Tetrodotoxin and the state-of-the-art progress of its associated analytical methods.

Tetrodotoxin (TTX), which is found in various marine organisms, including pufferfish, shellfish, shrimp, crab, marine gastropods, and gobies, is an effective marine toxin and the cause of many seafood poisoning incidents. Owing to its toxicity and threat to public health, the development of simple, rapid, and efficient analytical methods to detect TTX in various food matrices has garnered increasing interest worldwide. Herein, we reviewed the structure and properties, origin and sources, toxicity and poisoning, and relevant legislative measures of TTX. Additionally, we have mainly reviewed the state-of-the-art progress of analytical methods for TTX detection in the past five years, such as bioassays, immunoassays, instrumental analysis, and biosensors, and summarized their advantages and limitations. Furthermore, this review provides an in-depth discussion of the most advanced biosensors, including cell-based biosensors, immunosensors, and aptasensors. Overall, this study provides useful insights into the future development and wide application of biosensors for TTX detection.

Generating Synthesized Fluorescein Angiography Images From Color Fundus Images by Generative Adversarial Networks for Macular Edema Assessment.

Purpose: To assess the feasibility of generating synthetic fluorescein angiography (FA) images from color fundus (CF) images using pixel-to-pixel generative adversarial network (pix2pixGANs) for clinical applications. Research questions addressed image realism to retinal specialists and utility for assessing macular edema (ME) in Retinal Vein Occlusion (RVO) eyes. Methods: We used a registration-guided pix2pixGANs method trained on the CF-FA dataset from Kham Eye Centre, Kandze Prefecture People's Hospital. A visual Turing test confirmed the realism of synthetic images without novel artifacts. We then assessed the synthetic FA images for assessing ME. Finally, we quantitatively evaluated the synthetic images using Fréchet Inception distance (FID) and structural similarity measures (SSIM). Results: The raw development dataset had 881 image pairs from 349 subjects. Our approach is capable of generating realistic FA images because small vessels are clearly visible and sharp within one optic disc diameter around the macula. Two retinal specialists agreed that more than 85% of synthetic FA images have good or excellent image quality. For ME detection, accuracy was similar for real and synthetic images. FID demonstrated a 38.9% improvement over the previous state-of-the-art (SOTA), and SSIM reached 0.78 compared to the previous SOTA's 0.67. Conclusions: We developed a pix2pixGANs model translating FA images from label-free CF images, yielding reliable synthetic FA images. This suggests potential for noninvasive evaluation of ME in RVO eyes using pix2pix GANs techniques. Translational Relevance: Pix2pixGANs techniques have the potential to assist in the noninvasive clinical assessment of ME in RVO eyes.

Proprotein convertase subtilisin/kexin type 9 inhibitors protect against contrast-associated acute kidney injury in patients with atherosclerotic cardiovascular disease.

Background and aims: Contrast-associated acute kidney injury (CA-AKI) may occur in patients undergoing medical procedures involving x-rays and radiocontrast media, potentially resulting in prolonged renal impairment. However, no effective treatments are available. Therefore, this study aimed to investigate the efficacy of evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in reducing CA-AKI incidence among patients with atherosclerotic cardiovascular disease (ASCVD) undergoing percutaneous coronary intervention. Methods: This retrospective cohort study included patients who underwent percutaneous coronary intervention between January 2020 and December 2021 at Tianjin Chest Hospital. The study endpoint was CA-AKI incidence, and the impact of selection bias and other potential confounding factors was mitigated using bias matching. Overall, 1,642 patients were included in this study: 821 patients received evolocumab treatment before contrast agent application, and 821 did not receive such treatment. Results: CA-AKI incidence was 6.21% and 8.04% in the evolocumab and control groups, respectively. After propensity-score matching, the incidence rate was 5.09% and 14.16% in the evolocumab and control groups, respectively. Evolocumab treatment significantly reduced CA-AKI incidence (p < 0.001). Consistent findings were obtained in the subgroups of individuals with type II diabetes mellitus, chronic heart failure, and hypertension. Evolocumab exhibited a significantly greater protective effect in the high- and extremely high-risk populations than in the low- and middle-risk populations (p < 0.001). Conclusions: Evolocumab administration significantly reduced CA-AKI incidence among patients with ASCVD. Notably, this effect was more prominent within the subset of high- and extremely high-risk individuals who were already experiencing CA-AKI.

Purple sweet potato anthocyanins normalize the blood glucose concentration and restore the gut microbiota in mice with type 2 diabetes mellitus.

Background: This study investigated the effects of purple sweet potato anthocyanins (PSPA) in a type 2 diabetes mellitus (T2DM) mouse model. Methods: Sixty-five male mice were randomly divided into one control group and four experimental groups, which were fed with a high-fat diet and intraperitoneally injected with streptozotocin (STZ) to induce T2DM. The model mice were treated with 0 (M), 227.5 (LP), 455 (MP), or 910 (HP) mg/kg PSPA for ten days. ELISA, 16S rRNA sequencing, and hematoxylin and eosin staining were used to assess blood biochemical parameters, gut microbial composition, and liver tissue structure, respectively. Results: The FBG concentration was significantly decreased in the LP (6.32 ± 1.05 mmol/L), MP (6.32 ± 1.05 mmol/L), and HP (5.65 ± 0.83 mmol/L) groups; the glycosylated hemoglobin levels were significantly decreased in the HP group (14.43 ± 7.12 pg/mL) compared with that in the M group (8.08 ± 1.04 mmol/L; 27.20 ± 7.72 pg/mL; P < 0.05). The PSPA treated groups also increased blood glutathione levels compared with M. PSPA significantly affected gut microbial diversity. The Firmicutes/Bacteroidetes ratio decreased by 38.9 %, 49.2 %, and 15.9 % in the LP, MP, and HP groups compared with that in the M group (0.62). The PSPAs treated groups showed an increased relative abundance of Lachnospiraceae_Clostridium, Butyricimonas, and Akkermansia and decreased abundance of nine bacterial genera, including Staphylococcus. Conclusion: PSPA reduced blood glucose levels, increased serum antioxidant enzymes, and optimized the diversity and structure of the gut microbiota in mice with T2DM.

A smartphone-based fluorescent biosensor with metal-organic framework biocomposites and cotton swabs for the rapid determination of tetrodotoxin in seafood.

BACKGROUND: Tetrodotoxin (TTX) is a potent neurovirulent marine biotoxin that is present in puffer fish and certain marine animals. It is capable of causing severe neurotoxic symptoms and even death when consumed through contaminated seafood. Due to its high toxicity, developing an effective assay for TTX determination in seafood has significant benefits for food safety and human health. Currently, it remains challenging to achieve on-site determination of TTX in seafood. To facilitate mass on-site assays, more affordable technologies utilizing accessible equipment that require no skilled personnel are needed. RESULTS: A smartphone-based portable fluorescent biosensor is proposed for TTX determination by using metal-organic framework (MOF) biocomposites and cotton swabs. Oriented antibody (Ab)-decorated and fluorescent quantum dot (QD)-loaded MOF biocomposites (QD@MOF*Ab) are rapidly synthesized for binding targets and fluorescent responses by utilizing the tunability of zinc-based MOF. Moreover, facile Ab-immobilized household cotton swabs are utilized as TTX capture tools. TTX forms sandwich immune complexes with QD@MOF*Ab probes, achieving signal amplification. These probes are excited by a portable device to generate bright fluorescent signals, which can be detected by the naked eye, and TTX quantitative results are obtained using a smartphone. When observed with the naked eye, the limit of detection (LOD) is 0.4 ng/mL, while intelligent quantitation presents an LOD of 0.13 ng/mL at logarithmic concentrations of 0.2-400 ng/mL. SIGNIFICANCE: This biosensor is convenient to use, and an easy-to-operate analysis is completed within 15 min, thus demonstrating excellent performance in terms of detection speed and portability. Furthermore, it successfully determines TTX contents in puffer fish and clam samples, demonstrating its potential for monitoring seafood. Herein, this work provides a favorable rapid sensing platform that is easily portable.

Metabolism, Disposition, Excretion, and Potential Transporter Inhibition of 7-16, an Improving 5-HT2A Receptor Antagonist and Inverse Agonist for Parkinson's Disease.

Compound 7-16 was designed and synthesized in our previous study and was identified as a more potential selective 5-HT2A receptor antagonist and inverse agonist for treating Parkinson's disease psychosis (PDP). Then, the metabolism, disposition, and excretion properties of 7-16 and its potential inhibition on transporters were investigated in this study to highlight advancements in the understanding of its therapeutic mechanisms. The results indicate that a total of 10 metabolites of 7-16/[14C]7-16 were identified and determined in five species of liver microsomes and in rats using UPLC-Q Exactive high-resolution mass spectrometry combined with radioanalysis. Metabolites formed in human liver microsomes could be covered by animal species. 7-16 is mainly metabolized through mono-oxidation (M470-2) and N-demethylation (M440), and the CYP3A4 isozyme was responsible for both metabolic reactions. Based on the excretion data in bile and urine, the absorption rate of 7-16 was at least 74.7%. 7-16 had weak inhibition on P-glycoprotein and no effect on the transport activity of OATP1B1, OATP1B3, OAT1, OAT3, and OCT2 transporters. The comprehensive pharmacokinetic properties indicate that 7-16 deserves further development as a new treatment drug for PDP.

Development and validation of a nomogram to predict postoperative delirium in older patients after major abdominal surgery: a retrospective case-control study.

BACKGROUND: Postoperative delirium is a common complication in older patients, with poor long-term outcomes. This study aimed to investigate risk factors and develop a predictive model for postoperative delirium in older patients after major abdominal surgery. METHODS: This study retrospectively recruited 7577 patients aged ≥ 65 years who underwent major abdominal surgery between January 2014 and December 2018 in a single hospital in Beijing, China. Patients were divided into a training cohort (n = 5303) and a validation cohort (n = 2224) for univariate and multivariate logistic regression analyses and to build a nomogram. Data were collected for 43 perioperative variables, including demographics, medical history, preoperative laboratory results, imaging, and anesthesia information. RESULTS: Age, chronic obstructive pulmonary disease, white blood cell count, glucose, total protein, creatinine, emergency surgery, and anesthesia time were associated with postoperative delirium in multivariate analysis. We developed a nomogram based on the above 8 variables. The nomogram achieved areas under the curve of 0.731 and 0.735 for the training and validation cohorts, respectively. The discriminatory ability of the nomogram was further assessed by dividing the cases into three risk groups (low-risk, nomogram score < 175; medium-risk, nomogram score 175~199; high-risk, nomogram score > 199; P < 0.001). Decision curve analysis revealed that the nomogram provided a good net clinical benefit. CONCLUSIONS: We developed a nomogram that could predict postoperative delirium with high accuracy and stability in older patients after major abdominal surgery.

Absolute protein quantification based on calibrated particle counting using electrospray-differential mobility analysis.

The traceability of in vitro diagnostics or drug products is based on the accurate quantification of proteins. In this study, we developed an absolute quantification approach for proteins. This method is based on calibrated particle counting using electrospray-differential mobility analysis (ES-DMA) coupled with a condensation particle counter (CPC). The absolute concentration of proteins was quantified with the observed protein particle number measured with ES-DMA-CPC, and the detection efficiency was determined by calibrators. The measurement performance and quantitative level were verified using two certificated reference materials, BSA and NIMCmAb. The linear regression fit for the detection efficiency values of three reference materials and one highly purified protein (myoglobin, BSA, NIMCmAb and fibrinogen) indicated that the detection efficiency and the particle size distribution of these proteins exhibited a linear relationship. Moreover, to explore the suitability of the detection efficiency-particle size curve for protein quantification, the concentrations of three typical proteinaceous particles, including two high molecular weight proteins (NIST reference material 8671 and D-dimer) and one protein complex (glutathione S-transferase dimer), were determined. This work suggests that this calibrated particle counting method is an efficient approach for nondestructive, rapid and accurate quantification of proteins, especially for measuring proteinaceous particles with tremendous size and without reference standards.

Intelligentization helps the green and energy-saving transformation of power industry-evidence from substation engineering in China.

The coordinated development of intelligence and greening is an intrinsic demand for high-quality economic and social development. Intelligentization and greening are the leading directions of sustainable development of the power industry. This paper directs of sustainable development of the power industry. This paper empirically analyzes the effect and mechanism of intelligence on the green environmental friendliness of electric power substations by using a panel fixed-effects model and instrumental variable regression, using substation engineering data from China southern power grid during 2013-2022. It is found that the level of intelligence significantly promotes the green performance of substation projects, and this conclusion still holds after a series of robustness tests. Intelligence can reduce material waste and pollutant emissions by improving the engineering environmental monitoring capability and the refinement of engineering resource control, thus improving the environmental friendliness of the project. The research in this paper helps to promote the integrated development of intelligent and green power engineering, to better achieve economic and green goals.

Dual function of LapB (YciM) in regulating Escherichia coli lipopolysaccharide synthesis.

Levels of lipopolysaccharide (LPS), an essential glycolipid on the surface of most gram-negative bacteria, are tightly controlled-making LPS synthesis a promising target for developing new antibiotics. Escherichia coli adaptor protein LapB (YciM) plays an important role in regulating LPS synthesis by promoting degradation of LpxC, a deacetylase that catalyzes the first committed step in LPS synthesis. Under conditions where LPS is abundant, LapB recruits LpxC to the AAA+ protease FtsH for degradation. LapB achieves this by simultaneously interacting with FtsH through its transmembrane helix and LpxC through its cytoplasmic domain. Here, we describe a cryo-EM structure of the complex formed between LpxC and the cytoplasmic domain of LapB (LapBcyto). The structure reveals how LapB exploits both its tetratricopeptide repeat (TPR) motifs and rubredoxin domain to interact with LpxC. Through both in vitro and in vivo analysis, we show that mutations at the LapBcyto/LpxC interface prevent LpxC degradation. Unexpectedly, binding to LapBcyto also inhibits the enzymatic activity of LpxC through allosteric effects reminiscent of LpxC activation by MurA in Pseudomonas aeruginosa. Our findings argue that LapB regulates LPS synthesis in two steps: In the first step, LapB inhibits the activity of LpxC, and in the second step, it commits LpxC to degradation by FtsH.

Development of an isotope dilution mass spectrometry assay for the quantification of insulin based on signature peptide analysis.

An isotope dilution mass spectrometry (IDMS) method that involves peptide-based protein analysis was developed to accurately quantify insulin. In this study, a signature peptide (GFFYTPK) obtained from tryptic digestion of insulin was selected as a surrogate for insulin. Then, the optimal conditions for signature peptide analysis through mass spectrometry detection and enzymatic digestion were determined. The analytical performance of this method was assessed and validated using porcine insulin-certified reference material. The linear range of the insulin calibration curve ranged from 0.05 ~ 2 mass ratios, with recoveries ranging from 96.15 to approximately 101.15%. The limit of detection was 0.19 ng/mL, and the limit of quantification was 0.63 ng/mL. The quantitative results corresponded well with a certified value that was obtained from measuring a porcine insulin reference material with amino acid-based IDMS. In addition, the target peptide GFFYTPK can be found in other species of insulin. This method was also applied for the quantification of human insulin-certified reference material. Finally, we applied the method to quantify the concentrations of simulated serum insulin. These findings suggested that this signature peptide-based IDMS approach can accurately quantify insulin levels, can assign a certified value to insulin reference materials, and has the potential to quantify serum insulin with traceable measurements.

Gut microbiota and cognitive performance: A bidirectional two-sample Mendelian randomization.

PURPOSE: Previous studies have suggested a potential association between gut microbiota and neurological and psychiatric disorders. However, the causal relationship between gut microbiota and cognitive performance remains uncertain. METHODS: A two-sample Mendelian randomization (MR) study used SNPs linked to gut microbiota (n = 18,340) and cognitive performance (n = 257,841) from recent GWAS data. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were employed. Heterogeneity was assessed via Cochran's Q test for IVW. Results were shown with funnel plots. Outliers were detected through leave-one-out method. MR-PRESSO and MR-Egger intercept tests were conducted to address horizontal pleiotropy influence. LIMITATIONS: Limited to European populations, generic level, and potential confounding factors. RESULTS: IVW analysis revealed detrimental effects on cognitive perfmance associated with the presence of genus Blautia (P = 0.013, 0.966[0.940-0.993]), Catenibacterium (P = 0.035, 0.977[0.956-0.998]), Oxalobacter (P = 0.043, 0.979[0.960-0.999]). Roseburia (P < 0.001, 0.935[0.906-0.965]), in particular, remained strongly negatively associated with cognitive performance after Bonferroni correction. Conversely, families including Bacteroidaceae (P = 0.043, 1.040[1.001-1.081]), Rikenellaceae (P = 0.047, 1.026[1.000-1.053]), along with genera including Paraprevotella (P = 0.044, 1.020[1.001-1.039]), Ruminococcus torques group (P = 0.016, 1.062[1.011-1.115]), Bacteroides (P = 0.043, 1.040[1.001-1.081]), Dialister (P = 0.027, 1.039[1.004-1.074]), Paraprevotella (P = 0.044, 1.020[1.001-1.039]) and Ruminococcaceae UCG003 (P = 0.007, 1.040[1.011-1.070]) had a protective effect on cognitive performance. CONCLUSIONS: Our results suggest that interventions targeting specific gut microbiota may offer a promising avenue for improving cognitive function in diseased populations. The practical application of these findings has the potential to enhance cognitive performance, thereby improving overall quality of life.

Ceftazidime-avibactam induced renal disorders: past and present.

With the increasing prevalence of multidrug-resistant Gram-negative bacterial pathogens worldwide, antimicrobial resistance has become a significant public health concern. Ceftazidime-avibactam (CAZ-AVI) exhibited excellent in vitro activity against many carbapenemase-producing pathogens, and was widely used for the treatment of various complicated infections. CAZ-AVI is well tolerated across all dosing regimens, and its associated acute kidney injury (AKI) in phase II/III clinical trials is rare. However, recent real-world studies have demonstrated that CAZ-AVI associated AKI was more frequent in real-world than in phase II and III clinical trials, particularly in patients receiving concomitant nephrotoxic agents, with critically ill patients being at a higher risk. Herein, we reviewed the safety data related to renal impairment of CAZ-AVI, and discussed its pharmacokinetic/pharmacodynamic targets and dosage adjustment in patients with impaired renal function. This review aimed to emphasize the importance for healthcare professionals to be aware of this adverse event of CAZ-AVI and provide practical insights into the dosage optimization in critically ill patients with renal dysfunction.

Association of sleep quality on the night of operative day with postoperative delirium in elderly patients: A prospective cohort study.

BACKGROUND: Sleep disturbances in the peri-operative period have been associated with adverse outcomes, including postoperative delirium (POD). However, research on sleep quality during the immediate postoperative period is limited. OBJECTIVES: This study aimed to investigate the association between sleep quality on the night of the operative day assessed using the Sleep Quality Numeric Rating Scale (SQ-NRS), and the incidence of POD in a large cohort of surgical patients. DESIGN: A prospective cohort study. SETTING: A tertiary hospital in China. PATIENTS: This study enrolled patients aged 65 years or older undergoing elective surgery under general anaesthesia. The participants were categorised into the sleep disturbance and no sleep disturbance groups according to their operative night SQ-NRS. MAIN OUTCOME MEASURES: The primary outcome was delirium incidence, whereas the secondary outcomes included acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. RESULTS: In total, 3072 patients were included in the analysis of this study. Among them, 791 (25.72%) experienced sleep disturbances on the night of operative day. Patients in the sleep disturbance group had a significantly higher risk of developing POD (adjusted OR 1.43, 95% CI 1.11 to 1.82, P  = 0.005). Subgroup analysis revealed that age 65-75 years; male sex; ASA III and IV; haemoglobin more than 12 g l -1 ; intra-operative hypotension; surgical duration more than 120 min; and education 9 years or less were significantly associated with POD. No interaction was observed between the subgroups. No significant differences were observed in the secondary outcomes, such as acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. CONCLUSIONS: The poor subjective sleep quality on the night of operative day was independently associated with increased POD risk, especially in certain subpopulations. Optimising peri-operative sleep may reduce POD. Further research should investigate potential mechanisms and causal relationships. TRIAL REGISTRY: chictr.org.cn: ChiCTR1900028545.

The predictive value of sarcopenia and myosteatosis in trans-arterial (chemo)-embolization treated HCC patients.

BACKGROUND: We conducted a meta-analysis to provide evidence-based results for the predictive values of sarcopenia, skeletal muscle index, psoas muscle index and the myosteatosis regarding the impact of survival outcomes and tumor response in patients treated by trans-arterial (chemo)-embolization (TAE/TACE), thereby optimizing therapeutic strategies and maximizing clinical benefits for hepatocellular carcinoma patients. METHODS: Qualified studies were retrieved from PubMed, the Cochrane Library, EMBASE, and Google Scholar before June 19, 2023. We investigated the relationships between sarcopenia, SMI, PMI, myosteatosis, and the overall survival of TAE/TACE-treated hepatocellular carcinoma patients with pooling data. RESULTS: A total of 167 studies were collected and 12 studies were finally included for analysis. The meta-analysis assisted that the sarcopenia (HR: 1.46, 95% CI: 1.30-1.64, p < 0.001), skeletal muscle index (HR: 1.48, 95% CI: 1.29-1.69, p < 0.001), and psoas muscle index (HR: 1.45, 95% CI: 1.19-1.77, p < 0.001) were significantly related to a shorter OS of hepatocellular carcinoma patients who treated by TAE/TACE. Sarcopenia significantly contributed to a lower objective response rate of TAE/TACE treated hepatocellular carcinoma patients (OR: 0.80, 95% CI: 0.65-0.98, p = 0.032). But there was no significant association between the myosteatosis and the overall survival (HR: 1.29, 95% CI: 0.74-2.25, p = 0.366). Sensitivity analysis supported the stability and dependability of above analyses conclusions. CONCLUSION: Sarcopenia, skeletal muscle index and psoas muscle index, are significant prognostic predictors for TAE/TACE treated hepatocellular carcinoma patients. While myosteasis does not demonstrate a prognostic impact on the overall survival of TAE/TACE treated hepatocellular carcinoma patients.

Risk factors prediction of 6-month mortality after noncardiac surgery of older patients in China: a multicentre retrospective cohort study.

BACKGROUND: Identifying the risk factors associated with perioperative mortality is crucial, particularly in older patients. Predicting 6-month mortality risk in older patients based on large datasets can assist patients and surgeons in perioperative clinical decision-making. This study aimed to develop a risk prediction model of mortality within 6 months after noncardiac surgery using the clinical data from 11 894 older patients in China. MATERIALS AND METHODS: A multicentre, retrospective cohort study was conducted in 20 tertiary hospitals. The authors retrospectively included 11 894 patients (aged ≥65 years) who underwent noncardiac surgery between April 2020 and April 2022. The least absolute shrinkage and selection operator model based on linear regression was used to analyse and select risk factors, and various machine learning methods were used to build predictive models of 6-month mortality. RESULTS: The authors predicted 12 preoperative risk factors associated with 6-month mortality in older patients after noncardiac surgery. Including laboratory-associated risk factors such as mononuclear cell ratio and total blood cholesterol level, etc. Also including medical history associated risk factors such as stroke, history of chronic diseases, etc. By using a random forest model, the authors constructed a predictive model with a satisfactory accuracy (area under the receiver operating characteristic curve=0.97). CONCLUSION: The authors identified 12 preoperative risk factors associated with 6-month mortality in noncardiac surgery older patients. These preoperative risk factors may provide evidence for a comprehensive preoperative anaesthesia assessment as well as necessary information for clinical decision-making by anaesthesiologists.

Preoperative prognostic nutritional index predicts postoperative delirium in aged patients after surgery: A matched cohort study.

OBJECTIVE: Prognostic nutritional index (PNI) is an indicator to evaluate the nutritional immune status of patients. This study aimed to assess whether preoperative PNI could predict the occurrence of postoperative POD in aged patients undergoing non-neurosurgery and non-cardiac surgery. METHOD: The aged patients undergoing non-neurosurgery and non-cardiac surgery between January 2014 and August 2019 were included in the retrospective cohort study. The correlation between POD and PNI was investigated by univariate and multivariable logistic regression analysis, propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and subgroup analysis. RESULTS: In the cohort (n = 29,814), the cutoff value of PNI was 46.01 determined by the receiver operating characteristic (ROC) curve. In univariate and three multivariable regression analysis, the ORs of PNI ≤ 46.01 was 2.573(95% CI:2.261-2.929, P < 0.001),1.802 (95% CI:1.567-2.071, P < 0.001),1.463(95% CI:1.246-1.718, P < 0.001),1.370(95% CI:1.165-1.611, P < 0.001). In the PSM model and IPTW model, the ORs of PNI ≤ 46.01 were 1.424(95% CI:1.172-1.734, P < 0.001) and 1.356(95% CI:1.223-1.505, P < 0.001). CONCLUSION: The PNI was found to have a predictive value for POD in patients undergoing non-neurosurgery and non-cardiac surgery. Improving preoperative nutritional status may be beneficial in preventing POD for aged patients.

Development of cancer biomarker heat shock protein 90α certified reference material using two different isotope dilution mass spectrometry techniques.

Heat shock protein 90α (HSP90α) has been regarded as an important indicator for judging tumor metastasis and prognosis due to its significant upregulation in various tumors. Therefore, the accurate quantification of HSP90α is of great significance for clinical diagnosis and therapy of cancers. However, the lack of HSP90α certified reference material (CRM) leads to the accuracy and consistency of quantification methods not being effectively evaluated. Besides, quantitative results without traceability make comparisons between different studies difficult. In this study, an HSP90α solution CRM was developed from the recombinant protein raw material. The recombinant protein is a dimer, and the purity of the CRM candidate reached 96.71%. Both amino acid analysis-isotope dilution mass spectrometry (AAA-IDMS) and unique peptide analysis-isotope dilution mass spectrometry (UPA-IDMS) were performed to measure the content of HSP90α in the solution CRM candidate, and the certified value was assessed to be 66.2 ± 8.8 µg/g. Good homogeneity of the CRM was identified, and the stability examination suggested that the CRM was stable for at least 4 months at - 80 °C and for 7 days at 4 °C. With traceability to SI unit (kg), this CRM has potential to help establish a metrological traceability chain for quantification of HSP90α, which will make the quantification results standardized and comparable regardless of the quantitative methods.

Effectiveness and safety of second-generation antipsychotics for psychiatric disorders apart from schizophrenia: A systematic review and meta-analysis.

Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient.

Mental health changes in elderly patients undergoing non-cardiac surgery during the COVID-19 pandemic in China.

BACKGROUND: The COVID-19 pandemic has a heavy impact on the mental health of elderly surgical patients worldwide. In particular, the elderly patients faced considerable psychological stress due to various environmental and medical factors during the outbreak. This study aims to examine changes in mental health trends among non-cardiac surgical patients aged 65 and above in China during the COVID-19 pandemic. METHODS: This multi-center, convenient sampling, longitudinal observational study was conducted from April 1, 2020 to April 30, 2022. Primary outcome was the prevalence of postoperative depression. Secondary outcome was the prevalence of postoperative anxiety. Follow-up was conducted separately at 7 days and 30 days after surgery. Depression symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9) scale. Anxiety symptoms were assessed using Generalized Anxiety Disorder-7 (GAD-7) scale, with scores of ≥5 defining positive depression or anxiety symptoms. Multivariate logistic regression analysis was used to investigate risk factors of mental health status in more elderly patients undergoing non-cardiac surgery. RESULTS: A total of 4639 patients were included, of whom 2279 (46.0 %) were male, 752 (15.2 %) were over the age of 75, and 4346 (93.7 %) were married. The monthly prevalence trends demonstrated that compared to the outbreak period, a significant reduction in the prevalence of depression and anxiety symptoms in elderly patients who underwent surgery during the post-pandemic period. In post-pandemic period, a statistically significant decrease in the prevalence of all severity depression and anxiety patients was noted at the 7-day follow-up, but no significant decrease was observed for severe depression and anxiety in the 30-day follow-up. In COVID-19 low-risk area, a significant overall decrease in prevalence of mental health was observed during the post-pandemic period compared to the outbreak period, including 7-day depression, 7-day anxiety, 30-day depression, and 30-day anxiety (all with P < 0.001). Female and patients with ≥2 comorbidities appeared to be more susceptible to postoperative depression and anxiety during the pandemic. LIMITATION: The absence of data from the early days of the COVID-19 outbreak. CONCLUSIONS: This study analyzed the prevalence of depression and anxiety in elderly non-cardiac patients during and after the COVID-19 pandemic, focusing on dimensions such as severity, risk-areas, gender, and comorbidity. Our findings revealed a significant decrease in the prevalence of depression and anxiety in elderly surgery patients during the post-pandemic period.