Effect of Sarcopenia on 10-Year Risk of Atherosclerotic Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus.

Objective: To investigate the impact of sarcopenia on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with type 2 diabetes mellitus (T2DM). Methods: This study included the clinical, laboratory, and body composition data of 1491 patients with T2DM who were admitted to the Department of Endocrinology and Metabolism at Tianjin Union Medical Center from July 2018 to July 2023. The China-PAR model was utilized to evaluate cardiovascular disease risk. Associations between ASCVD risk and various clinical parameters were analyzed, and the relationship between body composition parameters and ASCVD risk was assessed using logistic regression. Results: The analysis revealed that T2DM patients with sarcopenia had a higher 10-year ASCVD risk compared to those without sarcopenia, with reduced muscle mass independently predicting an increased risk of cardiovascular disease. This association was significant among female T2DM patients, while male T2DM patients with sarcopenia showed a marginally higher median ASCVD risk compared to their non-sarcopenic counterparts. ASCVD risk inversely correlated with body muscle parameters and positively correlated with fat content parameters. Specifically, height- and weight-adjusted fat mass (FM, FM%, FMI) were identified as risk factors for ASCVD. Conversely, muscle parameters adjusted for weight and fat (ASM%, SMM%, FFM%, ASM/FM, SMM/FM, FMM/FM) were protective against ASCVD risk. These findings highlight the critical role of sarcopenia in influencing cardiovascular disease risk among Chinese patients with T2DM, as predicted by the China-PAR model. Conclusion: This study highlights the importance of sarcopenia in T2DM patients, not only as an indicator of ASCVD risk, but possibly as an independent risk factor in this demographics.

The impact of dietary acid load on super-agers with exceptional cognitive abilities: a propensity score analysis of national health and nutrition examination survey (NHANES) 2011-2014.

OBJECTIVES: 'Super-agers,' individuals over 80 with memory abilities comparable to those 20-30 years younger. The relationship between super-agers and dietary acid load (DAL) is an area that warrants further investigation. We aim to examine the link between DAL and super-agers and assess DAL's effects on cognitive functions across different age groups and cognitive domains. DESIGN: Employing a cross-sectional analysis of the 2011-2014 National Health and Nutrition Examination Survey (NHANES) data, we utilized propensity score analysis and multivariate-adjusted regression to mitigate confounding factors. SETTING: Older adults aged 60 and above in the United States. PARTICIPANTS: Our primary analysis encompassed 985 older adults, supplemented by a sensitivity analysis with 2,522 participants. MEASUREMENTS: DAL was assessed through potential renal acid load (PRAL), estimated net acid excretion (NAEes), and net endogenous acid production (NEAP) indices. RESULTS: Super-agers demonstrate a preference for alkaline diets, shown by their lower DAL indices. After inverse probability of treatment weighting (IPTW), multivariate-adjusted logistic regression reveals that each unit reduction in NAEes and PRAL increases the chances of being a super-ager by 3.9% and 3.0%, respectively. The DAL's impact on cognitive function becomes more pronounced with age. Lower PRAL and NAEes scores are significantly linked to higher situational memory and overall cognitive performance scores in those over 70, with these effects being even more pronounced in participants over 80. CONCLUSION: This research pioneers in demonstrating that super-agers prefer an alkaline diet, highlighting the potential role of alkaline diet in countering cognitive decline associated with aging.

Metabolic-dysfunction associated steatotic liver disease-related diseases, cognition and dementia: A two-sample mendelian randomization study.

BACKGROUND: The results of current studies on metabolic-dysfunction associated steatotic liver disease (MASLD)-related diseases, cognition and dementia are inconsistent. This study aimed to elucidate the effects of MASLD-related diseases on cognition and dementia. METHODS: By using single-nucleotide polymorphisms (SNPs) associated with different traits of NAFLD (chronically elevated serum alanine aminotransferase levels [cALT], imaging-accessed and biopsy-proven NAFLD), metabolic dysfunction-associated steatohepatitis, and liver fibrosis and cirrhosis, we employed three methods of mendelian randomization (MR) analysis (inverse-variance weighted [IVW], weighted median, and MR-Egger) to determine the causal relationships between MASLD-related diseases and cognition and dementia. We used Cochran's Q test to examine the heterogeneity, and MR-PRESSO was used to identify outliers (NbDistribution = 10000). The horizontal pleiotropy was evaluated using the MR-Egger intercept test. A leave-one-out analysis was used to assess the impact of individual SNP on the overall MR results. We also repeated the MR analysis after excluding SNPs associated with confounding factors. RESULTS: The results of MR analysis suggested positive causal associations between MASLD confirmed by liver biopsy (p of IVW = 0.020, OR = 1.660, 95%CI = 1.082-2.546) and liver fibrosis and cirrhosis (p of IVW = 0.009, OR = 1.849, 95%CI = 1.169-2.922) with vascular dementia (VD). However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance and other types of dementia (any dementia, Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia). Sensitivity tests supported the robustness of the results. CONCLUSIONS: This two-sample MR analysis suggests that genetically predicted MASLD and liver fibrosis and cirrhosis may increase the VD risk. Nonetheless, the causal effects of NAFLD-related diseases on VD need more in-depth research.

Risk factors for cognitive impairment in middle-aged type 2 diabetic patients: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate risk factors for cognitive impairment (CI) and explore the relationship between obesity and cognition in hospitalised middle-aged patients with type 2 diabetes (T2DM). METHODS: Subjects were divided into normal cognitive function (NCF) (n=320) and CI (n=204) groups based on the results of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). The risk factors for CI were determined by logistic regression analysis and generalised linear modelling. The associations between obesity parameters (body mass index (BMI) and waist circumference (WC)) and cognitive ability were studied with the use of linear regression analysis, piecewise regression modelling and interaction analysis. The receiver operating characteristic curve analysis was used to examine the diagnostic value of influencing factors for cc RESULTS: The prevalence of CI was 38.9% in hospitalised middle-aged T2DM patients (median age, 58 years). Age, WC, hypoglycaemic episode within past 3 months and cerebrovascular disease (CVD) were identified as independent risk factors for CI, while the independent protective factors were education, diabetic dietary pattern, overweight and obesity. BMI was a protective factor for the MoCA score within a certain range, whereas WC was a risk factor for the MMSE and MoCA scores. The area under the curve for the combination of BMI and WC was 0.754 (p<0.001). CONCLUSION: Age, education, diabetic dietary pattern, WC, overweight, obesity, hypoglycaemic episode in 3 months and CVD may be potential influencing factors for the occurrence of CI in hospitalised middle-aged population with T2DM. The combination of BMI and WC may represent a good predictor for early screening of CI in this population. Nevertheless, more relevant prospective studies are still needed.

Relationships Between Body Composition and Cognitive Impairment in Hospitalised Middle-Aged Type 2 Diabetic Patients.

Objective: The aim of this study was to elucidate the relationship between specific body composition and the risk of Cognitive Impairment (CI) in middle-aged Type 2 Diabetes Mellitus (T2DM) patients. Methods: This cross-sectional study included 504 hospitalized patients with T2DM from the Department of Endocrinology and Metabolism of the Tianjin Union Medical Center. Subjects were grouped by sex, and cognitive status was assessed using the Montreal Cognitive Assessment (MoCA). The relationship between body composition and cognitive ability was investigated with the use of linear regression analysis. The association between body composition and CI risk was determined by logistic regression analysis. Results: The prevalence of CI was 39.3% in middle-aged T2DM patients. After adjusting for age, education, marriage status, carotid atherosclerosis, cerebrovascular disease and hemoglobin, multiple linear regression analysis showed that lean mass index (LMI), body mass index (BMI) and appendicular skeletal muscle index (SMI) were significant predictors for the MoCA scores in men (p < 0.05). In addition, BMI (OR 0.913, 95% CI 0.840-0.992) and LMI (OR 0.820, 95% CI 0.682-0.916) were independent protective factors for CI in males. After adjusted for age, education, marriage status, dietary control of diabetes and cerebrovascular disease, visceral obesity (VO, OR 1.950, 95% CI 1.033-3.684) and abdominal obesity (AO, OR 2.537, 95% CI 1.191-5.403) were risk factors for CI in female patients. Conclusion: The results suggest that there may be different mechanisms underlying the relationship of body compositions and cognitive performance between middle-aged male and female patients with T2DM. In addition, our finding of potential determinants of cognitive impairment may facilitate the development of intervention programs for middle-aged type 2 diabetic patients. Nevertheless, more large prospective studies looking at cognition and changes in body composition over time are needed in the future to further support their association.

Effect and Mechanism of Sodium Butyrate on Neuronal Recovery and Prognosis in Diabetic Stroke.

Ischemic stroke is a cerebrovascular lesion caused by local ischemia and hypoxia. Diabetes mellitus (DM) is a chronic inflammatory disease that disturbs immune homeostasis and predisposes patients to ischemic stroke. The mechanism by which DM exacerbates stroke remains unclear, although it may involve disturbances in immune homeostasis. Regulatory T cells (Tregs) play a regulatory role in many diseases, but the mechanism of Tregs in diabetes complicated by stroke remains unclear. Sodium butyrate is a short-chain fatty acid that increases Treg levels. This study examined the role of sodium butyrate in the prognosis of neurological function in diabetic stroke and the mechanism by which Tregs are amplified in the bilateral cerebral hemispheres. We evaluated the brain infarct volume, observed 48-h neuronal injury and 28-day behavioral changes, and calculated the 28-day survival rate in mice. We also measured Treg levels in peripheral blood and brain tissue, recorded changes in the blood‒brain barrier and water channel proteins and neurotrophic changes in mice, measured cytokine levels and peripheral B-cell distribution in bilateral hemispheres and peripheral blood, and examined the polarization of microglia and the distribution of peripheral T-cell subpopulations in bilateral hemispheres. Diabetes significantly exacerbated the poor prognosis and neurological deficits in mice with stroke, and sodium butyrate significantly improved infarct volume, prognosis, and neurological function and showed different mechanisms in brain tissue and peripheral blood. The potential regulatory mechanism in brain tissue involved modulating Tregs/TGF-ß/microglia to suppress neuroinflammation, while that in peripheral blood involved improving the systemic inflammatory response through Tregs/TGF-ß/T cells.

Comparison of lipid accumulation product and visceral adiposity index with traditional obesity indices in early-onset type 2 diabetes prediction: a cross-sectional study.

BACKGROUND: The purpose of the study was to compare the efficacy of two novel obesity indices, lipid accumulation product (LAP) and visceral adiposity index (VAI), with traditional obesity indices in predicting early-onset type 2 diabetes (T2DM). METHODS: In this cross-sectional study, a total of 744 participants, including 605 patients newly diagnosed with T2DM and 139 non-diabetic control subjects, were enrolled from a tertiary care hospital in Tianjin, China. Participants with T2DM were divided into two groups based on their age at diagnosis, namely early-onset T2DM (age less than 40 years, n = 154) and late-onset T2DM (age 40 years or older, n = 451). The predictive power of each obesity index was evaluated using receiver operating characteristic (ROC) curve analysis. Furthermore, binary logistic regression analysis was conducted to examine the independent relationship between LAP and VAI with early-onset T2DM risk. The relationship between novel obesity indices and the age of T2DM onset was also evaluated through correlation and multiple linear regression analysis. RESULTS: In males, LAP had the highest predictive power for early-onset T2DM with an area under the ROC curve (AUC) of 0.742 (95% CI 0.684-0.799, P < 0.001). In females, VAI had the highest AUC for early-onset T2DM with a value of 0.748 (95% CI 0.657-0.839, P < 0.001), which was superior to traditional indices. Patients in the 4th quartile of LAP and VAI had 2.257 (95% CI 1.116-4.563, P = 0.023) and 4.705 (95% CI 2.132-10.384, P < 0.001) times higher risk of T2DM before age 40, compared to those in the 1st quartile, respectively. A tenfold increase in LAP was associated with a decrease in T2DM onset age of 12.862 years in males (ß = -12.862, P < 0.001) and 6.507 years in females (ß = -6.507, P = 0.013). A similar decrease in T2DM onset age was observed for each tenfold increase in VAI in both male (ß = -15.222, P < 0.001) and female (ß = -12.511, P < 0.001) participants. CONCLUSIONS: In young Chinese individuals, LAP and VAI are recommended over traditional obesity indices for improved prediction of early-onset T2DM risk.

Low-normal serum unconjugated bilirubin levels are associated with late but not early carotid atherosclerotic lesions in T2DM subjects.

Aims: We aimed to examine the association of serum unconjugated bilirubin (UCB) within normal limits with carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional, real-world study was performed in 8,006 hospitalized T2DM patients including 4,153 men and 3,853 women with normal UCB. The subjects were stratified into quintiles based on serum UCB levels (<6.2, 6.2-7.9, 8.0-8.9, 9.0-10.9, and >10.9 µmol/l, respectively). Carotid atherosclerotic lesions detected by ultrasonography, including carotid intima-media thickness (CIMT), carotid plaque, and stenosis, were compared among the five groups. The associations of serum UCB levels and quintiles with carotid atherosclerotic lesions were also determined by multiple logistic regression. Results: The prevalence of carotid plaque (55.3%, 49.5%, 47.4%, 43.8%, and 37.5%, respectively; p < 0.001 for trend) and stenosis (15.2%, 12.2%, 9.1%, 7.7%, and 5.4%, respectively; p < 0.001 for trend) was progressively lower across the UCB quintiles even after adjusting for age, sex, and duration of diabetes. Results of a fully adjusted multiple logistic regression analysis revealed that serum UCB levels and quintiles were significantly associated with carotid plaque and stenosis. Compared with the subjects in the lowest UCB quintile, the risk of carotid plaque decreased by 25.5%, 28.7%, 33.5%, and 42.8%, and that of carotid stenosis by 24.6%, 37.4%, 44.9%, and 47.3%, respectively, in those from the second to highest UCB quintiles. High serum UCB within the normal range was a protective factor against carotid plaque [odds ratio (OR) 0.810, 95% confidence interval (CI) 0.747-0.878; p < 0.001] and stenosis [OR 0.722, 95% CI 0.647-0.805; p < 0.001]. However, no significant association was observed between serum UCB and CIMT in T2DM patients. Furthermore, C-reactive protein (CRP) levels were significantly higher in the subjects with carotid atherosclerosis than in those without carotid atherosclerosis and clearly decreased across the UCB quintiles. Conclusions: Serum UCB within normal limits is inversely associated with late carotid atherosclerotic lesions including carotid plaque and stenosis but not CIMT, an early carotid atherosclerotic lesion in T2DM patients. High-normal UCB may be protective against carotid atherosclerosis by its anti-inflammation effect, which was indicated by significantly decreased CRP levels from the lowest to highest UCB quintiles.

Cytotoxic effects of extracts and isolated compounds from Ifloga spicata (forssk.) sch. bip against HepG-2 cancer cell line: Supported by ADMET analysis and molecular docking.

The purpose of this study was to determine the anticancer potential of Ifloga spicata (I. spicata) against HepG-2 cell line. To assess I. spicata cytoxicity, brine shrimp lethality and MTT assays were performed. In the brine shrimp bioassay, the ethyl acetate fraction had a significant impact with an IC50 of 10 µg/ml. The ethyl acetate and chloroform fractions inhibited HepG-2 cell line effectively (IC50 values 5.54 and 6.52 µg/ml, respectively). The isolated compound, heptadecyl benzoate inhibited growth significantly (IC50, 8.92 µg/ml) while methyl dihydroxybenzoate had modest activity (25.66 µg/ml) against the cell line. Both compounds displayed acceptable pharmacokinetic parameters in the ADME study. In the docking study, the methyl dihydroxybenzoate was involved in two hydrogen bonds with two different residues Thr830 and Asp831. The heptadecyl benzoate carbonyl oxygen exhibited a single hydrogen bond with Lys692. Both showed good interactions with the active site of the (EGFR) tyrosine kinase. Our findings suggest that I. spicata might be a viable source of anticancer natural agents. This discovery raises the prospect of the future development of a new medication for the treatment of liver cancer.

Systemic immune inflammation index and system inflammation response index are potential biomarkers of atrial fibrillation among the patients presenting with ischemic stroke.

BACKGROUND: Chronic inflammatory disorders in atrial fibrillation (AF) contribute to the onset of ischemic stroke. Systemic immune inflammation index (SIII) and system inflammation response index (SIRI) are the two novel and convenient measurements that are positively associated with body inflammation. However, little is known regarding the association between SIII/SIRI with the presence of AF among the patients with ischemic stroke. METHODS: A total of 526 ischemic stroke patients (173 with AF and 353 without AF) were consecutively enrolled in our study from January 2017 to June 2019. SIII and SIRI were measured in both groups. Logistic regression analysis was used to analyse the potential association between SIII/SIRI and the presence of AF. Finally, the correlation between hospitalization expenses, changes in the National Institutes of Health Stroke Scale (NIHSS) scores and SIII/SIRI values were measured. RESULTS: In patients with ischemic stroke, SIII and SIRI values were significantly higher in AF patients than in non-AF patients (all p < 0.001). Moreover, with increasing quartiles of SIII and SIRI in all patients, the proportion of patients with AF was higher than that of non-AF patients gradually. Logistic regression analyses demonstrated that log-transformed SIII and log-transformed SIRI were independently associated with the presence of AF in patients with ischemic stroke (log-transformed SIII: odds ratio [OR]: 1.047, 95% confidence interval CI = 0.322-1.105, p = 0.047; log-transformed SIRI: OR: 6.197, 95% CI = 2.196-17.484, p = 0.001). Finally, a positive correlation between hospitalization expenses, changes in the NIHSS scores and SIII/SIRI were found, which were more significant in patients with AF (all p < 0.05). CONCLUSIONS: Our study suggests SIII and SIRI are convenient and effective measurements for predicting the presence of AF in patients with ischemic stroke. Moreover, they were correlated with increased financial burden and poor short-term prognosis in AF patients presenting with ischemic stroke.

[Study on Impedance of Implantable Cardiac Pacemaker in Unipolar/Bipolar Pacing Mode by in Vitro Experiment].

The unipolar/bipolar pacing mode of pacemaker is related to its circuit impedance, which affects the battery life. In this study, the in vitro experiment scheme of pacemaker circuit impedance test was constructed. The human blood environment was simulated by NaCl solution, and the experimental environment temperature was controlled by water bath. The results of in vitro experiments showed that under the experimental conditions similar to clinical human parameters, the difference between the circuit impedance of bipolar mode and unipolar mode is 120~200 Ω. The results of the in vitro experiment confirmed that the circuit impedance of bipolar circuit was larger than that of unipolar mode, which was found in clinical practice. The results of this study have reference value to the optimization of pacing mode and the reduction of pacemaker power consumption.

Association of Mild Thyroid Dysfunction and Adverse Prognosis Among Chinese Patients With Acute ST Segment Elevation Myocardial Infarction.

Aims: Thyroid hormones widely affect the cardiovascular system, but the effects of mild thyroid dysfunction on the clinical prognosis of patients with acute ST segment elevation myocardial infarction (STEMI) remains unclear. Our aims were to analyze the relations between mild thyroid dysfunction at admission and clinical outcomes in Chinese patients with STEMI. Methods: A total of 1,176 STEMI patients with the available data of thyroid function and follow-up were analyzed, including 348 patients with mild thyroid dysfunction [subclinical hypothyroidism (n=81), hyperthyroidism (SHyper) (n=51), and low triiodothyronine syndrome (LT3S) (n=216)] and 828 patients with euthyroid function. During a median 4.4-year follow-up, in-hospital mortality, cardiac and all-cause mortalities were subsequently compared among the four groups. Results: Compared with the euthyroid group, STEMI patients in the SHyper and LT3S groups faced obviously increased risks of in-hospital death [odds ratio (OR): 5.007, 95% confidence interval (CI): 1.246-20.124, p = 0.023 and OR: 2.491, 95% CI: 1.054-5.887, p = 0.037, respectively) even after adjustment for various confounding factors. During a median 4.4-year follow-up, STEMI patients with LT3S at baseline had higher cardiovascular mortality [hazard ratio (HR): 1.880, 95% CI: 1.178-2.998, p = 0.008] and all-cause mortality HR: 1.647, 95% CI: 1.072-2.531, p = 0.023] than those with euthyroid at baseline, whereas no significantly increased mortality was found for STEMI patients with SCH and SHyper at baseline. Conclusions: STEMI patients with SHyper at admission had increased risk of in-hospital mortality, and STEMI patients with LT3S at baseline had worse prognosis and higher incidences of in-hospital mortality and cardiovascular and all-cause deaths compared with euthyroid patients.

Identification of novel and potential PPARγ stimulators as repurposed drugs for MCAO associated brain degeneration.

Peroxisome proliferator-activated receptor-gamma (PPARγ) has been shown to have therapeutic promise in the treatment of ischemic stroke and is supported by several studies. To identify possible PPARγ activators, the current study used an in silico technique in conjunction with molecular simulations and in vivo validation. FDA-approved drugs were evaluated using molecular docking to determine their affinity for PPARγ. The findings of molecular simulations support the repurposing of rabeprazole and ethambutol for the treatment of ischemic stroke. Adult Sprague Dawley rats were subjected to transient middle cerebral artery occlusion (t-MCAO). Five groups were made as a sham-operated, t-MCAO group, rabeprazole +t-MCAO, ethambutol +t-MCAO, and pioglitazone +t-MCAO. The neuroprotective effects of these drugs were evaluated using the neurological deficit score and the infarct area. The inflammatory mediators and signaling transduction proteins were quantified using Western blotting, ELISA, and immunohistochemistry. The repurposed drugs mitigated cerebral ischemic injury by PPARγ mediated downregulation of nods like receptor protein 3 inflammasomes (NLRP3), tumor necrosis factor-alpha (TNF-α), cyclooxygenase 2 (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-kB), and c-Jun N-terminal kinase (p-JNK). Our data demonstrated that rabeprazole and ethambutol have neuroprotective potential via modulating the cytoprotective stress response, increasing cellular survival, and balancing homeostatic processes, and so may be suitable for future research in stroke therapy.

Serum free triiodothyronine is inversely associated with diabetic peripheral neuropathy but not with carotid atherosclerotic lesions in euthyroid patients with type 2 diabetes.

BACKGROUND: The associations between serum free triiodothyronine (FT3) and diabetic peripheral neuropatprohy (DPN)/carotid atherosclerotic lesions in euthyroid patients with type 2 diabetes are still unclear. The purpose of our study was to explore the relations of FT3 to DPN and carotid atherosclerotic lesions in Chinese type 2 diabetes inpatients with euthyroid function. METHODS: 2477 euthyroid inpatients with type 2 diabetes were recruited and they were stratified into quartiles by FT3 levels in this cross-sectional study. Peripheral neuropathy was assessed by neurological symptoms and signs as well as nerve conduction velocity tests. Carotid atherosclerotic lesions, including carotid intima-media thickness, plaque and stenosis, were evaluated by Doppler ultrasound. RESULTS: The prevalence of DPN in type 2 diabetic patients exhibited the significant decrease across the FT3 quartiles (23.5%, 20.9%, 18.8%, and 11.2%, respectively, p < 0.001). Multiple logistical regression analysis also revealed that FT3 quartiles were significantly and inversely associated with DPN. Compared with the subjects in the highest FT3 quartile, the adjusted odds ratios (95% confidence interval) of DPN from the first to third FT3 quartile were successively 2.338 (1.407-3.884), 1.903 (1.134-3.194) and 1.598 (0.960-1.125). The patients with DPN had significantly higher prevalence of carotid atherosclerotic lesions compared with non-DPN patients. However, no statistical association was observed between FT3 quartiles and carotid atherosclerotic lesions after adjusting for confounder factors. CONCLUSIONS: Lower FT3 within the normal range was independently associated with DPN, but not with carotid atherosclerotic lesions in Chinese euthyroid inpatients with type 2 diabetes.

Amino Acid Conjugates of Aminothiazole and Aminopyridine as Potential Anticancer Agents: Synthesis, Molecular Docking and in vitro Evaluation.

PURPOSE: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate this therapeutic failure. The current study demonstrated the synthesis of 2-aminothiazole [S3(a-d) and S5(a-d)] and 2-aminopyridine [S4(a-d) and S6(a-d)] derivatives that can target multiple cellular networks implicated in cancer development. METHODS: Biological assays were performed to investigate the antioxidant and anticancer potential of synthesized compounds. Redox imbalance and oxidative stress are hallmarks of cancer, therefore, synthesized compounds were preliminarily screened for their antioxidant activity using DPPH assay, and further five derivatives S3b, S3c, S4c, S5b, and S6c, with significant antioxidant potential, were selected for investigation of in vitro anticancer potential. The cytotoxic activities were evaluated against the parent (A2780) and cisplatin-resistant (A2780CISR) ovarian cancer cell lines. Further, Molecular docking studies of active compounds were performed to determine binding affinities. RESULTS: Results revealed that S3c, S5b, and S6c displayed promising inhibition in cisplatin-resistant cell lines in comparison to parent cells in terms of both resistance factor (RF) and IC50 values. Moreover, S3c proved to be most active compound in both parent and resistant cell lines with IC50 values 15.57 µM and 11.52 µM respectively. Our docking studies demonstrated that compounds S3c, S5b, and S6c exhibited significant binding affinity with multiple protein targets of the signaling cascade. CONCLUSION: Anticancer activities of compounds S3c, S5b, and S6c in cisplatin-resistant cell lines suggested that these ligands may contribute as lead compounds for the development of new anticancer drugs.

Maternal Pre-Pregnancy Obesity Combined With Abnormal Glucose Metabolism Further Increases Adverse Pregnancy Outcomes in Chinese Pregnant Women.

Aims: Our aim was to evaluate the separate and combined effects of maternal pre-pregnancy obesity and gestational abnormal glucose metabolism (GAGM) on adverse perinatal outcomes. Methods: A total of 2,796 Chinese pregnant women with singleton delivery were studied, including 257 women with pre-pregnancy obesity alone, 604 with GAGM alone, 190 with both two conditions, and 1,745 with neither pre-pregnancy obesity nor GAGM as control group. The prevalence and risks of adverse pregnancy outcomes were compared among the four groups. Results: Compared with the normal group, pregnant women with maternal pre-pregnancy obesity alone, GAGM alone, and both two conditions faced significantly increased risks of pregnancy-induced hypertension (PIH) (odds ratio (OR) 4.045, [95% confidence interval (CI) 2.286-7.156]; 1.993 [1.171-3.393]; 8.495 [4.982-14.485]), preeclampsia (2.649 [1.224-5.735]; 2.129 [1.128-4.017]; 4.643 [2.217-9.727]), cesarean delivery (1.589 [1.212-2.083]; 1.328 [1.095-1.611]; 2.627 [1.908-3.617]), preterm delivery (1.899 [1.205-2.993]; 1.358 [0.937-1.968]; 2.301 [1.423-3.720]), macrosomia (2.449 [1.517-3.954]; 1.966 [1.356-2.851]; 4.576 [2.895-7.233]), and total adverse maternal outcomes (1.762 [1.331-2.332]; 1.365 [1.122-1.659]; 3.228 [2.272-4.587]) and neonatal outcomes (1.951 [1.361-2.798]; 1.547 [1.170-2.046]; 3.557 [2.471-5.122]). Most importantly, there were no obvious risk differences in adverse pregnancy outcomes between maternal pre-pregnancy obesity and GAGM group except PIH, but pregnant women with both obesity and GAGM exhibited dramatically higher risks of adverse pregnancy outcomes than those with each condition alone. Conclusions: Maternal pre-pregnancy obesity and GAGM were independently associated with increased risks of adverse pregnancy outcomes. The combination of pre-pregnancy obesity and GAGM further worsens adverse pregnancy outcomes compared with each condition alone.

Impact of B-mode-ultrasound-guided transhepatic and transperitoneal cholecystostomy tube placement on laparoscopic cholecystectomy.

BACKGROUND: B-mode-ultrasound-guided percutaneous cholecystostomy (PC) may be performed by a transhepatic or transperitoneal approach, called percutaneous transhepatic gallbladder drainage (PHGD) and percutaneous transperitoneal gallbladder drainage (PPGD), respectively. We compared the impact of PC related to the route of catheter placement on subsequent laparoscopic cholecystectomy (LC). AIM: To compare the impact of PC related to the route of catheter placement on subsequent LC. METHODS: We retrospectively studied 103 patients with acute calculous cholecystitis who underwent scheduled LC after PC between January 2010 and January 2019. Group I included 58 patients who underwent scheduled LC after PHGD. Group II included 45 patients who underwent scheduled LC after PPGD. Clinical outcomes were analyzed according to each group. RESULTS: Baseline demographic characteristics did not differ significantly between both groups (P > 0.05). Both PHGD and PPGD were able to quickly resolve cholecystitis sepsis. Group I showed significantly higher efficacy than group II in terms of lower pain score during puncture (3.1 vs 4.5; P = 0.001) and at 12 h follow-up (1.5 vs 2.2; P = 0.001), lower rate of fever within 24 h after PC (13.8% vs 42.2%; P = 0.001), shorted operation duration (118.3 vs 139.6 min; P = 0.001), lower amount of intraoperative bleeding (72.1 vs 109.4 mL; P = 0.001) and shorter length of hospital stay (14.3 d vs 18.0 d; P = 0.001). However, group II had significantly lower rate of local bleeding at the PC site (2.2% vs 20.7%; P = 0.005) and lower rate of severe adhesion (33.5% vs 55.2%; P = 0.048). No significant differences were noted between both groups regarding the conversion rate to laparotomy, rate of subtotal cholecystectomy, complications and pathology. CONCLUSION: B-mode-ultrasound-guided PHGD is superior to PPGD followed by LC for treatment of acute calculous cholecystitis, with shorter operating time, minimal amount of intraoperative bleeding and short length of hospital stay.

A new genus and species of gall midge (Diptera: Cecidomyiidae) inducing leaf galls on Peking lilac, Syringa reticulata subsp. pekinensis (Oleaceae), in China.

Larvae of a previously unknown species of gall midge were found causing large numbers of pustulate leaf galls on Peking lilac, Syringa reticulata subsp. pekinensis (Oleaceae), in parklands and street greenery in Beijing, China. Heavily galled leaves become senescent and fall off prematurely. The gall midge is named Pekinomyia syringae Jiao Kolesik, its morphology is described and the COI mitochondrial gene and 12S ribosomal gene segments are sequenced. A new genus, Pekinomyia Jiao Kolesik (Cecidomyiinae: Lasiopteridi), is erected for the new species. The new genus differs from other Lasiopteridi in the strongly sclerotized aedeagus and the lack of mesobasal lobes in the male terminalia and is not assigned to any known tribe.

Impaired Left Atrial Performance Resulting From Age-Related Arial Fibrillation Is Associated With Increased Fibrosis Burden: Insights From a Clinical Study Combining With an in vivo Experiment.

Background: Atrial fibrillation (AF) is increasingly considered an age-related degenerative disease, whose process is associated with the development of impaired left atrial (LA) performance. However, the subtle dynamic changes of LA performance in AF during aging have yet to be fully elucidated. Atrial fibrosis is a key substrate for the development of AF, but the progression of fibrosis during aging and its relationship with LA dysfunction need to be further explored. Methods: A total of 132 control individuals and 117 persistent AF patients were prospectively studied. Subjects were further stratified into three age groups (age group 1: younger than 65 years, age group 2: between 65 and 79 years old, and age group 3: older than 80 years). The two-dimensional speckle tracking imaging was carried out for analyzing the alterations in LA function underlying LA remodeling, whereas electroanatomic mapping was performed to investigate LA fibrosis burden. In animal study, aged mice and young mice served as research subjects. Echocardiography and histological staining were used to assess LA performance and fibrosis burden, respectively. Results: Echocardiography showed progressive increases in LA dimension and LA stiffness index, and progressive decreases in LA global longitudinal strain and LA strain rates with advancing age in both AF and control cohorts, which was more prominent in AF cohort. Electroanatomic mapping showed progressive decrease in mean LA voltage and progressive increases in LA surface area, low-voltage area %, and LA volume with advancing age, whereas more significant alterations were observed in AF patients. Moreover, left atrial global longitudinal strain was positively correlated with mean LA voltage, whereas LA stiffness index was negatively related to mean LA voltage. In animal experiment, increased LA size and pulmonary artery dimension as well as longer P-wave duration and more prominent LA fibrosis were found in aged mice. Conclusions: This study provides new evidence of subtle changes in structure and performance of left atrium and their association with atrial fibrosis in both AF and non-AF subjects during physiological aging. In addition, our study also provides normal values for LA structure and performance in both AF and non-AF conditions during aging. These measurements may provide an early marker for onset of AF and LA adverse remodeling.

Carveol a Naturally-Derived Potent and Emerging Nrf2 Activator Protects Against Acetaminophen-Induced Hepatotoxicity.

Acetaminophen (N-acetyl p-aminophenol or APAP) is used worldwide for its antipyretic and anti-inflammatory potential. However, APAP overdose sometimes causes severe liver damage. In this study, we elucidated the protective effects of carveol in liver injury, using molecular and in silico approaches. Male BALB/c mice were divided into two experimental cohorts, to identify the best dose and to further assess the role of carveol in the nuclear factor E2-related factor; nuclear factor erythroid 2; p45-related factor 2 (Nrf2) pathway. The results demonstrated that carveol significantly modulated the detrimental effects of APAP by boosting endogenous antioxidant mechanisms, such as nuclear translocation of Nrf2 gene, a master regulator of the downstream antioxidant machinery. Furthermore, an inhibitor of Nrf2, called all-trans retinoic acid (ATRA), was used, which exaggerated APAP toxicity, in addition to abrogating the protective effects of carveol; this effect was accompanied by overexpression of inflammatory mediators and liver = 2ltoxicity biomarkers. To further support our notion, we performed virtual docking of carveol with Nrf2-keap1 target, and the resultant drug-protein interactions validated the in vivo findings. Together, our findings suggest that carveol could activate the endogenous master antioxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating the APAP-induced inflammation and oxidative stress.