Associations of toxic metals and their mixture with hyperuricemia in Chinese rural older adults.

Previous studies have related single toxic metals (TMs) to hyperuricemia (HUA) among the general population, however, the association of the TM mixture with HUA, especially in older adults, remains poorly understood. We aimed to examine the relationships between individual TMs and their mixture and HUA in Chinese rural older adults. This study consisted of 2075 rural older adults aged 60 years or over. Blood concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), gallium (Ga), mercury (Hg), lead (Pb), thallium (Tl), and uranium (U) were detected using inductively coupled plasma mass spectrometry. The associations of single TMs with HUA were assessed using logistic regression and restricted cubic spline (RCS) models, and the association of TM mixture with HUA was explored using the elastic net with environmental risk score (ENET-ERS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR) models, respectively. Adjusted logistic regression model showed that Cs (OR = 1.65, 95% CI 1.37-1.99) and Pb (OR = 1.46, 95% CI 1.28-1.67) were positively related to HUA, and RCS model exhibited a positive linear association of Cs and Pb with HUA. ENET-ERS and QGC models quantified a positive correlation between the TM mixture and the odds of HUA, with estimated ORs of 1.15 (95% CI 1.11-1.19) and 1.84 (95% CI 1.37-2.47), respectively, and Cs and Pb had the most weight. BKMR model demonstrated a significant linear association between the TM mixture and increased odds of HUA, with the posterior inclusion probabilities (PIPs) of both Cs and Pb being 1.00. Moreover, we observed a positive interaction between Cs and Pb on HUA. The TM mixture is associated with increased odds of HUA in rural older adults, which may mainly be driven by Cs and Pb. Subsequent studies are warranted to confirm these findings and clarify the mechanisms linking multiple TMs with HUA.

An updated patent review of stimulator of interferon genes agonists (2021 - present).

INTRODUCTION: Stimulator of Interferon Genes (STING) is an innate immune sensor. Activation of STING triggers a downstream response that results in the expression of proinflammatory cytokines (TNF-α, IL-1ß) via nuclear factor kappa-B (NF-κB) or the expression of type I interferons (IFNs) via an interferon regulatory factor 3 (IRF3). IFNs can eventually result in promotion of the adaptive immune response including activation of tumor-specific CD8+ T cells to abolish the tumor. Consequently, activation of STING has been considered as a potential strategy for cancer treatment. AREAS COVERED: This article provides an overview on structures and pharmacological data of CDN-like and non-nucleotide STING agonists acting as anticancer agents (January 2021 to October 2023) from a medicinal chemistry perspective. The data in this review come from EPO, WIPO, RCSB PDB, CDDI. EXPERT OPINION: In recent years, several structurally diverse STING agonists have been identified. As an immune enhancer, they are used in the treatment of tumors, which has received extensive attention from scientific community and pharmaceutical companies. Despite the multiple challenges that have appeared, STING agonists may offer opportunities for immunotherapy.

Melatonin improves maternal sleep deprivation-induced learning and memory impairment, inflammation, and synaptic dysfunction in murine male adult offspring.

INTRODUCTION: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown. METHODS: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting. RESULTS: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels. CONCLUSIONS: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.

Mitochondrial antioxidant elamipretide improves learning and memory impairment induced by chronic sleep deprivation in mice.

BACKGROUND: The inflammation and synaptic dysfunction induced by mitochondrial dysfunction play essential roles in the learning and memory impairment associated with sleep dysfunction. Elamipretide (SS-31), a novel mitochondrion-targeted antioxidant, was proven to improve mitochondrial dysfunction, the inflammatory response, synaptic dysfunction, and cognitive impairment in models of cerebral ischemia, sepsis, and type 2 diabetes. However, the potential for SS-31 to improve the cognitive impairment induced by chronic sleep deprivation (CSD) and its underlying mechanisms is unknown. METHODS: Adult c57BL/6J mice were subjected to CSD for 21 days using an activity wheel accompanied by daily intraperitoneal injection of SS-31 (5 mg/kg). The novel object recognition and Morris water maze test were used to evaluate hippocampus-dependent cognitive function. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to determine the effects of CSD and SS-31 on markers of mitochondria, inflammation response, and synaptic function. Enzyme-linked immunosorbent assays were used to examine the levels of proinflammatory cytokines. RESULTS: SS-31 could improve the cognitive impairment induced by CSD. In particular, SS-31 treatment restored the CSD-induced decrease in sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator alpha levels and the increase in levels nuclear factor kappa-B and inflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha. Furthermore, SS-31 significantly increased the levels of brain-derived neurotrophic factor, postsynaptic density protein-95, and synaptophysin in CSD mice. CONCLUSION: Taken together, these results suggest that SS-31 could improve CSD-induced mitochondrial biogenesis dysfunction, inflammatory response, synaptic dysfunction, and cognitive impairment by increasing SIRT1 expression levels.

The underlying neuropsychological and neural correlates of the impaired Chinese reading skills in children with attention deficit hyperactivity disorder.

Impaired basic academic skills (e.g., word recognition) are common in children with Attention Deficit Hyperactivity Disorder (ADHD). The underlying neuropsychological and neural correlates of impaired Chinese reading skills in children with ADHD have not been substantially explored. Three hundred and two children with ADHD (all medication-naïve) and 105 healthy controls underwent the Chinese language skill assessment, and 175 also underwent fMRI scans (84 ADHD and 91 controls). Between-group and mediation analyses were applied to explore the interrelationships of the diagnosis of ADHD, cognitive dysfunction, and impaired reading skills. Five ADHD-related brain functional networks, including the default mode network (DMN) and the dorsal attention network (DAN), were built using predefined regions of interest. Voxel-based group-wise comparisons were performed. The ADHD group performed worse than the control group in word-level reading ability tests, with lower scores in Chinese character recognition (CR) and word chains (WS) (all P < 0.05). With full-scale IQ and sustained attention in the mediation model, the direct effect of ADHD status on the CR score became insignificant (P = 0.066). The underlying neural correlates for the orthographic knowledge (OT) and CR differed between the ADHD and the control group. The ADHD group tended to recruit more DMN regions to maintain their reading performance, while the control group seemed to utilize more DAN regions. Children with ADHD generally presented impaired word-level reading skills, which might be caused by impaired sustained attention and lower IQ. According to the brain functional results, we infer that ADHD children might utilize a different strategy to maintain their orthographic knowledge and character recognition performance.

Relationship of solid fuels use with cognitive function and efficacy of switching to cleaner fuels or using ventilation: A systematic review and meta-analysis.

BACKGROUND: A growing number of studies have examined the relation between solid fuels use and cognitive function in the mid-elderly, but results are inconsistent. Therefore, a systematic review and meta-analysis was carried out to evaluate their relevance and the efficacy of switching to cleaner fuels or using ventilation. METHOD: We used PubMed, Web of Science, and Cochrane Library databases to identify 17 studies in which the primary outcome variable was cognitive function decline or cognitive disorders, and the exposure measure was solid fuels use. The final search date of August 31, 2023. The effect size of odds ratio (OR), regression coefficient (ß), and 95% confidence interval (CI) were pooled. Heterogeneity and the possibility of publication bias were assessed by using the Q-statistic and Begg's test, respectively. RESULT: Among the 17 included papers, the study participants were ≥45 years old. Eleven studies assessed the relationship between solid fuels use and cognitive function decline [number of studies (n) = 11, ß = -0.144; I2 = 97.7%]. Five studies assessed the relationship between solid fuels use and cognitive disorders (n = 5, OR = 1.229; I2 = 41.1%). Switching from using solid fuels to clean fuels could reduce the risk of cognitive function decline as compared to those who remained on using solid fuels (n = 2; ß = 0.710; I2 = 82.4%). Among participants using solid fuels, who cooked without on ventilated stoves were correlated with an enhanced risk of cognitive disorders as compared to participants who cooked with ventilated stoves (n = 2; OR = 1.358; I2 = 44.7%). CONCLUSION: Our meta-analysis showed a negative relationship between solid fuels use with cognitive function, and a positive relationship with cognitive disorders. Cleaner fuels, using ventilation, improved cookstoves can reduce the adverse health hazards of solid fuels use.

An enriched environment ameliorates maternal sleep deprivation-induced cognitive impairment in aged mice by improving mitochondrial function via the Sirt1/PGC-1α pathway.

BACKGROUND: Early life stress can cause cognitive impairment in aged offspring. Environmental enrichment (EE) is considered to be an effective non-pharmacological treatment for improving cognitive decline. The aim of this research was to evaluate the effect of EE, on cognitive impairment in aged offspring induced by maternal sleep deprivation (MSD) and the underlying mechanisms involved to investigate its potential value in clinical practice. METHODS: CD-1 damns were subjected or not to sleep deprivation during late gestation. Twenty-one days after birth, the offspring were assigned to standard or EE cages. At 18 months-old, the learning and memory function of the offspring mice was evaluated using Morris water maze. The hippocampal and prefrontal cortical levels of protein, gene, proinflammation cytokines, and oxidative stress indicators was examined by Western blot, real-time polymerase chain reaction, enzyme linked immunosorbent assay, and biochemical assays. RESULTS: Offspring in MSD group exhibited declined learning and memory abilities compared with control animals. Moreover, the hippocampal and prefrontal cortical levels of Sirtuin1 (Sirt1), peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), postsynaptic density protein-95, and synaptophysin were lower and those of proinflammation cytokines higher in the MSD group; meanwhile, the superoxide dismutase content was higher and the malondialdehyde and reactive oxygen species contents were lower. However, these deleterious changes were ameliorated by exposure to EE. CONCLUSIONS: EE attenuates MSD-induced cognitive impairment, oxidative stress, and neuroinflammation and reverses the reduction in synaptic protein levels in aged offspring mice via the Sirt1/PGC-1α pathway.

Increased cysteinyl-tRNA synthetase drives neuroinflammation in Alzheimer's disease.

BACKGROUND: Microglia-mediated neuroinflammation in Alzheimer's disease (AD) is not only a response to pathophysiological events, but also plays a causative role in neurodegeneration. Cytoplasmic cysteinyl-tRNA synthetase (CARS) is considered to be a stimulant for immune responses to diseases; however, it remains unknown whether CARS is involved in the pathogenesis of AD. METHODS: Postmortem human temporal cortical tissues at different Braak stages and AD patient-derived serum samples were used to investigate the changes of CARS levels in AD by immunocytochemical staining, real-time PCR, western blotting and ELISA. After that, C57BL/6J and APP/PS1 transgenic mice and BV-2 cell line were used to explore the role of CARS protein in memory and neuroinflammation, as well as the underlying mechanisms. Finally, the associations of morphological features among CARS protein, microglia and dense-core plaques were examined by immunocytochemical staining. RESULTS: A positive correlation was found between aging and the intensity of CARS immunoreactivity in the temporal cortex. Both protein and mRNA levels of CARS were increased in the temporal cortex of AD patients. Immunocytochemical staining revealed increased CARS immunoreactivity in neurons of the temporal cortex in AD patients. Moreover, overexpression of CARS in hippocampal neurons induced and aggravated cognitive dysfunction in C57BL/6J and APP/PS1 mice, respectively, accompanied by activation of microglia and the TLR2/MyD88 signaling pathway as well as upregulation of proinflammatory cytokines. In vitro experiments showed that CARS treatment facilitated the production of proinflammatory cytokines and the activation of the TLR2/MyD88 signaling pathway of BV-2 cells. The accumulation of CARS protein occurred within dense-core Aß plaques accompanied by recruitment of ameboid microglia. Significant upregulation of TLR2/MyD88 proteins was also observed in the temporal cortex of AD. CONCLUSIONS: The findings suggest that the neuronal CARS drives neuroinflammation and induces memory deficits, which might be involved in the pathogenesis of AD.

Sarcopenia predicts postoperative complications and survival in colorectal cancer patients with GLIM-defined malnutrition: Analysis from a prospective cohort study.

OBJECTIVE: To investigate whether sarcopenia could predict postoperative outcomes in patients with colorectal cancer with Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition. METHODS: Clinical data of patients who underwent radical resection for colorectal cancer were prospectively collected. Sarcopenia was diagnosed by the combination of low handgrip strength and low muscle quantity or quality as measured by abdominal computed tomography (CT) images. Logistic regression analysis and Cox proportional hazards regression analysis were performed to identify independent predictors for postoperative complications and survival, respectively. RESULTS: A total of 310 patients with colorectal cancer with GLIM-defined malnutrition were included, of which 145 (46.77%) were identified with sarcopenia. Malnutritional patients with sarcopenia had significantly higher incidences of total complications (34.5% versus 15.8%), severe complications (9.7% versus 1.8%), longer lengths of postoperative hospital stay (median, 14 days versus 12 days), and more costs (median, 56,257 RMB versus 49,024 RMB) than those without sarcopenia. Sarcopenia was an independent predictive factor for postoperative complications (OR 2.531, 95% CI 1.451-4.415), overall survival (HR 1.519, 95% CI 1.026-2.248), and disease-free survival (HR 1.847, 95% CI 1.324-2.576). Patients with severe sarcopenia had a higher incidence of severe complications but not total complications or survival than those with not-severe sarcopenia. Moreover, the predictive value of sarcopenia for postoperative complications was attributed to muscle strength and quality but not muscle quantity. CONCLUSION: Sarcopenia predicts postoperative complications and survival in patients with colorectal cancer with GLIM-defined malnutrition. Preoperative assessment of sarcopenia is still necessary when nutritional assessment has been well performed.

Long-term environmental enrichment overcomes depression, learning, and memory impairment in elderly CD-1 mice with maternal sleep deprivation exposure.

Early-life stress disrupts central nervous system development and increases the risk of neuropsychiatric disorder in offspring based on rodent studies. Maternal sleep deprivation (MSD) in rodents has also been associated with depression and cognitive decline in adult offspring. However, it is not known whether these issues persist into old age. Environmental enrichment is a non-pharmacological intervention with proven benefits in improving depression and cognitive impairment; however, it is unclear whether these benefits hold for aging mice following MSD exposure. The aim of this study was to explore the effects of MSD on depression and cognition in elderly offspring CD-1 mice and to determine whether long-term environmental enrichment could alleviate these effects by improving neuroinflammation and synaptic plasticity. The offspring mice subjected to MSD were randomly assigned to either a standard environment or an enriched environment. At 18 months of age, the forced swimming and tail suspension tests were used to evaluated depression-like behaviors, and the Morris water maze test was used to evaluate cognitive function. The expression levels of hippocampal proinflammatory cytokines and synaptic plasticity-associated proteins were also measured. MSD increased depression-like behaviors and impaired cognition function in aging CD-1 offspring mice. These effects were accompanied by upregulated interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α expression, and downregulated brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density-95, and synaptophysin expression in the hippocampus. All of these changes were reversed by long-term exposure to an enriched environment. These findings suggest that MSD exerts long-term effects on the behaviors of offspring in mice, leading to depression and cognitive impairment in older age. Importantly, long-term environmental enrichment could counteract the behavior difficulties induced by MSD through improving hippocampal proinflammatory cytokines and synaptic plasticity-associated proteins.

Predation preference for extracellular polysaccharides by paramecia and rotifers may have accelerated the decline of membrane biofilm hydraulic resistance.

The hydraulic resistance of biofilm layer on membranes impacts the filtration resistance significantly. The effect of predation by two model microfauna (i.e., paramecia and rotifers) on the hydraulic resistance, structure, extracellular polymeric substance (EPS), and bacterial community of biofilms developed on supporting materials (i.e., nylon mesh) was evaluated in this study. Long-term experiments demonstrated that predation could alter biofilm compositions and accelerated the decline of hydraulic resistance by increasing biofilm heterogeneity and deformation. Importantly, predation preference of paramecia and rotifers on biofilm components were further investigated for the first time by tracking the fluorescence change in the predator bodies after exposure to the stained biofilms. Results indicated that after 12-hour's incubation, the ratio of extracellular α-polysaccharides (α-PS) to proteins (PN) within the bodies of paramecia and rotifers increased to 2.6 and 3.9, respectively, which was 0.76 in the original biofilms. The ratios of α-PS/live cells within paramecia and rotifers increased to 1.42 and 1.64 from 0.81 in the original biofilms. The ratio of live/dead cells in the predator bodies, however, changed slightly compared to the original biofilms. These results clearly and directly evidenced that both paramecia and rotifers could feed on biofilm EPS and cells, but having a significant preference for PS over PN and cells. Since extracellular PS is recognized as a primary biofilm adhesion agent, the preference for PS could better explain why predation had accelerated the disintegration and hydraulic resistance decline of mesh biofilms.

Influence of different factors on registration error in a 1.5 T MR-guided linac.

Purpose. Accurate image registration is an important step in online image-guided adaptive radiotherapy. The aim of this study was to investigate the effects of different factors on registration accuracy in a magnetic resonance (MR)-guided adaptive radiotherapy workflow.Materials and Methods. A thorax motion phantom was used to obtain computed tomography (CT) simulations in 8 different motion modes and to generate 8 reference plans. Daily pretreatment online MR images were obtained at 5 different positions in each reference plan. Online MR and CT simulations were separately registered using bone structures and the gross tumor volume (GTV) as ROIs, and the image shift distance was recorded by the online treatment planning system. The difference between the shift distance and the real isocentric distance was the registration error. The registration error was analyzed, and the effects of the setup position, motion mode and ROI selection on the registration error were investigated by multivariate analysis of variance.Result. The minimum values of registration error (ΔX, ΔY, ΔZ) were -1.90 mm, -2.70 mm and -2.40 mm, respectively, and the maximum values were 1.70 mm, 4.30 mm and -0.90 mm. ΔY showed the maximum mean standard deviation of 1.25 mm, and ΔZshowed the minimum mean standard deviation of 0.27 mm. The standard deviation of the registration error is largest in the inferior/superior direction. The motion mode of the phantom and ROI selection were significantly correlated with ΔX, ΔY, and ΔZ(p< 0.05).Conclusion. The registration result with the spine as the selected ROI was better than that with the GTV as the ROI. In 1.5 T MR-linac clinical treatment, more attention should be given to patient movement repeatability and to controlling the intrafractional motion as much as possible. It is not recommended to make the GTV-PTV margin expansion less than 2 mm for MR-linac.

Differential metabolites in cirrhotic patients with hepatitis B and muscle mass loss.

Background: Sarcopenia leads to complications (infections, hepatic encephalopathy and ascites) and poor overall survival in patients with cirrhosis, in which the phenotypic presentation is loss of muscle mass. This study aimed to reveal the metabolic profile and identify potential biomarkers in cirrhotic patients with hepatitis B virus and muscle mass loss. Method: Twenty decompensated cirrhotic patients with HBV and muscle mass loss were designated Group S; 20 decompensated cirrhotic patients with HBV and normal muscle mass were designated Group NS; and 20 healthy people were designated Group H. Muscle mass loss was defined as the skeletal muscle mass index less than 46.96 cm2/m2 for males and less than 32.46 cm2/m2 for females. Gas chromatography-mass spectrometry was used to explore the distinct metabolites and pathways in the three groups. Results: Thirty-seven metabolic products and 25 associated metabolic pathways were significantly different in the Group S patients from Group NS patients. Strong predictive value of 11 metabolites (inosine-5'-monophosphate, phosphoglycolic acid, D-fructose-6-phosphate, N-acetylglutamate, pyrophosphate, trehalose-6-phosphate, fumaric acid, citrulline, creatinine, (r)-3-hydroxybutyric acid, and 2-ketobutyric acid) were selected as potential biomarkers in Group S patients compared with Group NS patients. Two pathways may be associated with loss of muscle mass in patients with liver cirrhosis: amino acid metabolism and central carbon metabolism in cancer. Conclusion: Seventy differential metabolites were identified in patients who have liver cirrhosis and loss of muscle mass compared with patients who have cirrhosis and normal muscle mass. Certain biomarkers might distinguish between muscle mass loss and normal muscle mass in HBV-related cirrhosis patients.

Imidazo[1,2-a]Pyridine Derivatives as Novel Dual-Target Inhibitors of ABCB1 and ABCG2 for Reversing Multidrug Resistance.

ABCB1 and ABCG2 are the important ATP-binding cassette (ABC) transporters associated with multidrug resistance (MDR). Herein, we designed a series of imidazo[1,2-a]pyridine derivatives as dual-target inhibitors of ABCB1 and ABCG2 through the scaffold hopping strategy. Compound Y22 displayed potential efflux function inhibitory toward both ABCB1 and ABCG2 (reversal fold: ABCB1 = 8.35 and ABCG2 = 2.71) without obvious cytotoxicity. Y22 also enhanced the potency of antiproliferative drugs in vitro. Mechanistic studies demonstrated that Y22 slightly suppressed ATPase activity but did not affect the protein expression of ABCB1 or ABCG2. Notably, Y22 exhibited negligible CYP3A4 inhibition and enhanced the antiproliferative activity of adriamycin in vivo by restoring the sensitivity of resistant cells. Thus, Y22 may be effective clinically in combination with common chemotherapy agents. In summary, Y22 is a potential dual-target inhibitor that reverses MDR by blocking the efflux function of ABCB1 and ABCG2.

Gender-and age-specific associations of sleep duration and quality with cognitive impairment in community-dwelling older adults in Anhui Province, China.

Objective: To examine associations of sleep duration and quality with cognitive impairment in older adults and the moderating role of gender and age in these associations. Methods: This community-based cross-sectional study included 4,837 participants aged 60 years and above. Cognitive function was assessed using the Chinese version of the Mini-Mental State Examination (MMSE), and the participants were grouped based on the presence of cognitive impairment. The duration and quality of sleep were assessed using the Pittsburgh Sleep Quality Index (PSQI). Multivariate logistic regression models were used to analyze associations of sleep duration and quality with cognitive impairment. The role of age and gender in these associations have also been explored. Results: The age (mean ± SD) of the participants was 71.13 ± 5.50 years. Of all older adults, 1,811 (37.44%) were detected as cognitive impairment, and 1755 (36.8%) had poor sleep quality. Among those with cognitive impairment, 51.09% were female. The proportion of the participants with cognitive impairment is significantly higher in those with symptoms of depression (49.73%, 273/549) (χ2 = 41.275, p < 0.001) than in those without depressive symptoms. After adjustment for multiple confounding factors and the crucial covariate (depressive symptoms), the odds ratios (OR) (95% confidence interval [CI]) of cognitive impairment (with 7-7.9 h regarded as the reference group) for individuals with a sleep duration of <6, 6-6.9, 8-8.9, and ≥ 9 h were 1.280 (1.053-1.557), 1.425 (1.175-1.728), 1.294 (1.068-1.566), and 1.360 (1.109-1.668), respectively. Subgroup analysis showed a V-shaped association between night sleep duration and cognitive impairment in males (p ≤ 0.05), and the association was stronger for individuals aged 60-80 years. With regard to sleep quality, the fully adjusted OR (95%CI) of cognitive impairment were 1.263 (1.108-1.440). According to scores of subscales in the PSQI, daytime dysfunction was associated with an increased risk of cognitive impairment (OR: 1.128, 95%CI: 1.055-1.207). Subgroup analysis also revealed a statistically significant correlation between poor sleep quality (including daytime dysfunction) and cognitive impairment in different gender and age groups, with the association being stronger in females (OR: 1.287, 95%CI: 1.080-1.534) and those aged 81-97 years (OR: 2.128, 95%CI: 1.152-3.934). For cognitive impairment, the group aged 81-97 years with daytime dysfunction was associated with a higher odds ratio than other age groups. Conclusion: The present study showed that inadequate or excessive sleep was associated with cognitive impairment, especially in males, who exhibited a V-shaped association. Cognitive impairment was also associated with poor sleep quality as well as daytime dysfunction, with females and individuals aged 81-97 years exhibiting the strongest association.

Prognostic Significance of the Systemic Immune-Inflammation Index in Patients With Cholangiocarcinoma: A Meta-Analysis.

Background: The systemic immune-inflammation index (SII) is a significant prognostic factor for neoplastic diseases. However, the prognostic value of SII in patients with cholangiocarcinoma (CCA) remains unclear. This meta-analysis aimed to investigate the prognostic value of preoperative SII in patients with CCA. Method: We systematically searched for relevant studies in PubMed, Scopus, EMBASE, Web of Science, PROSPERO, and Cochrane Library databases up to March 22, 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the association between SII and survival outcomes, including overall survival (OS) and recurrence-free survival. Results: Five studies with 1402 patients were included in this meta-analysis to determine the prognostic value of preoperative SII. The results showed that a higher SII was associated with poor OS in patients with CCA who underwent invasive surgery (HR=1.916; 95% CI, 1.566-2.343; Z=6.329; P<0.001). The results were reliable in the subgroup analysis according to country, age, sample size, SII cutoff values, and treatment methods. Conclusions: A high preoperative SII appears to be an effective and practical method for monitoring survival in patients with CCA. Systematic Review Registration: International Platform of Registered Systematic. Review and Meta-Analysis Protocols (INPLASY), identifier INPLASY202240015.

[Quality value transfer of substance benchmarks in Sanpian Decoction].

According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.

Robustness and reproducibility of radiomics in T2 weighted images from magnetic resonance image guided linear accelerator in a phantom study.

PURPOSE: Quantitative radiomics features extracted from medical images have been shown to provide value in predicting clinical outcomes. The study for robustness and reproducibility of radiomics features obtained with magnetic resonance image guided linear accelerator (MR-Linac) is insufficient. The objective of this work was to investigate the stability of radiomics features extracted from T2-weighted images of MR-Linac for five common effect factors. MATERIALS AND METHOD: In this work, ten jellies, five fruits/vegetables, and a dynamic phantom were used to evaluate the impact of test-retest, intraobserver, varied thicknesses, radiation, and motion. These phantoms were scanned on a 1.5 T MRI system of MR-Linac. For test-retest data, the phantoms were scanned twice with repositioning within 15 min. To assess for intraobserver comparison, the segmentation of MR images was repeated by one observer in a double-blind manner. Three slice thicknesses (1.2 mm, 2.4 mm, and 4.8 mm) were used to select robust features that were insensitive to different thicknesses. The effect of radiation on features was studied by acquiring images when the beam was on. Common movement images of patients during radiotherapy were simulated by a dynamic phantom with five motion states to study the motion effect. A total of 1409 radiomics features, including shape features, first-order features, and texture features, were extracted from the original, wavelet, square, logarithmic, exponential and gradient images. The robustness and reproducibility features were evaluated using the concordance correlation coefficient (CCC). RESULT: The intraobserver group had the most robust features (936/1079, 86.7%), while the group of motion effects had the lowest robustness (56/936, 6.0%), followed by the group of different thickness cohorts (374/936, 40.0%). The stability of features in the test-retest and radiation groups was 1072 of 1312 (81.7%) and 810 of 936 (86.5%), respectively. Overall, 25 of 1409 (2.4%) radiomics features remained robust in all five tests, mostly focusing on the image type of the wavelet. The number of stable features extracted from when the beam was on was less than that extracted when the beam was off. Shape features were the most robust of all of the features in all of the groups, excluding the motion group. CONCLUSION: Compared with other factors fewer features remained robust to the effect of motion. This result emphasizes the need to consider the effect of respiration motion. The study for T2-weighted images from MR-Linac under different conditions will help us to build a robust predictive model applicable for radiotherapy.

[Application progress on taste evaluation methods for oral preparations].

Taste is an important factor affecting the medicinal properties of oral preparations and patient compliance with medication, and also an important evaluation index for oral preparation design and clinical application. How to characterize the taste objectively, accurately, simply, and efficiently is a bottleneck problem that restricts the taste design, development, and utilization of oral preparations. At present, the commonly used taste assessment methods for oral preparations are traditional human taste panel, electronic tongue, animal preference test, in vitro release study, and electrophysiological test. The traditional human taste panel is the first choice for taste evaluation, but it is limited by poor subjectivity and reproducibility. Therefore, despite some limitations, the other four taste assessment methods have been applied in the pharmaceutical industry as auxiliary methods. This study reviewed the detection principles, applicability, advantages, and disadvantages of the above methods to provide references for the taste correction research and taste assessment of oral preparations, improve patient compliance and the competitiveness of oral preparation products in the industry, and promote the development of oral preparation technologies.

The predictive value of revised diastolic dysfunction in outcomes of liver transplantation: A propensity score matching analysis.

Background: Diastolic dysfunction (DD), one of the earliest signs of cirrhotic cardiomyopathy (CCM), is included in the revised 2019 CCM criteria. Nonetheless, relevant research regarding the effects of revised DD on post-liver transplantation (LT) outcomes remains limited. Methods: This retrospective study enrolled patients who underwent LT for decompensated cirrhosis, from January 2018 to March 2021. Patients were divided into DD and non-DD groups. Clinical data were collected. Patients were followed up with, for at least 1 year post-LT; cardiovascular adverse events (AEs) and survival status were recorded. Risk factors were identified using 1:2 propensity score matching (PSM), after adjusting for confounding factors. The caliper value was set to 0.02. Results: Of 231 patients, 153 were diagnosed with DD (male, 81.8%; mean age, 51.5 ± 9.5 years). Nineteen patients with DD died within 1 year, post-LT. After PSM, 97 and 60 patients were diagnosed with and without DD, respectively. Patients with DD had longer intensive care unit (ICU) stays, higher perioperative cardiovascular AEs, and higher mortality rates than those without DD. In a multivariate analysis, interventricular septum (IVS), left atrial volume index (LAVI), and potassium levels were independent prognostic factors of perioperative cardiovascular AEs, while a decreased early diastolic mitral annular tissue velocity (e'), increased neutrophil-to-lymphocyte ratio (NLR) and tumor markers were predictors of mortality within 1 year post-LT after PSM (P < 0.05). Conclusion: Cardiac DD may contribute to perioperative cardiovascular AEs and mortality post-LT. Clinicians should be aware of decompensated cirrhosis in patients with DD.