WRNIP1 dissociation from RNAPII and binding to the replisome, stimulating ATM recruitment and activation at RNAPII. TRCs and translocation of WRNIP1 are rapidly induced in response to hydroxyurea treatment to activate ATM and facilitate subsequent DNA repair. We propose that TRCs can provide a controlled mechanism for stalling of replication forks and ATM activation, instrumental in cellular response to replicative stress.

Facile production of cellulose nanofibers from raw elephant grass by an aluminum chloride-enhanced acidic deep eutectic solvent.

To develop a greener and more efficient method for producing cellulose nanofibers (CNFs) from raw plants, an AlCl3-enhanced ternary deep eutectic solvent, DES2 (consisting of choline chloride, citric acid, and AlCl3·6H2O in a molar ratio of 1:0.4:0.08), was synthesized. Raw elephant grass (EG) was pretreated with DES2, followed by sodium chlorite (NaClO2) bleaching and ultrasonic disruption to extract high-performance CNFs. The DES2 and NaClO2 treatments effectively removed hemicellulose and lignin, achieving removal rates of 99.23 % and 99.62 %, respectively, while maintaining a cellulose content of 78.3 %. DES2 demonstrated easy recyclability and maintained excellent biomass pretreatment performance even after multiple cycles. Following a brief 30-min intermittent ultrasound treatment, the resulting CNFs demonstrated superior crystallinity, increased carboxyl content, and a narrower width distribution compared to CNFs obtained from AlCl3-free DES1. Optimized conditions at 110 °C yielded CNFs with 85.3 % crystallinity, 0.64 mmol/g carboxyl content, 5.15 nm width distribution, and excellent dispersion in water for at least six months. Additionally, CNFs enhanced the tensile strength of chia seed mucilage (CM) composite films, showing a significant improvement to 26.6 MPa, representing a 231.3 % increase over the control film. This study offers a promising approach for efficiently producing CNFs from raw plants.

New Insights into the Role of Natural Organic Matter in Fe-Cr Coprecipitation: Importance of Molecular Selectivity.

Coprecipitation of Fe/Cr hydroxides with natural organic matter (NOM) is an important pathway for Cr immobilization. However, the role of NOM in coprecipitation is still controversial due to its molecular heterogeneity and diversity. This study focused on the molecular selectivity of NOM toward Fe/Cr coprecipitates to uncover the fate of Cr via Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS). The results showed that the significant effects of Suwannee River NOM (SRNOM) on Cr immobilization and stability of the Fe/Cr coprecipitates did not merely depend on the adsorption of SRNOM on Fe/Cr hydroxides. FT-ICR-MS spectra suggested that two pathways of molecular selectivity of SRNOM in the coprecipitation affected Cr immobilization. Polycyclic aromatics and polyphenolic compounds in SRNOM preferentially adsorbed on the Fe/Cr hydroxide nanoparticles, which provided extra binding sites and promoted the aggregation. Notably, some specific compounds (i.e., polyphenolic compounds and highly unsaturated phenolic compounds), less unsaturated and more oxygenated than those adsorbed on Fe/Cr hydroxide nanoparticles, were preferentially incorporated into the insoluble Cr-organic complexes in the coprecipitates. Kendrick mass defect analysis revealed that the insoluble Cr-organic complexes contained fewer carbonylated homologous compounds. More importantly, the spatial distribution of insoluble Cr-organic complexes was strongly related to Cr immobilization and stability of the Fe/Cr-NOM coprecipitates. The molecular information of the Fe/Cr-NOM coprecipitates would be beneficial for a better understanding of the transport and fate of Cr and exploration of the related remediation strategy.

Dietary Protein Regulates Female Estrous Cyclicity Partially via Fibroblast Growth Factor 21.

Fibroblast growth factor 21 (FGF21), a hormone predominantly released in the liver, has emerged as a critical endocrine signal of dietary protein intake, but its role in the control of estrous cyclicity by dietary protein remains uncertain. To investigated the role of FGF21 and hypothalamic changes in the regulation of estrous cyclicity by dietary protein intake, female adult Sprague-Dawley rats with normal estrous cycles were fed diets with protein contents of 4% (P4), 8% (P8), 13% (P13), 18% (P18), and 23% (P23). FGF21 liver-specific knockout or wild-type mice were fed P18 or P4 diets to examine the role of liver FGF21 in the control of estrous cyclicity. Dietary protein restriction resulted in no negative effects on estrous cyclicity or ovarian follicular development when the protein content was greater than 8%. Protein restriction at 4% resulted in decreased bodyweight, compromised Kiss-1 expression in the hypothalamus, disturbed estrous cyclicity, and inhibited uterine and ovarian follicular development. The disturbed estrous cyclicity in rats that received the P4 diet was reversed after feeding with the P18 diet. Liver Fgf21 mRNA expressions and serum FGF21 levels were significantly increased as dietary protein content decreased, and loss of hepatic FGF21 delayed the onset of cyclicity disruption in rats fed with the P4 diet, possibly due to the regulation of insulin-like growth factor-1. Collectively, severe dietary protein restriction results in the cessation of estrous cyclicity and ovarian follicle development, and hepatic FGF21 and hypothalamic Kiss-1 were partially required for this process.

Hourglass-like constriction of the anterior interosseous nerve in the left forearm: A case report.

BACKGROUND: Hourglass-like constriction neuropathy is a rare neurological disorder. The main clinical manifestation is peripheral nerve injury with no apparent cause, and the pathomorphological change is an unexplained narrowing of the diseased nerve. The diagnosis and treatment of the disease are challenging and there is no accepted diagnostic or therapeutic approach. CASE SUMMARY: This report describes a rare hourglass constriction of the anterior interosseous nerve in the left forearm in a 47-year-old healthy male who was treated surgically and gradually recovered function over a 6-mo follow-up period. CONCLUSION: Hourglass-like constriction neuropathy is a rare disorder. With the development of medical technology, more examinations are now available for diagnosis. This case aims to highlight the rare manifestations of Hourglass-like constriction neuropathy and provides a reference for enriching the clinical diagnosis and treatment experience.

Effect of iron-loaded sludge biochar amendments on phytoremediation potential of Cr-contaminated soils by Leersia hexandra swartz.

In this study, the effect of iron-loaded sludge biochar (ISBC) with different amendment dosages (mass ratio of biochar to soil equal to 0, 0.01, 0.025 and 0.05) on the phytoremediation potential of Leersia hexandra swartz (L. hexandra) to Cr-contaminated soil was investigated. With increasing ISBC dosage from 0 to 0.05, plant height, aerial tissue biomass and root biomass increased from 15.70 cm, 0.152 g pot-1 and 0.058 g pot-1 to 24.33 cm, 0.304 g pot-1 and 0.125 g pot-1, respectively. Simultaneously, the Cr contents in aerial tissues and roots increased from 1039.68 mg kg-1 to 2427.87 mg kg-1 to 1526.57 mg kg-1 and 3242.62 mg kg-1, respectively. Thus, the corresponding bioenrichment factor (BCF), bioaccumulation factor (BAF), total phytoextraction (TPE) and translocation factor (TF) values were also increased from 10.52, 6.20, 0.158 mg pot-1 (aerial tissue)/0.140 mg pot-1 (roots) and 0.428 to 15.15, 9.42, 0.464 mg pot-1 (aerial tissue)/0.405 mg pot-1 (roots) and 0.471, respectively. The significant positive effect of ISBC amendment was primarily attributed to the following three aspects: 1) the root resistance index (RRI), tolerance index (TI) and growth toxicity index (GTI) of L. hexandra to Cr were increased from 100%, 100% and 0%-216.88%, 155.02% and 42.18%, respectively; 2) the bio-available Cr content in the soil was decreased from 1.89 mg L-1 to 1.48 mg L-1, while the corresponding TU (toxicity units) value was declined from 0.303 to 0.217; 3) the activities of urease, sucrase and alkaline phosphatase in soil were increased from 0.186 mg g-1, 1.40 mg g-1 and 0.156 mg g-1 to 0.242 mg g-1, 1.86 mg g-1 and 0.287 mg g-1, respectively. In summary, ISBC amendment was able to significantly improve the phytoremediation of Cr-contaminated soils by L. hexandra.

Assessment of Helicobacter pylori infection by deep learning based on endoscopic videos in real time.

BACKGROUND AND AIMS: Endoscopic assessment of Helicobacter pylori infection is a simple and effective method. Here, we aimed to develop a deep learning-based system named Intelligent Detection Endoscopic Assistant-Helicobacter pylori (IDEA-HP) to assess H. pylori infection by using endoscopic videos in real time. METHODS: Endoscopic data were retrospectively obtained from Zhejiang Cancer Hospital (ZJCH) for the development, validation, and testing of the system. Stored videos from ZJCH were used for assessing and comparing the performance of IDEA-HP with that of endoscopists. Prospective consecutive patients undergoing esophagogastroduodenoscopy were enrolled to assess the applicability of clinical practice. The urea breath test was used as the gold standard for diagnosing H. pylori infection. RESULTS: In 100 videos, IDEA-HP achieved a similar overall accuracy of assessing H. pylori infection to that of experts (84.0% vs. 83.6% [P = 0.729]). Nevertheless, the diagnostic accuracy (84.0% vs. 74.0% [P<0.001]) and sensitivity (82.0% vs. 67.2% [P<0.001]) of IDEA-HP were significantly higher than those of the beginners. In 191 prospective consecutive patients, IDEA-HP achieved accuracy, sensitivity, and specificity of 85.3% (95% CI: 79.0%-89.3%), 83.3% (95% CI: 72.8%-90.5%), and 85.8% (95% CI: 77.7%-91.4%), respectively. CONCLUSIONS: Our results show that IDEA-HP has great potential for assisting endoscopists in assessing H. pylori infection status during actual clinical work.

An electrochemical sensor for direct and sensitive detection of ketamine.

Ketamine is an organic drug with weak electrochemical activity, which makes it difficult to directly detect by electrochemical methods. Herein, an electrochemical sensor, with excellent detection sensitivity, is proposed for direct detection of ketamine based on a weakly conductive poly-L-cysteine molecularly imprinted membrane. Poly-L-cysteine molecularly imprinted membrane sensor (poly-L-Cys-KT-MIM/GCE) is obtained using L-cysteine as a functional monomer and ketamine as a template molecule based on electropolymerization. The green and highly active cysteine is selected as a functional monomer during electropolymerization, which cannot only achieve specific recognition but also improve detection sensitivity. Furthermore, the oxidation mechanism and fingerprint of ketamine on the electrode surface are established by analyzing the corresponding oxidation products using high/resolution mass spectrometry, which will help to promote the application of electrochemistry in the rapid detection of drugs. Under optimal conditions, the as-designed sensor demonstrated a linear response to ketamine within the range of 5.0 × 10-7 to 2.0 × 10-5 mol L-1 and a detection limit of 1.6 × 10-7 mol L-1. The proposed method exhibited excellent performance from the viewpoints of selectivity, sensitivity and stability. Notably, the sensor rendered excellent reliability and could be used for the detection of target analytes in hair and urine samples with high recovery rates.

An MRI-based Radiomics Approach to Improve Breast Cancer Histological Grading.

RATIONALE AND OBJECTIVES: Nottingham histological grade (NHG) 2 breast cancer has an intermediate risk of recurrence, which is not informative for therapeutic decision-making. We sought to develop and independently validate an MRI-based radiomics signature (Rad-Grade) to improve prognostic re-stratification of NHG 2 tumors. MATERIALS AND METHODS: Nine hundred-eight subjects with invasive breast cancer and preoperative MRI scans were retrospectively obtained. The NHG 1 and 3 tumors were randomly split into training and independent test cohort, with the NHG 2 as the prognostic validation set. From MRI image features, a radiomics-based signature predictive of the histological grade was built by use of the LASSO logistic regression algorithm. The model was developed for identifying NHG 1 and 3 radiological patterns, followed with re-stratification of NHG 2 tumors into Rad-Grade (RG)2-low (NHG 1-like) and RG2-high (NHG 3-like) subtypes using the learned patterns, and the prognostic value was assessed in terms of recurrence-free survival (RFS). RESULTS: The Rad-Grade showed independent prognostic value for re-stratification of NHG 2 tumors, where RG2-high had an increased risk for recurrence (HR 2.20, 1.10-4.40, p = 0.026) compared with RG2-low after adjusting for established risk factors. RG2-low shared similar phenotypic characteristics and RFS outcomes with NHG 1, and RG2-high with NHG 3, revealing that the model captures radiomic features in NHG 2 that are associated with different aggressiveness. The prognostic value of Rad-Grade was further validated in the NHG2 ER+ (HR 2.53, 1.13-5.56, p = 0.023) and NHG 2 ER+LN- (HR 5.72, 1.24-26.44, p = 0.025) subgroups, and in specific treatment contexts. CONCLUSION: The radiomics-based re-stratification of NHG 2 tumors offers a cost-effective promising alternative to gene expression profiling for tumor grading and thus may improve clinical decisions.

Esketamine-based opioid-free anaesthesia alleviates postoperative nausea and vomiting in patients who underwent laparoscopic surgery: study protocol for a randomized, double-blinded, multicentre trial.

BACKGROUND: Although opioids are commonly prescribed in clinical anaesthesia, the significant side effects attributed to their overuse are raising increasing concerns. One way to reduce perioperative opioid consumption is to apply opioid-reduced anaesthesia (ORA) and even opioid-free anaesthesia (OFA), which involves regional techniques, neuraxial anaesthesia, nonopioid analgesics or combined use. The aim of this study was to investigate whether the application of OFA by using esketamine in intraoperative analgesia could minimize the side effects of postoperative nausea and vomiting (PONV), as well as other short-term side effects related to anaesthesia. METHODS/DESIGN: The study was designed as a prospective, randomized, controlled, multicentre trial. A total of 278 patients were enrolled; participants were nonsmoking female patients aged 18-50 years and scheduled for laparoscopic appendectomy or cholecystectomy, ASA at I-III, with no serious physical or mental diseases. Both groups received usual perioperative care except for the analgesic medication of either esketamine or sufentanil. The primary outcome was the incidence of PONV 3 days after surgery. Secondary outcomes included recovery status, pain, sedation level and overall recovery, delirium and cognition, anxiety and depression and total consumption of analgesic agents. DISCUSSION: This trial may show that the synergy of esketamine and propofol anaesthesia reduces PONV as well as other short-term adverse events, thereby providing a better safety and satisfaction profile of ERAS for laparoscopic appendectomy and cholecystectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100047169. Registered on June 9, 2021.

Effect of different doses of dexmedetomidine on the median effective concentration of propofol during gastrointestinal endoscopy: a randomized controlled trial.

AIMS: Dexmedetomidine could be an ideal adjuvant to propofol during gastrointestinal endoscopy because it provides both analgesia and sedation without respiratory depression. This study investigates the effect of different doses of dexmedetomidine on the median effective concentration of propofol during gastrointestinal endoscopy. METHODS: Ninety adult patients were randomly assigned to Group Control, Group DEX0.5 (0.5 µg/kg dexmedetomidine) or Group DEX1.0 (1.0 µg/kg dexmedetomidine). Anaesthesia during endoscopy was implemented by plasma target-controlled infusion (TCI) of propofol with different doses of dexmedetomidine. TCI concentration of the first patient for each group was 2.5 µg/mL and the consecutive adjacent concentration gradient was 0.5 µg/mL. Median effective concentration (EC50 ) of propofol by TCI for gastrointestinal endoscopy was determined by using the modified Dixon's up-and-down method. Cardiovascular variables were also measured. RESULTS: EC50 of propofol by TCI and 95% confidence interval (CI) for gastrointestinal endoscopy were 3.77 (3.48-4.09), 2.51 (2.27-2.78) and 2.10 (1.90-2.33) µg/mL in Group Control, Group DEX0.5 and Group DEX1.0, respectively. The average percent change from heart rate (HR) baseline was 2.8 (8.9), -7.4 (7.7) and -10.5 (8.8) (P < .001), and the average percent change from mean arterial pressure (MAP) baseline was -10.6 [-24.7; 3.5], -9.5 [-29.2; 11.4] and -4.0 [-27.3; 15.5] (P = .034) in Group Control, Group DEX0.5 and Group DEX1.0, respectively. CONCLUSIONS: Dexmedetomidine reduced the EC50 of propofol by TCI. A 0.5-1 µg/kg dose of dexmedetomidine caused a decrease in HR without bradycardia. The decrease in dosage of propofol with increasing doses of dexmedetomidine caused more stable MAP. Dexmedetomidine is an ideal adjuvant drug to propofol during gastrointestinal endoscopy.

Myeloid sarcoma with ulnar nerve entrapment: A case report.

BACKGROUND: Myeloid sarcoma (MS) is relatively rare, occurring mainly in the skin and lymph nodes, and MS invasion of the ulnar nerve is particularly unusual. The main aim of this article is to present a case of MS invading the brachial plexus, causing ulnar nerve entrapment syndrome, and to further clinical understanding of the possibility of MS invasion of peripheral nerves. CASE SUMMARY: We present the case of a 46-year-old man with a 13-year history of well-treated acute nonlymphocytic leukaemia who was admitted to the hospital after presenting with numbness and pain in his left little finger. The initial diagnosis was considered a simple case of nerve entrapment disease, with magnetic resonance imaging showing slightly abnormal left brachial plexus nerve alignment with local thickening, entrapment, and high signal on compression lipid images. Due to the severity of the ulnar nerve compression, we surgically investigated and cleared the entrapment and nerve tissue hyperplasia; however, subsequent pathological biopsy results revealed evidence of MS. The patient had significant relief from his neurological symptoms, with no postoperative complications, and was referred to the haemato-oncology department for further consultation about the primary disease. This is the first report of safe treatment of ulnar nerve entrapment from MS. It is intended to inform hand surgeons that nerve entrapment may be associated with extramedullary MS, as a rare presenting feature of the disease. CONCLUSION: MS invasion of the brachial plexus and surrounding tissues of the upper arm, resulting in ulnar nerve entrapment and degeneration with significant neurological pain and numbness in the little finger, is uncommon. Surgical treatment significantly relieved the patient's nerve entrapment symptoms and prevented further neurological impairment. This case is reported to highlight the rare presenting features of MS.