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Yangfan Du,1 Na Li,1 Xin Jiao,2 Kai Li,1 Shunchao Yan1 1Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, People’s Republic of China; 2Department of Respiratory Medicine, Shenyang Chest Hospital, Shenyang 110044, People’s Republic of China Purpose: The predictive ability of plasma ESR1 mutations for outcomes among patients with advanced breast cancer undergoing endocrine therapy (ET) remains disputable. We performed a comprehensive meta-analysis of published studies to clarify the impact of plasma ESR1 mutations on clinical outcomes for patients after subsequent ET. Materials and methods: An electronic search was performed to identify eligible studies. Studies analyzing progression-free survival (PFS) and/or overall survival (OS) according to plasma ESR1 mutation status after subsequent ET were included. HRs were calculated using a fixed- or random-effects model according to heterogeneity. Pooled HRs and 95% CIs were used to estimate the effects. Results: Six studies including 705 patients with advanced breast cancer met the inclusion criteria. The impact of plasma ESR1 mutations on PFS and OS after subsequent ET was reported in six studies (seven groups) and two studies, respectively. Meta-analysis results showed that the pooled HR for ESR1 mutations was 1.70 (95% CI, 1.05–2.74; P=0.03) for OS, which was statistically significant for predicting poor survival, and 1.56 (95% CI, 1.13–2.14; P=0.006) for PFS; however, Begg’s and Egger’s test results identified the presence of bias. The trim-and-fill method was used, and after incorporation of the imputed studies, the HR was 1.16 (95% CI, 0.88–1.53, P=0.30) for PFS, which indicates that plasma ESR1 mutation had no effect on PFS after subsequent ET. Subgroup analysis suggested that plasma ESR1 mutations were correlated with shorter PFS (HR, 1.98; 95% CI, 1.12–3.51; P=0.02) in patients subsequently treated with aromatase inhibitors (AIs), whereas no association with PFS was observed for patients subsequently treated with non-AI ET (HR, 1.08; 95% CI, 0.85–1.38; P=0.54) or fulvestrant (HR, 1.03; 95% CI, 0.79–1.34; P=0.83). Conclusion: The current meta-analysis demonstrates that plasma ESR1 mutation status is not a predictor of ET efficacy for all drugs without distinction in patients with hormone-receptor-positive advanced breast cancer. ESR1 mutation predicted a poor response to AIs, whereas it was not predictive of non-AI ET efficacy, especially for fulvestrant. Keywords: ESR1 mutation, breast cancer, endocrine therapy, efficacy predictor

Ching-Han Lin,1,* Shang-Yu Lee,2,* Chun-Cheng Zhang,3 Ye-Fong Du,1 Hao-Chang Hung,1 Hung-Tsung Wu,4 Horng-Yih Ou1 1Department of Internal Medicine, Division of Endocrinology and Metabolism, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 2Department of Internal Medicine, Division of Endocrinology and Metabolism, Chi-Mei Medical Center, 3Department of Internal Medicine, Division of Holistic Care, Chi-Mei Medical Center, 4Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, Taiwan *These authors contributed equally to this work Abstract: Fenretinide is a novel anticancer agent reported to exhibit anti-invasive and antimetastatic activities. It has also been shown to improve obesity and diabetes, although the effects of fenretinide on hypertension are still unknown, and the detailed mechanisms remain unclear. In this study, we have shown that treatment with lipopolysaccharide (LPS) decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ) in RAW264.7 macrophages, and pretreatment with fenretinide reversed the effect of LPS on PPARγ expression. In addition, LPS-induced pro-inflammatory cytokine production, including tumor necrosis factor-α, interleukin 6, and monocyte chemoattractant protein 1 were dose-dependently reversed by fenretinide, and the effects of fenretinide on LPS-induced pro-inflammatory cytokine production were blocked by treatment with PPARγ antagonist. Moreover, fenretinide decreased LPS-induced inducible nitric oxide synthase expression and nitrogen oxide production. These effects were blocked by the pretreatment with PPARγ antagonist in a dose-dependent manner, indicating fenretinide activated PPARγ to exert anti-inflammation activity. In view of the role of inflammation in hypertension and the anti-inflammatory action of fenretinide, we found that administration of fenretinide in spontaneously hypertensive rats significantly decreased blood pressure. Taken together, these results indicate that fenretinide might be a potent antihypertensive agent that works by suppressing inflammation via activating PPARγ. Keywords: fenretinide, hypertension, inflammation, macrophage, peroxisome proliferator-activated receptor γ

Xiao-Xia Zhang,1,* Yue-Feng Du,2,* Ya-Jing Zhai,1 Fan Gao,3 Yu-Juan Yang,4 Xian-Cang Ma,3 Jun Lu,3 Jie Zheng31Department of Pharmacy, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Urology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Clinical Research Center, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4The Third Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workAbstract: Acute lymphoblastic leukemia (ALL) has been studied intensively for decades, but the details of its etiology and underlying mechanisms have yet to be fully elucidated. It is now generally acknowledged that genetic factors contribute greatly to the development of this disease. The gene encoding CCAAT/enhancer-binding protein ε (CEBPE) is involved in the development of leukemia, and in particular the rs2239633 single nucleotide polymorphism (SNP) of CEBPE. The association between rs2239633 and risk of ALL has been well studied, but remains unclear. Therefore, a meta-analysis was performed in this study to establish a more precise estimation of that relationship. A comprehensive literature search of the PubMed electronic database was conducted, and relevant studies published up to February 20, 2015 were selected for analysis. The references of the retrieved articles were also screened. The extracted data were analyzed statistically, and pooled odds ratios with 95% confidence intervals were calculated using Review Manager (version 5.2) to estimate the association strength. Finally, eleven studies were included in the meta-analysis. The pooled analyses revealed that rs2239633 was associated with an increased risk of childhood ALL in Caucasians under any contrast models (P

Ye-Fong Du,1 Horng-Yih Ou,1 Elizabeth A Beverly,2 Ching-Ju Chiu3 1Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 2Department of Social Medicine, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA; 3Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan Abstract: The prevalence of type 2 diabetes mellitus (T2DM) is increasing in the elderly. Because of the unique characteristics of elderly people with T2DM, therapeutic strategy and focus should be tailored to suit this population. This article reviews the guidelines and studies related to older people with T2DM worldwide. A few important themes are generalized: 1) the functional and cognitive status is critical for older people with T2DM considering their life expectancy compared to younger counterparts; 2) both severe hypoglycemia and persistent hyperglycemia are deleterious to older adults with T2DM, and both conditions should be avoided when determining therapeutic goals; 3) recently developed guidelines emphasize the avoidance of hypoglycemic episodes in older people, even in the absence of symptoms. In addition, we raise the concern of glycemic variability, and discuss the rationale for the selection of current options in managing this patient population. Keywords: glycemic target, glycemic variability, blood glucose, frailty

Background and Purpose: Delayed cerebral ischemia is hard to diagnose early due to gradual, symptomless development. This study aimed to develop an automated model for predicting delayed cerebral ischemia following aneurysmal SAH on NCCT., Materials and Methods: This retrospective study included 400 patients with aneurysmal SAH (156 with delayed cerebral ischemia) who underwent NCCT. The study used ATT-Deeplabv3+ for automatically segmenting hemorrhagic regions using semisupervised learning. Principal component analysis was used for reducing the dimensionality of deep learning features extracted from the average pooling layer of ATT-DeepLabv3+. The classification model integrated clinical data, radiomics, and deep learning features to predict delayed cerebral ischemia. Feature selection involved Pearson correlation coefficients, least absolute shrinkage, and selection operator regression. We developed models based on clinical features, clinical-radiomics, and a combination of clinical, radiomics, and deep learning. The study selected logistic regression, Naive Bayes, Adaptive Boosting (AdaBoost), and multilayer perceptron as classifiers. The performance of segmentation and classification models was evaluated on their testing sets using the Dice similarity coefficient for segmentation, and the area under the receiver operating characteristic curve (AUC) and calibration curves for classification., Results: The segmentation process achieved a Dice similarity coefficient of 0.91 and the average time of 0.037 s/image. Seventeen features were selected to calculate the radiomics score. The clinical-radiomics-deep learning model with multilayer perceptron achieved the highest AUC of 0.84 (95% CI, 0.72-0.97), which outperformed the clinical-radiomics model ( P  = .002) and the clinical features model ( P  = .001) with multilayer perceptron. The performance of clinical-radiomics-deep learning model using AdaBoost was significantly superior to its clinical-radiomics model ( P  = .027). The performance of the clinical-radiomics-deep learning model and the clinical-radiomics model with logistic regression notably exceeded that of the model based solely on clinical features ( P  = .028; P  = .046). The AUC of the clinical-radiomics-deep learning model with multilayer perceptron ( P  < .001) and the clinical-radiomics model with logistic regression ( P  = .046) were significantly higher than the clinical model with logistic regression. Of all models, the clinical-radiomics-deep learning model with multilayer perceptron showed best calibration., Conclusions: The proposed 2-stage end-to-end model not only achieves rapid and accurate segmentation but also demonstrates superior diagnostic performance with high AUC values and good calibration in the clinical-radiomics-deep learning model, suggesting its potential to enhance delayed cerebral ischemia detection and treatment strategies., (© 2024 by American Journal of Neuroradiology.)

To investigate the value of prognostic nutrition index (PNI) and systemic immunoinflammatory index (SII) for predicting pathological responses of patients with advanced gastric cancer (GC) after neo-adjuvant chemotherapy (NACT). The clinicopathological data of 326 patients with advanced GC who received NACT in Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City) from January 2017 to December 2021 were retrospectively collected. The SII and PNI of patients were calculated. The receiver operating characteristics (ROC) curve was leveraged for getting the optimal cutoff values of SII and PNI. The pathological response of patients after NACT, as obtained from their postoperative pathological examinations, was evaluated based on the tumor regression grade (TRG) criteria. Multivariate regression analysis was employed for identifying factors that led to various pathological responses after NACT in advanced GC patients. The log-rank test was utilized for between-group comparison of patients' survival curves. The SII and PNI were 507.45 and 48.48 respectively, and their levels were divided into high and low groups. Pathological response (TRG 0-1) was observed in 66 cases (20.25%), while non-pathological response (TRG 2-3) was observed in 260 cases (79.75%). The results of multivariate logistic regression analysis showed that tumor diameter < 5 cm, ypT T0-T2, ypN N0, chemotherapy regimen XELOX (capecitabine combined with oxaliplatin), SII < 507.45 (P=0.002), PNI > 48.48 were all independent factors affecting the pathological responses of advanced GC patients after NACT (all P < 0.05). With SII and PNI being included, the AUC was 0.821 (95% CI: 0.765-0.876), and the specificity was 87.90% and the sensitivity was 64.20%. The Kaplan-Meier survival curve analysis showed that NACT patients with tumor diameter < 5 cm, ypT T0-T2, ypN N0, XELOX chemotherapy regimen, SII < 507.45 and SII ≥ 507.45 had a higher survival rate. (P < 0.001). Before treatment, tumor diameter < 5 cm, ypT T0-T2, ypN N0, chemotherapy regimen XELOX, SII < 507.45, PNI > 48.48 were all independent factors affecting the pathological response of advanced GC patients after NACT. Moreover, the inclusion of SII and PNI increased the accuracy of predicting the pathological response of patients after NACT., Competing Interests: None., (AJCR Copyright © 2024.)

Background: Salt-sensitive hypertension is often more prone to induce damage to target organs such as the heart and kidneys. Abundant recent studies have demonstrated a close association between ferroptosis and cardiovascular diseases.Therefore, we hypothesize that ferroptosis may be closely associated with organ damage in salt-sensitive hypertension. This study aimed to investigate whether ferroptosis is involved in the occurrence and development of myocardial fibrosis and renal fibrosis in salt-sensitive hypertensive rats., Methods: Ten 7-week-old male Dahl salt-sensitive (Dahl-SS) rats were adaptively fed for 1 week, then randomly divided into two groups and fed either a normal diet (0.3% NaCl, NDS group) or a high-salt diet (8% NaCl, HDS group) for 8 weeks. Blood pressure of the rats was observed, and analysis of the hearts and kidneys of Dahl-SS rats was conducted via HE-staining, Masson-staining, Prussian-blue-staining, TEM, tissue iron content detection, MDA content detection, immunofluorescence, and Western blot., Results: Compared to the NDS group, rats in the HDS group increases in systolic blood pressure(SBP) and diastolic blood pressure(DBP)(P<0.05);collagen fiber accumulation was observed in the heart and kidney tissues (P<0.01), accompanied by alterations in mitochondrial ultrastructure,reduced mitochondrial volume, and increased density of the mitochondrial double membrane. Additionally,there were significant increases in both iron content and MDA levels(P<0.05). Immunofluorescence and Western blot results both indicated significant downregulation (P<0.05) of xCT and GPX4 proteins associated with ferroptosis in the HDS group., Conclusion: Ferroptosis is involved in the damage and fibrosis of the heart and kidney tissues in salt-sensitive hypertensive rats., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To analyze the nutritional status of progeria, and to provide reference for scientific nutritional management of progeria. Methods: This cross-sectional study included 15 children with progeria who were treated at Children's Hospital, Zhejiang University School of Medicine, between April 2022 and May 2023. Data of medical history, physical examination, laboratory tests, dietary survey and body composition were collected and analyzed. Results: Among 15 patients there were 7 males and 8 females, aged 7.8 (2.3, 10.8) years. Twelve of the 15 patients exhibited signs of malnutrition. A 24-hour dietary survey was carried out in 14 of them. The daily energy intake of 11 cases was below recommended levels. Carbohydrate intake was insufficient in 10 cases, protein intake was insufficient in 7 cases, and fat intake was insufficient in 12 cases. Deficiencies in calcium, magnesium, iron and zinc were noted in 13, 13, 9 and 10 cases, respectively. Body composition was determined by dual-energy X-ray absorptiometry in 8 cases, and the bone mineral density was below average in 5 of them. Conclusions: Malnutrition, characterized by reduced energy intake, micronutrient deficiencies, and alteration in body composition, is prevalent in children with progeria. Regular routine nutritional assessment and proper interventions may benefit their long-term health status.

Background: Natural bioactive molecules are important sources for the development of new drugs. However, most of them were limited in clinical applications due to their low aqueous solubility and bioavailability. Oridonin (ORI) is a powerful anticancer compound with above characteristics., Objective: This study aimed to find an effective method to improve the bioavailability of poorly soluble natural compounds, and explore the action mechanisms of them to promote their application., Results: In this study, ORI-nicotinamide (NCT) cocrystal was successfully prepared for the first time to overcome the defects of ORI. The solubility and oral bioavailability of cocrystal (COC) increased 1.34 and 1.18 times compared with ORI. Moreover, MTT assay was applied to compare the cytotoxicity of positive control drug sorafenib with ORI and COC. The IC 50 values of sorafenib, ORI and COC on HepG2 cells were 7.61, 8.79 and 7.36 nmol·mL -1 , which indicated that the cytotoxicity of ORI could be enhanced by cocrystal preparation. The cellular metabolomics was innovatively introduced to gain insight into the difference of cytotoxicity mechanism between ORI and COC. The results showed that there were 78 metabolites with significant differences in content between the two groups, while these differential metabolites were related to 11 metabolic pathways. Among these, glycerophospholipid metabolism and cysteine and methionine metabolism were the significant differential pathways, and the downregulation of PC(14:0/16:1(9z)) and upregulation of homocysteine were the likely main reasons for higher cytotoxicity of COC., Conclusions: This study has presented novel approaches for enhancing the bioavailability and drug efficacy of natural compounds, while also offering fresh insights into the underlying action mechanisms of pharmaceutical cocrystals., Competing Interests: Declaration of Competing Interest This manuscript has not been published or presented elsewhere in part or in entirety, and is not under consideration by another journal. There are no conflicts of interest to declare., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: Both diabetic and hypertensive nephropathy eventually progress to glomerulosclerosis. Previous studies revealed a potential role of endothelial-to-mesenchymal transition (EndMT) in the pathophysiology of glomerulosclerosis in diabetic rats. Therefore, we hypothesized that EndMT was also involved in the development of glomerulosclerosis in salt-sensitive hypertension. We aimed to explore the effects of high-salt diet on endothelial-to-mesenchymal transition (EndMT) in glomerulosclerosis in Dahl salt-sensitive (Dahl-SS) rats., Methods: Eight-week-old male rats were fed high-salt (8%NaCl; DSH group) or normal salt (0.3%NaCl; DSN group) for eight weeks, with systolic blood pressure (SBP), serum creatinine, urea, 24-hour urinary protein/sodium, renal interlobar artery blood flow, and pathological examination measured. We also examined endothelial-(CD31) and fibrosis-related protein(α-SMA) expressions in glomeruli., Results: High-salt diet increased SBP (DSH vs. DSN, 205.2 ± 8.9 vs. 135.4 ± 7.9 mm Hg, P < 0.01), 24-hour urinary protein (132.55 ± 11.75 vs. 23.52 ± 5.94 mg/day, P < 0.05), urine sodium excretions (14.09 ± 1.49 vs. 0.47 ± 0.06 mmol/day, P < 0.05), and renal interlobar artery resistance. Glomerulosclerosis increased (26.1 ± 4.6 vs. 7.3 ± 1.6%, P < 0.05), glomerular CD31 expressions decreased while α-SMA expression increased in DSH group. Immunofluorescence staining showed that CD31 and α-SMA co-expressed in glomeruli of the DSH group. The degree of glomerulosclerosis negatively correlated with CD31 expressions (r = -0.823, P < 0.01) but positively correlated with α-SMA expressions (r = 0.936, P < 0.01)., Conclusions: We demonstrated that a high-salt diet led to glomerulosclerosis involving the EndMT process, which played an essential role in glomerulosclerosis in hypertensive Dahl-SS rats., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P <0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight ( β =-47.9, 95% CI :-94.3- -1.6; P =0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR =0.5, 95% CI : 0.3-0.9; P =0.021) and low birth weight infants ( OR =0.6, 95% CI : 0.4-0.9; P =0.020). Increased homocysteine level was associated with increased risks of SGA ( OR =1.5, 95% CI : 1.0-2.2; P =0.029) and inconsistent growth in twin fetuses ( OR =1.9, 95% CI : 1.0-3.7; P =0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P <0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy ( β =-65.9, 95% CI :-110.6- -21.1; P =0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P <0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.

Electrochemical CO 2 reduction in acidic electrolytes is a promising strategy to achieve high utilization efficiency of CO 2 . Although alkali cations in acidic electrolytes play a vital role in suppressing hydrogen evolution and promoting CO 2 reduction, they also cause precipitation of bicarbonate on the gas diffusion electrode (GDE), flooding of electrolyte through the GDE, and drift of the electrolyte pH. In this work, we realize the electroreduction of CO 2 in a metal cation-free acidic electrolyte by covering the catalyst with cross-linked poly-diallyldimethylammonium chloride. This polyelectrolyte provides a high density of cationic sites immobilized on the surface of the catalyst, which suppresses the mass transport of H + and modulates the interfacial field strength. By adopting this strategy, the Faradaic efficiency (FE) of CO reaches 95 ± 3% with the Ag catalyst and the FE of formic acid reaches 76 ± 3% with the In catalyst in a 1.0 pH electrolyte in a flow cell. More importantly, with the metal cation-free acidic electrolyte the amount of electrolyte flooding through the GDE is decreased to 2.5 ± 0.6% of that with alkali cation-containing acidic electrolyte, and the FE of CO maintains above 80% over 36 h of operation at -200 mA·cm -2 ., (© 2023. Springer Nature Limited.)

Background: Multiple carpometacarpal fractures and dislocations are rare. This case report describes a novel multiple carpometacarpal injury, namely, 'diagonal' carpometacarpal joint fracture and dislocation., Case Presentation: A 39-year-old male general worker sustained a compression injury to his right hand in the dorsiflexion position. Radiography indicated a Bennett fracture, hamate fracture, and fracture at the base of the second metacarpal. Subsequent computed tomography and intraoperative examination confirmed an injury to the first to fourth carpometacarpal joint along a diagonal line. The normal anatomy of the patient's hand was successfully restored via open reduction combined with Kirschner wire and steel plate fixation., Conclusion: Our findings highlight the importance of taking the injury mechanism into account to avoid a missed diagnosis and to choose the best treatment approach. This is the first case of 'diagonal' carpometacarpal joint fracture and dislocation to be reported in the literature., (© 2023. The Author(s).)

Objective: To explore the status quo and influencing factors of feeding behaviors of micronutrient powders (MNP), or yingyangbao in Pinyin, the Chinese Romanization system, of baby caregivers in remote rural areas of Sichuan Province., Methods: In 2019, caregivers of babies aged 6 to 24 months from 6 counties of Sichuan Province were selected as the respondents of the survey through a multistage cluster random sampling method. Data concerning the baby caregivers' attitude of behavior, subjective norms, behavioral intention, and feeding behaviors about MNP feeding were collected with a questionnaire through a structured interview. Based on the theory of reasoned action, a structural equation model was constructed to explore the influencing factors of feeding behaviors., Results: A total of 1002 valid samples were included in the study. The effective feeding rate of MNP among the baby caregivers was 55.49%. The results of model analysis suggested that attitude of behavior ( β direct =0.212, 95% CI : 0.105-0.327), subjective norm ( β direct =0.123, 95% CI : 0.016-0.228), and behavioral intention ( β direct =0.162, 95% CI : 0.093-0.224) could have a significant direct impact on MNP feeding behaviors. Behavior attitude ( β indirect =0.044, 95% CI : 0.023-0.073) and subjective norms ( β indirect =0.018, 95% CI : 0.001-0.040) could have a significant indirect impact on MNP feeding behaviors through the intermediary of behavioral intention. Among the three theoretical elements, attitude of behavior had the largest total effect on the feeding behavior ( β total =0.256, 95% CI : 0.148-0.366)., Conclusion: The effective feeding rate of MNP among baby caregivers in remote rural areas of Sichuan Province is low. The attitude of behavior and subjective norms of caregivers may have a direct impact on their feeding behavior, and both attitude of behavior and subjective norms can have an indirect impact on the feeding behavior through the intermediary of behavioral intention. The influence of attitude of behavior attitude on feeding behavior is greater than that of subjective norms. Future intervention plans for promoting effective MNP feeding should incorporate health education for baby caregivers and their important social relations. Thus, baby caregivers' attitude and willingness for MNP feeding will be strengthened and the effective feeding rate of MNP will be improved accordingly., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Transcutaneous electrical nerve stimulator (TENS) has been demonstrated to be beneficial in glycemic control in animal models, but its application in humans has not been well studied. We randomly assigned 160 patients with type 2 diabetes on oral antidiabetic drugs 1:1 to the TENS study device (n = 81) and placebo (n = 79). 147 (92%) randomized participants (mean [SD] age 59 [10] years, 92 men [58%], mean [SD] baseline HbA 1c level 8.1% [0.6%]) completed the trial. At week 20, HbA 1c decreased from 8.1% to 7.9% in the TENS group (- 0.2% [95% CI - 0.4% to - 0.1%]) and from 8.1% to 7.8% in the placebo group (- 0.3% [95% CI - 0.5% to - 0.2%]) (P = 0.821). Glycemic variability, measured as mean amplitude of glycemic excursion (MAGE) at week 20 were significantly different in the TENS group vs. the placebo group (66 mg/dL [95% CI 58, 73] vs. 79 mg/dL [95% CI 72, 87]) (P = 0.009). Our study provides the clinical evidence for the first time in humans that TENS does not demonstrate a statistically significant HbA 1c reduction. However, it is a safe complementary therapy to improve MAGE in patients with type 2 diabetes., (© 2023. The Author(s).)

Objectives: Excessive accumulation of adipose tissue may accelerate brain aging, but the underlying mechanisms are poorly understood. Several adiposity indices were proposed to assess obesity, while their linkage with brain health in older adults remained unclear. Here we aimed to examine the associations of adiposity indices with global and regional cerebral blood flow (CBF) in older adults, while considering insulin resistance., Design: This was a cross-sectional population-based study that included older adults derived from the baseline participants in the ongoing Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) study., Setting and Participants: The study included 103 Chinese rural-dwelling older adults (age≥60 years; 69.9% women) who underwent brain magnetic resonance imaging scans., Methods: We estimated eight adiposity indices based on anthropometric measures. We automatically quantified global and regional CBF using the arterial spin labeling scans. Insulin resistance was assessed using the triglyceride-glucose index and then dichotomized into high and low levels according to the median. Data were analyzed using general linear model and voxel-wise analysis., Results: Of the eight examined adiposity indices, only higher waist-to-height ratio (WHtR) and body roundness index (BRI) were associated with reduced global CBF (multivariable-adjusted β-coefficients and 95%CI: -1.76; -3.25, -0.27 and -1.77; -3.25, -0.30, respectively) and hypoperfusion in bilateral middle temporal gyri, angular gyri and superior temporal gyri, left middle cingulum and precuneus (P<0.05). There were statistical interactions of WHtR and BRI with levels of insulin resistance on CBF, such that the significant associations of higher WHtR and BRI with lower global and regional CBF existed only in people with high insulin resistance (P<0.05)., Conclusion: Higher WHtR and BRI are associated with cerebral hypoperfusion in older adults, especially in people with high insulin resistance. This may highlight the pathological role of visceral fat in vascular brain aging., Competing Interests: All authors declare no conflicts of interest.

Microtubules are the fundamental part of the cell cytoskeleton intimately involving in cell proliferation and are superb targets in clinical cancer therapy today. Microtubule stabilizers have become one of the effectively main agents in the last decades for the treatment of diverse cancers. Taccalonolides, the highly oxygenated pentacyclic steroids isolated from the genus of Tacca , are considered a class of novel microtubule-stabilizing agents. Taccalonolides not only possess a similar microtubule-stabilizing activity as the famous drug paclitaxel but also reverse the multi-drug resistance of paclitaxel and epothilone in cellular and animal models. Taccalonolides have captured numerous attention in the field of medicinal chemistry due to their variety of structures, unique mechanism of action, and low toxicity. This review focuses on the structural diversity, semi-synthesis, modification, and pharmacological activities of taccalonolides, providing bright thoughts for the discovery of microtubule-stabilizing drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Du, Gao, Xu, Zheng, Liu and Lei.)

Though a number of on-off or off-on fluorescent probes have been developed for the detection of thiophenol by using its unique recognition groups, such as 2, 4-dinitrophenyl ether, 2, 4-dinitrophenyl sulfonamide, and 2, 4-dinitrophenyl sulfonate, up to now, there are few probes that can detect thiophenol by the proportional fluorescence signal. We developed a ratiometric fluorescent probe with coumarin pyridine derivative as fluorophore and 2, 4-dinitrophenyl ether moiety as the sensing unit which could be used to detect thiophenol derivatives by the aromatic nucleophilic substitution reaction. This probe (CPBPN) displayed significant change in fluorescence ratio (256 fold) to result in a more reliable analysis by self-calibration and a relatively low detection limit of 24 nM toward 4-methylthiophenol (MTP) within 30 min to achieve more sensitivity. Besides, the probe was also applied to detect the presence of thiophenol derivatives in actual water samples and fluorescence imaging in living cells. The present work is of great importance for monitoring environmental pollutants and studying their biological function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Given that the prevalence rate of type 2 diabetes mellitus (T2DM) continues to increase, it is important to find an effective method to prevent or treat this disease. Previous studies have shown that dietary intervention with a slowly digestible carbohydrate (SDC) diet can improve T2DM with almost no side effects. However, the underlying mechanisms of SDC protect against T2DM remains to be elucidated., Methods: The T2DM mice model was established with a high-fat diet and streptozocin injection. Then, SDC was administered for 6 weeks. Bodyweight, food intake, organ indices, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), homeostasis model assessment for insulin resistance (HOMA-IR), and other biochemical parameters were measured. Histopathological and lipid accumulation analyses were performed, and the glucose metabolism-related gene expressions in the liver and skeletal muscle were determined. Lastly, colonic microbiota was also analyzed., Results: SDC intervention alleviated the weight loss in the pancreas, lowered blood glucose and glycosylated hemoglobin levels, and improved glucose tolerance and HOMA-IR. SDC intervention improved serum lipid profile, adipocytokines levels, and lowered the lipid accumulation in the liver, subcutaneous adipose tissue, and epididymal visceral adipose tissue. In addition, SDC intervention increased the expression levels of IRS-2 and GLUT-2 in liver tissues and elevated GLUT-4 expression levels in skeletal muscle tissues. Notably, SDC intervention decreased the Bacteroidetes/Firmicutes ratio, increased Desulfovibrio and Lachnospiraceae genus levels, and inhibited the relative abundance of potentially pathogenic bacteria., Conclusions: SDC intervention can improve hyperglycemia and hyperlipidemia status in diabetic mice, suggesting that this intervention might be beneficial for T2DM., Competing Interests: W-TC, H-QL, YL, and H-TF are employed by Inner Mongolia Dairy Technology Research Institute Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Gu, Chuang, Du, Zhang, Lu, Xu, Li, Liu, Feng, Li and Qin.)

Aim: To summarize the data of epidemiological studies on cataract prevalence over 50 years old in urban and rural areas of China from 2000 to 2020, and to analyze the prevalence of cataract and operation rate in China., Methods: By searching PubMed, EMBASE, Web of Science, Wanfang Data and CNKI, Chinese and English literatures on the prevalence of cataract in China were retrieved, and the relevant characteristic data were extracted. Then, Stata v15SE software was used for Meta-analysis and heterogeneity test. According to the results of heterogeneity, the corresponding effect models were selected to combine the extracted data., Results: A total of 20 studies were included in this study, with a total of 111 434 cases. Meta-analysis showed heterogeneity. According to the random effect model, the overall prevalence of cataract in Chinese people over 50 years old was 27.45%, that in rural was 28.79%, and that in urban was 26.66%. The overall coverage rate of cataract surgery was 9.19%., Conclusion: The prevalence of cataract is high in China, and there is still room for improvement in surgical coverage, so it is very important to promote cataract screening and prevention., (International Journal of Ophthalmology Press.)

This work presented a benzothiazole-based fluorescent probe for the detection of benzenethiol derivatives using 2, 4-dinitrobenzene moiety as a sensing unit. This probe (NCABT) was able to instantaneously respond to 4-methylbenzenethiol (MTP) within 5 min. In detecting MTP, this probe displayed a low limit of detection (49 nM). Furthermore, the probe has been proved to have the potential to detect benzenethiol derivatives with electron-donating group in real water samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To determine the impact of visual impairment (VI) on health-related quality of life (HRQoL) and to compare the health burden of VI in different areas in mainland China., Methods: A cohort of 6830 people from rural villages and a cohort of 3251 people from an urban city were included to receive comprehensive ophthalmologic examinations and complete the European Quality of Life-5 Dimensions 3 Levels (EQ-5D-3L) questionnaire. For urban and rural populations, a unified VI grouping standard was adopted: the eyes were classified into normal group, mild-moderate group, and severe group according to WHO standards, and then divided into 6 groups considering both eyes. We estimated the effects of VI on the EQ-5D index score using linear regression models and the association between VI and self-reported EQ-5D health problems using logistic regression models. Associations were assessed by the Spearman correlation coefficient., Results: The prevalence of VI and the index scores of EQ-5D-3L for each subgroup of VI were higher for the rural cohort. In these two cohorts, the severity of VI in rural population (Spearman r = 0.205; p < 0.0001) and urban population (Spearman r = 0.164; p < 0.0001) is correlated with the EQ-5D index score. In the rural cohort, the difference in index scores with bilateral severe VI compared to those without VI, after adjusting for covariates, was - 0.053 for the rural cohort and - 0.084 for the urban cohort, respectively. In the rural cohort, the odds ratio for bilateral severe VI was 4.39 for mobility, 6.33 for self-care, and 5.88 for usual activities. The incidence of anxiety or depression and pain or discomfort in the urban cohort was greater; the OR for bilateral severe VI in the urban cohort was 4.75., Conclusions: VI has a negative impact on HRQoL in the rural and urban areas of China, especially in urban population. It is also more likely to cause anxiety or depression among the urban cohort, which deserves special attention., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Intestinal injury is a clinical problem related to radiotherapy or accidental exposure to ionizing radiation. This study aimed to investigate the protective effect of p-coumaric acid (CA) against radiation induced intestinal injury., Main Methods: The present study orally administered CA to C57BL/6 male mice at 30 min before total body irradiation and continued for 3 days post irradiation. Then, the mice were sacrificed at day 3.5 or 14 after irradiation, respectively. The blood was collected to analyze the inflammatory cytokines. The antioxidant indexes of jejunum tissues were determined. Hematoxylin and eosin staining and apoptosis analysis was studied to investigate the pathological changes of the jejunum tissues. In addition, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were carried out to determine the changes in mRNA and protein levels of jejunum tissues., Key Findings: Compared with the only irradiated group, treatment with CA improved intestinal morphology and apoptosis, increased the villus height and the ratio of villus height to crypt depth. It also reduced the oxidative stress and inflammatory response. The molecular mechanism analysis showed that CA significantly inhibited the pyroptosis genes (Caspase-1, NLRP3 and AIM2) mRNA expression and improved the intestinal barrier genes expression., Significance: The results suggested that CA ameliorates ionizing radiation-induced intestinal injury by inhibition of oxidative stress, inflammatory response and pyroptosis., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To evaluate the current status of first food supplement and the nutrition of infants and young children in rural areas inhabited by people of Han, Tibetan, and Yi ethnicities in Sichuan Province, and to explore the relationship between the first ever feeding of food supplement and the nutritional status., Methods: Using a multi-stage randomized cluster sampling method, we selected 2 Han counties, 2 Tibetan counties and 2 Yi counties in rural areas of Sichuan Province. These counties were previously defined as economically poor counties, but had since been lifted out of poverty. They were selected for this study before they came out of poverty. Infants and young children of 12-24 months old and their main caregivers from these counties were the subjects of the study. Structured questionnaires were used to collect information concerning the sociodemographic characteristics of infants and young children and their caregivers, and the first complementary feeding for infants and young children. Infant and young children weight scales and length/height tapes were used to collect the weight and length/height data of infants and young children. Unconditional logistic regression was used to analyze the correlation between the behavior of giving supplementary food for the first time to infants and young children and their nutritional status., Results: A total of 1117 pairs of infants and children and their caregivers were investigated. Regarding the time of first supplementary food addition, nearly half of the caregivers in Han areas started adding supplementary food when the infants were 6 months old, accounting for 43.07% (171/397). Most of the caregivers in Yi and Tibetan areas started giving infants and young children supplementary food when they were less than 6 months old, accounting for 77.18% (301/390) and 47.58% (157/330), respectively. In terms of the types of supplementary food added for the first time, caregivers in Han areas mainly used homemade rice cereal, accounting for 41.56% (165/397), caregivers in Tibetan areas mainly used meat, vegetables or fruits and other complementary foods, accounting for 42.12% (139/330), and caregivers in Yi areas mainly used homemade rice cereal, accounting for 46.41% (181/390). The overall malnutrition rate of infants and young children was 28.83% (322/1117) and the malnutrition rate of infants and young children in Han, Tibetan, and Yi areas were 10.58% (42/397), 24.85 (82/330), and 50.77 (198/390), respectively. The regression analysis results show that after controlling for confounding factors, compared with Han areas, it is more likely for infants and young children in Yi areas to be malnourished ( OR =9.49, 95% CI 6.00-15.00). Compared with adding other types of complementary foods for the first time, infants and young children given iron-fortified rice cereal had a lower risk of malnutrition ( OR =0.54, 95% CI 0.29-0.99)., Conclusion: The multi-ethnic rural areas of Sichuan Province had problems that supplementary foods are added too early, and that the types of supplementary foods added for the first time were not appropriate. In addition, the nutritional status of local infants and young children in these areas was causing concerns. The malnutrition problem of infants and young children was especially prominent in the Yi ethnic areas. Adding iron-fortified rice cereal for the first time could reduce the possibility of malnutrition in infants and young children to a certain extent. It is recommended that attention should be given to the health education intervention of the first supplementary food for infants and young children to effectively improve the nutritional status of infants and young children in these areas., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Bladder cancer (BC) is the ninth most common lethal malignancy worldwide. Great efforts have been devoted to clarify the pathogenesis of BC, but the underlying molecular mechanisms remain unclear. To screen for the genes associated with the progression and carcinogenesis of BC, three datasets were obtained from the Gene Expression Omnibus. A total of 37 tumor and 16 non-cancerous samples were analyzed to identify differentially expressed genes (DEGs). Subsequently, 141 genes were identified, including 55 upregulated and 86 downregulated genes. The protein-protein interaction network was established using the Search Tool for Retrieval of Interacting Genes database. Hub gene identification and module analysis were performed using Cytoscape software. Hierarchical clustering of hub genes was conducted using the University of California, Santa Cruz Cancer Genomics Browser. Among the hub genes, kinesin family member 11 (KIF11) was identified as one of the most significant prognostic biomarkers among all the candidates. The Kaplan Meier Plotter database was used for survival analysis of KIF11. The expression profile of KIF11 was analyzed using the ONCOMINE database. The expression levels of KIF11 in BC samples and bladder cells were measured using reverse transcription-quantitative pCR, immunohistochemistry and western blotting. In summary, KIF11 was significantly upregulated in BC and might act as a potential prognostic biomarker. The present identification of DEGs and hub genes in BC may provide novel insight for investigating the molecular mechanisms of BC., (Copyright: © Mo et al.)

N-methyl-D-aspartate receptors (NMDARs) play critical roles in the physiological function of the mammalian central nervous system (CNS), including learning, memory, and synaptic plasticity, through modulating excitatory neurotransmission. Attributed to etiopathology of various CNS disorders and neurodegenerative diseases, GluN2B is one of the most well-studied subtypes in preclinical and clinical studies on NMDARs. Herein, we report the synthesis and preclinical evaluation of two 11 C-labeled GluN2B-selective negative allosteric modulators (NAMs) containing N,N-dimethyl-2-(1H-pyrrolo[3,2-b]pyridin-1-yl)acetamides for positron emission tomography (PET) imaging. Two PET ligands, namely [ 11 C]31 and [ 11 C]37 (also called N2B-1810 and N2B-1903, respectively) were labeled with [ 11 C]CH 3 I in good radiochemical yields (decay-corrected 28% and 32% relative to starting [ 11 C]CO 2 , respectively), high radiochemical purity (>99%) and high molar activity (>74 GBq/μmol). In particular, PET ligand [ 11 C]31 demonstrated moderate specific binding to GluN2B subtype by in vitro autoradiography studies. However, because in vivo PET imaging studies showed limited brain uptake of [ 11 C]31 (up to 0.5 SUV), further medicinal chemistry and ADME optimization are necessary for this chemotype attributed to low binding specificity and rapid metabolism in vivo.

Although it was known that obesity is an independent risk factor for metabolic disorders including diabetes, the factors that link these diseases were obscure. The Hedgehog-interacting protein (Hhip) is a negative regulator in tissue remodeling, and inhibits the proliferation of adipocytes, and promotes their differentiation. In addition, Hhip was positively associated with diabetes. However, the relationship between Hhip and obesity in the human body remains unclear. An analysis of the relationship between Hhip and normal weight, overweight, and obesity levels. Participants receiving a physical checkup were recruited. Anthropometric and biochemical data were collected. Serum Hhip levels were determined by enzyme-linked immunosorbent assay (ELISA). Subjects were classified into normal-weight, overweight, and obese groups based on their body mass index (BMI). The association between Hhip and obesity was examined by multivariate linear regression analysis. In total, 294 subjects who were either of a normal weight ( n = 166), overweight ( n = 90), or obese ( n = 38) were enrolled. Hhip concentrations were 6.51 ± 4.86 ng/mL, 5.79 ± 4.33 ng/mL, and 3.97 ± 3.4 ng/mL in normal-weight, overweight, and obese groups, respectively ( p for trend = 0.032). Moreover, the regression analysis showed that BMI (β = -0.144, 95% confidence interval (CI) = -0.397-0.046, p = 0.013) was negatively associated with Hhip concentrations after adjusting for sex and age. Being overweight (β = -0.181, 95% CI = -3.311-0.400, p = 0.013) and obese (β = -0.311, 95% CI = -6.393-2.384, p < 0.001) were independently associated with Hhip concentrations after adjusting for sex, age, fasting plasma glucose, the insulin level, and other cardiometabolic risk factors. Our results showed that overweight and obese subjects had lower Hhip concentrations than those of normal weight. Being overweight and obese were negatively associated with Hhip concentrations. Hhip might be a link between obesity and diabetes.

Background: Ocular changes are traditionally associated with only a few hepatobiliary diseases. These changes are non-specific and have a low detection rate, limiting their potential use as clinically independent diagnostic features. Therefore, we aimed to engineer deep learning models to establish associations between ocular features and major hepatobiliary diseases and to advance automated screening and identification of hepatobiliary diseases from ocular images., Methods: We did a multicentre, prospective study to develop models using slit-lamp or retinal fundus images from participants in three hepatobiliary departments and two medical examination centres. Included participants were older than 18 years and had complete clinical information; participants diagnosed with acute hepatobiliary diseases were excluded. We trained seven slit-lamp models and seven fundus models (with or without hepatobiliary disease [screening model] or one specific disease type within six categories [identifying model]) using a development dataset, and we tested the models with an external test dataset. Additionally, we did a visual explanation and occlusion test. Model performances were evaluated using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and F1* score., Findings: Between Dec 16, 2018, and July 31, 2019, we collected data from 1252 participants (from the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Sun Yat-sen University, the Department of Infectious Diseases of the Affiliated Huadu Hospital of Southern Medical University, and the Nantian Medical Centre of Aikang Health Care [Guangzhou, China]) for the development dataset; between Aug 14, 2019, and Jan 31, 2020, we collected data from 537 participants (from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University and the Huanshidong Medical Centre of Aikang Health Care [Guangzhou, China]) for the test dataset. The AUROC for screening for hepatobiliary diseases of the slit-lamp model was 0·74 (95% CI 0·71-0·76), whereas that of the fundus model was 0·68 (0·65-0·71). For the identification of hepatobiliary diseases, the AUROCs were 0·93 (0·91-0·94; slit-lamp) and 0·84 (0·81-0·86; fundus) for liver cancer, 0·90 (0·88-0·91; slit-lamp) and 0·83 (0·81-0·86; fundus) for liver cirrhosis, and ranged 0·58-0·69 (0·55-0·71; slit-lamp) and 0·62-0·70 (0·58-0·73; fundus) for other hepatobiliary diseases, including chronic viral hepatitis, non-alcoholic fatty liver disease, cholelithiasis, and hepatic cyst. In addition to the conjunctiva and sclera, our deep learning model revealed that the structures of the iris and fundus also contributed to the classification., Interpretation: Our study established qualitative associations between ocular features and major hepatobiliary diseases, providing a non-invasive, convenient, and complementary method for hepatobiliary disease screening and identification, which could be applied as an opportunistic screening tool., Funding: Science and Technology Planning Projects of Guangdong Province; National Key R&D Program of China; Guangzhou Key Laboratory Project; National Natural Science Foundation of China., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Prostate cancer is one of the most commonly diagnosed cancers and one of the most common causes of cancer-related deaths among men worldwide. Patients who are diagnosed with localized prostate cancer and treated with radical prostatectomy often respond well to therapy. The current standard therapy for prostate cancer involves maximal surgical resection, followed by radiotherapy and chemotherapy. Clarifying the molecular mechanism of tumor proliferation and recurrence becomes more and more important for clinical therapies of prostate cancer., Methods: Quantitative Real-Time PCR and Western-blot were used in the detection of mRNA and protein expression. Lentivirus infection was used to overexpress or knockdown the target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between the two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett's posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis., Results: In this study, we identified that FOXM1 expression was significantly enriched in prostate cancer compared with normal tissue. Additionally, FOXM1 was functionally required for tumor proliferation and its expression was associated with poor prognosis in prostate cancer patients. Mechanically, FOXM1-dependent regulation of EZH2 is essential for proliferation and progression in prostate cancer., Conclusion: Taken together, our data suggest that oncogenic transcription factor FoxM1 is up-regulated in prostate cancer, suggesting that the growth of cancer cells may depend on FOXM1 activity. FOXM1 may serve as a clinical prognostic factor and a therapeutic target for prostate cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Hepatitis C virus (HCV) is one of the main causes of liver fibrosis, chronic hepatitis, and liver cirrhosis. The aim of this study is to determine the prevalence of HCV, age-dependent prevalence and genotypes distribution in a large number of clinical samples in Sichuan area of China., Methods: In the past five years from 2014 to 2018, a total number of 4,508 individuals received the serum HCV-RNA analysis in the Sichuan Provincial People's Hospital. Viral nucleic acid was extracted from the serum samples and amplified using COBAS AmpliPre/COBAS TaqMan Detection Platform. Five HCV genotypes (1b, 2a, 3a, 3b, and 6a) of serum samples from 469 HCV positive individuals collected from 2016 to 2018 were analyzed using the PCR-fluorescence probe technique., Results: A total of 1,668 individuals had positive results by high precision HCV-RNA quantitative technique, corresponding to a crude prevalence of 37.0% (95% confidence interval: 33.6 - 40.3%). The majority of HCV positive individuals were aged over 41 years, accounting for 80.7% (1,346/1,668, CI: 72.3 - 87.1%). Among the nine age groups, the 41 - 50-year age group had the highest HCV prevalence of 29.8% (497/1,668, CI: 25.6 - 32.3%). Of the 469 HCV-RNA positive serum samples collected in 2016 - 2018, genotype 1b was the most frequent type found in 357 individuals, corresponding to a prevalence of 76.1% (CI: 72.3 - 80.0%)., Conclusions: Positive rates of HCV in the years of 2014 to 2018 showed a downward trend year by year, of which a majority of positive cases were aged over 41 years. HCV was distributed with multi-genotype features while genotype 1b yielded a very high prevalence in the Sichuan area. The results have potential for prevention and treatment of HCV infection, as well as epidemiological research.

Background: Whether ischemic stroke per se, rather than older age or additional comorbidities, accounts for the adverse prognosis of heart failure (HF) is uncertain. The present study examineed the intrinsic association of ischemic stroke with outcomes in a propensity-matched cohort.Methods and Results:Of 1,351 patients hospitalized with HF, 388 (28.7%) had prior ischemic stroke. Using propensity score for prior ischemic stroke, estimated for each patient, a matched cohort of 379 pairs of HF patients with and without prior ischemic stroke, balanced on 32 baseline characteristics was assembled. At 30 days, prior ischemic stroke was associated with significantly higher risks of the combined endpoint of all-cause death or readmission (hazard ratio [HR]: 1.91; 95% confidence interval [CI]: 1.38 to 2.65; P<0.001), all-cause death (HR: 2.08; 95% CI: 1.28 to 3.38; P=0.003), all-cause readmission (HR: 2.67; 95% CI: 1.78 to 4.01; P<0.001), and HF readmission (HR: 2.11; 95% CI: 1.19 to 3.72; P=0.010). Prior ischemic stroke was associated with a significantly higher risk of all 4 outcomes at both 6 months and 1 year., Conclusions: Prior ischemic stroke was a potent and persistent risk predictor of death and readmission among patients with HF after accounting for clinical characteristics.

miR-382-3p can regulate apoptosis through multiple pathways, but the mechanism remains unknown. In this experiment, we explored whether miR-382-3p can modulate the N-methyL-D-aspartate (NMDA)- induced HT22 cell apoptosis by regulating the RhoC/ROCK1 signaling pathway. An excitatory neurotoxicity model of HT22 cells was induced in vitro with 2 mmol/L NMDA. The cells were divided into normal control, NMDA-induced, NMDA + miR-382-3p mimic, and NMDA + miR-382-3p inhibitor groups. The 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method, Real-time PCR, Western blot, and flow cytometry were performed to investigate the mechanisms. The results found that NMDA can increase the oxidative stress of HT22 cells in a dose-dependent manner, downregulate the expression of miR-382-3p, upregulate the expression of mRNA and protein abundance of ROCK1 and RhoC, increase the expression levels of proapoptotic proteins Bax, Caspase-3, and Caspase-9, increase the apoptosis of HT22 cells, and reduce the activity and survival rate of HT22 cells. Compared with the NMDA-induced group, the miR-382-3p mimic-transfected HT22 cells increased the expression of miR- 382-3p, reduced the expression of the mRNA and protein abundance of ROCK1 and RhoC, inhibited the expression of proapoptotic proteins Bax, Caspase-3, and Caspase-9, reduced the apoptosis of HT22 cells, and increased the activity and survival rate of HT22 cells. The results suggest that increasing the expression of miR-382-3p can inhibit the activity of the RhoC/ROCK1 signaling pathway, reduce the expression of proapoptotic proteins, reduce the oxidative stress and apoptosis of HT22 cells, and increase the activity and survival rate of HT22 cells., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

No data are available on the serum metabolomics and lipidomics profiles of people with asymptomatic intracranial arterial stenosis. We explored the characteristic metabolites of individuals with asymptomatic severe intracranial arterial stenosis (asICAS) using untargeted serum metabolomics and lipidomics analyses based on ultra-high-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). This case-control study included 25 participants with asICAS and 25 age- and sex-matched controls free of asICAS, who were all diagnosed by using magnetic resonance angiography and derived from the same population-based study. Serum metabolomics and lipidomics profiles were determined using UPLC-HRMS, and possible biomarker metabolites were identified. Compared with the control group, the asICAS group showed higher levels of free choline, glycerophosphocholine, uracil, taurine, and four peptide molecules and lower levels of free fatty acids, hydroxydodecanedioic acid, hydroxy valeryl carnitine, hydroxytetradecanedioic acid, and two sphingomyelin molecules. The serum metabolomics and lipidomics profiles for people with asICAS are characterized by abnormal metabolism of sphingomyelin, taurine/hypotaurine, pyrimidine, and protein (peptide). The biological changes in asICAS may mainly involve taurine/hypotaurine, glycerophospholipid, and sphingolipid metabolism pathways. Biofunctional analysis indicated that these differential metabolites were correlated with metabolic diseases such as early myocardial injury, heart failure, and diabetes.

Background: Many technology-assisted innovations have been used to manage disease. However, most of these innovations are not broadly used by older adults due to their cost. Additionally, disease management through technology-assisted innovations has not been compared with other interventions., Objective: In this study, we tested the employment of a free and widely used social and communication app to help older adults with diabetes manage their distress and glycemic control. We also compared the effectiveness of the app with 2 other methods, namely telephone and conventional health education, and determined which subgroup experiences the most effects within each intervention., Methods: Adults aged ≥50 years with type 2 diabetes were recruited from Southern Taiwan (N=231) and were allocated to different 3-month interventions. Informed consent was obtained at the Ministry of Science and Technology and approved by the National Cheng Kung University Hospital Institutional Review Board (No. A-ER-102-425)., Results: Participants in the mobile-based group had significant reductions in hemoglobin A1c compared with the telephone-based and usual care groups (mean changes of -0.4%, 0.1%, and 0.03%, respectively; P=.02). Diabetes-specific distress decreased to a greater extent in the mobile-based group compared to the other 2 groups (mean changes of -5.16, -3.49, and -2.44, respectively, P=.02). Subgroup analyses further revealed that the effects on reducing blood glucose levels in the social and communication app groups were especially evident in patients with lower distress scores, and diabetes-related distress was especially evident in participants who were younger than 60 years or had higher educational levels., Conclusions: The findings of this study inform more flexible use of social and communication apps with in-person diabetes education and counselling., (©Ching-Ju Chiu, Yung-Chen Yu, Ye-Fong Du, Yi-Ching Yang, Jou-Yin Chen, Li-Ping Wong, Chanuantong Tanasugarn. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 02.06.2020.)

Background: Severe acute pancreatitis (SAP) is associated with high morbidity and mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown obvious protective effect on SAP. However, little is known about the underlying mechanism. The objective of this study is to unravel the role and regulatory mechanism of miR-181a-5p in BMSCs-mediated pancreatic repair., Methods: BMSCs were isolated from Sprague-Dawley rats and characterized by flow cytometry and Oil Red O staining. Sodium taurocholate- and caerulein-induced models were used as SAP models in vivo and in vitro, respectively. Pancreatic injury were evaluated by H&E and histopathological analysis, as well as by measuring levels of amylase, lipase and cytokines. qRT-PCR and western blotting were performed to detect the level of miR-181a-5p and the protein levels of PTEN/Akt, respectively. ELISA was conducted to detect the levels of TNF-α, IL-1β, IL-6, angiopoietin, IL-4, IL-10 and TGF-β1. The apoptotic rate of AR42J cells was quantitated by concurrent staining with Annexin-V-FITC and PI., Results: BMSCs significantly attenuated pancreatic injury in SAP rats by reducing inflammatory infiltration and necrosis, and this effect was abolished by CXCR4 agonist AMD3100. ADM3100 exhibited more severe pancreatic injury and decreased miR-181a-5p levels in the pancreas and serum compared to SAP group. Overexpression of miR-181a-5p in BMSCs (BMSCs-miR-181a-5p) markedly potentiated the protective effect of BMSCs by reducing histological damage and levels of amylase and lipase. Moreover, BMSCs-miR-181a-5p dramatically reduced levels of angiopoietin, TNF-α, IL-1β and IL-6, but induced the levels of IL-4 and IL-10. In caerulein-treated AR42J cells, co-culturing of BMSCs-miR-181a-5p alleviated caerulein-induced increase of amylase and lipase, and apoptosis via PTEN/Akt/TGF-β1 signaling., Conclusion: BMSCs alleviate SAP and reduce inflammatory responses and apoptosis by secreting miR-181a-5p to target PTEN/Akt/TGF-β1 signaling. Hence, BMSCs-miR-181a-5p could serve as potential therapeutic target for SAP., (Copyright © 2019. Published by Elsevier Inc.)

Hyperphosphorylated tau is one of the key characteristics of Alzheimer's disease (AD), and tau pathology correlates with cognitive impairment in AD better than amyloid-β (Aβ) pathology. Thus, a complete understanding of the relevant factors involved in tau phosphorylation is important for AD treatment. APOEɛ4, the strongest genetic risk factor for AD, was found to be involved in tau pathology in frontotemporal dementia. This result indicated that apolipoprotein E (ApoE) may also participate in tau phosphorylation in AD. In the present study, we injected Aβ oligomer (AβO) into the lateral ventricles of wild-type (WT) mice and apoE-/- mice to test the process of tau phosphorylation in the acute phase. We found that the phosphorylated tau and phosphokinase levels were higher in WT mice than in apoE-/- mice. These phenomena were also confirmed in vitro. ApoE ɛ4-treated apoE-/- neurons exhibited more phosphorylated tau than ApoE ɛ2- and ApoE ɛ3-treated neurons. We also found that AβO induced more serious inflammation in WT mice and in ApoE-positive cultured neurons. Anti-inflammatory treatment reduced the phosphorylated tau level induced by AβOs in ApoE-positive neurons. These results suggest that ApoE may facilitate the phosphorylation of tau induced by AβO via inflammation.

Obesity is a public health problem that has raised concerns worldwide and is often associated with hepatic steatosis. Hepassocin is a novel hepatokine that causes hepatic steatosis and induces insulin resistance (IR). However, the role of hepassocin in obesity remains obscure. Thus, the aim of this study was to investigate the relationship between hepassocin levels and obesity. In total, 371 subjects who had a normal weight (NW), were overweight, or were obese were enrolled. We found that hepassocin levels in subjects who were overweight (6,705 ± 1,707 pg/ml) or obese (7,335 ± 2,077 pg/ml) were significantly higher than those of subjects with a NW (5,767 ± 1,500 pg/ml) (p < .001, test for trend). A multiple linear regression analysis showed that the body-mass index, waist circumference, nonalcoholic fatty liver disease, and homeostatic model assessment of IR were independently associated with hepassocin after adjusting for age, sex, high-sensitivity C-reactive protein, systolic blood pressure, high-density lipoprotein-cholesterol, log triglycerides, alanine transaminase, and the estimated glomerular filtration rate. This study provides evidence that subjects who were overweight or obese had significantly higher hepassocin levels than those with a NW. Hepassocin may be a useful biomarker in managing obesity and its related metabolic dysregulation., (© 2019 International Union of Biochemistry and Molecular Biology.)

Background: Prostate cancer remains one of the most common and deadliest forms of cancer, generally respond well to radical prostatectomy and associated interventions, up to 30% of individuals will suffer disease relapse. Although BUB1B was found to be essential for cell growth and proliferation, even in several kinds of tumor cells, the specific importance and mechanistic role of BUB1B in prostate cancer remain unclear., Methods: Quantitative Real-Time PCR and Western-blot were used in the detection of mRNA and protein expression. Lentivirus infection was used to overexpression or knock down the target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between the two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett's posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis., Results: In the present report, we found BUB1B expression to be highly increased in prostate cancer tissues relative to normal controls. We further found BUB1B to be essential for efficient tumor cell proliferation, and to correlate with poorer prostate cancer patient outcomes. From a mechanistic perspective, the ability of BUB1B to regulate MELK was found to be essential for its ability to promote prostate cancer cell proliferation., Conclusion: Altogether, our data suggest that BUB1B is up-regulated in prostate cancer, suggesting that the growth of cancer cells may depend on BUB1B-dependent regulation of MELK transcription. BUB1B may serve as a clinical prognostic factor and a druggable target for prostate cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To investigate the causes of poor incision healing after total knee arthroplasty(TKA) and to propose active preventive and therapeutic measures., Methods: Total 284 patients undergoing unilateral TKA from September 2016 to June 2018 were enrolled in the study and divided into control group and observation group. Firstly, 150 patients with unilateral TKA from September 2016 to June 2017 were retrospectively analyzed and included in the control group. There were 41 males and 109 females, with an average age of(63.5±7.2) years old. The causes of poor incision healing were discussed about patients themselves and surgical techniques. After analyzing, improvement measures were proposed. Total 134 patients with TKA from July 2017 to June 2018 were included in the observation group. There were 36 males and 98 females, with an average age of(62.4±8.9) years old. The patients in the observation group were treated with improved treatment strategies., Results: Nine patients(6%) had poor incision healing in the control group and 1 patient (0.75%) had poor incision healing in the observation group. The incidence of poor incision healing was significantly different between the two groups ( χ ²=5.750, P <0.01)., Conclusions: In order to prevent the poor incision healing after TKA, perioperative management and the operation techniques including stable, accurate, rapid and clean skills should be improved, leading to reduce the complications of incision and improve the recovery rate of patients., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Although researchers have determined that attaining high grain yields of winter wheat depends on the spike number and the shoot biomass, a quantitative understanding of how phosphorus (P) nutrition affects spike formation, leaf expansion and photosynthesis is still lacking. A 3-year field experiment with wheat with six P application rates (0, 25, 50, 100, 200, and 400 kg P ha -1 ) was conducted to investigate this issue. Stem development and mortality, photosynthetic parameters, dry matter accumulation, and P concentration in whole shoots and in single tillers were studied at key growth stages for this purpose. The results indicated that spike number contributed the most to grain yield of all the yield components in a high-yielding (>8 t/ha) winter wheat system. The main stem (MS) contributed 79% to the spike number and tiller 1 (T1) contributed 21%. The 2.7 g kg -1 tiller P concentration associated with 15 mg kg -1 soil Olsen-P at anthesis stage led to the maximal rate of productive T1s (64%). The critical shoot P concentration that resulted in an adequate product of Pn and LAI was identified as 2.1 g kg -1 . The thresholds of shoot P concentration that led to the maximum productive ability of T1 and optimal canopy photosynthetic capacity at anthesis were very similar. In conclusion, the thresholds of soil available P and shoot P concentration in whole plants and in single organs (individual tillers) were established for optimal spike formation, canopy photosynthetic capacity, and dry matter accumulation. These thresholds could be useful in achieving high grain yields while avoiding excessive P fertilization.

Background: This study aimed to determine whether CD44 polymorphisms were correlated with hepatocellular carcinoma (HCC) and to reveal a new potential target for early prediction, prevention, and diagnosis of HCC., Method: This study involved 96 cases with chronic hepatitis B (CHB), 96 cases with hepatitis B virus-related liver cirrhosis (LC), 204 cases with HCC related to the hepatitis B virus, and 210 healthy controls. The genotype of rs8193 was determined using the restriction fragment length polymorphism method, while the genotypes of rs10836347 and rs13347 were determined by direct sequencing., Results: The results showed that patients with the CD44 rs13347 TT and T allele polymorphisms exhibited higher risks of LC than those carrying the CC genotype and C allele. The CD44 rs13347 CT and TT genotypes and T allele were significantly associated with an increased risk of HCC after adjusting for gender, age, smoking, and alcohol consumption (for CT: odds ratio [OR] = 1.626, 95% confidence interval [CI] = 1.057-2.500, P = .027; for TT: OR = 1.965, 95% CI = 1.043-3.702, P = .037; and for T: OR = 1.461, 95% CI = 1.091-1.956, P = .011). In the rs13347 site of the female population, the CT and TT genotypes were related to the high occurrence of HCC. In the population aged ≥50 years, carriers of the CD44 rs13347 CT and TT alleles were more susceptible to HCC compared with CC carriers. Those who consumed alcohol who carried the rs10836347 CT genotype exhibited a risk factor for HCC., Conclusion: For the CD44 rs13347 site, mutations in the T allele might be a risk factor for HCC., (© 2019 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

The effects of red/blue=3/1 [R/B=3/1(9/3), as control, CK 1 ], white light (W, as control, CK 2 ), and combined light of red, blue and white [R/B/W=3/1/1 (9/3/3), T 1 ; R/B/W=9/3/8, T 2 ; R/B/W=3/1/6 (9/3/18), T 3 ; R/B/W=3/1/16 (9/3/48), T 4 ] on the growth, root development, quality and yield of eggplants were examined to provide theoretical and technical support for intensive and high-efficient light supplement and eggplant seedlings cultivation, using LED to accurately regulate light environment and 'Gailiangdalong' eggplant, based on the previous findings of the benefits of R/B=3/1 to the cultivation of eggplant seedlings. The results showed that R/B/W=9/3/8 treatment significantly increased plant height, stem diameter, seedling index, shoot dry weight, root dry weight, root development, anthocyanins and flavonoids content in eggplant peels and early yield. Root/shoot, total phenolic content in eggplant peels and soluble sugar content in pulps under R/B/W=3/1/1 treatment were significantly higher than those of other treatments. Total leaf area and free amino acid content in pulps were higher under R/B/W=3/1/6 treatment. The soluble protein content in pulps was higher under R/B/W=3/1/16 treatment. In summary, combined LED light of red, blue and white could improve the quality of eggplant seedlings and the yield and quality of eggplant fruits, with R/B/W=9/3/8 treatment being the best one in our study.

We report here the coupling reactions between vinyl/aryl and alkyl C-O electrophiles that can be derived from chemical feedstocks and naturally occurring functional groups. This method provides an efficient approach to the synthesis of a wide range of functionalized, and/or secondary alkyl substituted cycloalkenes. These compounds are difficult to produce by conventional methods. The reaction proceeds with broad substrate scope, and tolerates various functional groups such as alcohol, aldehyde, ketone, ester, amide, alkene, alkyne, heterocycles, organotin and organosilicon compounds. The synthetic utility of this method has been demonstrated by providing facile access to important building blocks. We also demonstrated the possibility to apply this method for late-stage modification of peptides. A broad range of functionalized alkyl groups could be selectively introduced into tyrosine in peptides via C-C bond formation, which has been a challenge to the existing procedures., (This journal is © The Royal Society of Chemistry 2019.)

Objective: To compare osseous outcomes of block and cancellous iliac bone grafting in older unilateral alveolar cleft patients., Design: Retrospective and observational follow-up study., Setting: Cleft Lip and Palate Centre, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China., Patients: Forty-five nonsyndromic patients with unilateral complete alveolar cleft were enrolled in this study (25 patients in block bone graft group and 20 patients in cancellous bone graft group)., Interventions: In cancellous bone graft group, the alveolar cleft was filled with iliac cancellous bone particulate. In group of block bone graft, the harvested bone block was trimmed and fixed in alveolar defect., Main Outcome Measures: A novel method was proposed to investigate the volume and density of residual bone graft at 1-week, 3- and 6-month, 1- and 2-year postoperatively based on cone beam computed tomography scans., Results: No difference in bone graft volume was found between 2 groups at 1-week and 3-month postoperatively; however, the residual volume of block bone graft group was significantly larger than that of cancellous bone graft group at 6-month, 1- and 2-year postoperatively. The bone density of block bone graft group was lower at 1-week and 3-month postoperatively but was comparable at 6-month, 1- and 2-year postoperatively. Our method was reliable and accurate to identify the range of residual bone graft when the boundary of grafted bone could not be identified clearly., Conclusion: Block bone graft could achieve comparable bone density and retain a greater amount of residual bone comparing to cancellous bone graft.

The degradation rates and kinetics of one commonly used iodinated contrast medium, iohexol, were investigated and compared during ultraviolet (UV) photolysis, UV/H 2 O 2 and UV/S 2 O 8 2- advanced oxidation processes (AOPs). Results indicate that the iohexol degradation rate increased in the order of UV/H 2 O 2  < UV irradiation < UV/S 2 O 8 2- and followed pseudo-first-order kinetics. Increasing persulfate concentration significantly increased iohexol degradation rate, whereas increasing H 2 O 2 concentration caused reverse effect. Radical scavenging test results show that UV photolysis, OH and radicals all contributed to iohexol degradation during UV/S 2 O 8 2- , but OH was the main contributor during UV/H 2 O 2 and was consumed by excess H 2 O 2 . The kinetic models of iohexol degradation by both AOPs were developed, and the reaction rate constants with OH and were calculated as 5.73 (±0.02) × 10 8 and 3.91 (±0.01) × 10 10  M -1  s -1 , respectively. Iohexol degradation rate remained stable at pH 5-9 during UV irradiation and UV/H 2 O 2 , but gradually decreased at pH 5-7 and remained stable at pH 7-9 during UV/S 2 O 8 2- . The presence of anions displayed inhibitory effects on iohexol degradation during UV/S 2 O 8 2- in the order of Cl - >HCO 3 - ≫ SO 4 2- . UV/S 2 O 8 2- AOP exhibited high degradation efficiency and stability on the basis of UV irradiation, which can be applied as a promising degradation method for iohexol. UV/S 2 O 8 2- AOP can effectively mineralize iohexol to CO 2 but promoted the generation of toxic iodoform (CHI 3 ), and the subsequent chlorination had the potential to reduce the content of disinfection by-products; therefore, further evaluation of possible environmental hazards is warranted., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Accumulating evidence has shown that tauroursodeoxycholic acid (TUDCA) is neuroprotective in different animal models of neurological diseases. However, whether TGR5 agonist TUDCA can improve lipopolysaccharide (LPS)-induced cognitive impairment in mice is less clear. Using a model of cognitive impairment with LPS (2.0 μg) we investigated the effects of TUDCA (200 or 400 μg) on cognitive dysfunction and neurotoxicity in mice. Both Morris water maze and Y-maze avoidance tests showed that TUDCA treatment significantly alleviated LPS-induced behavioral impairments. More importantly, we found that TUDCA treatment reversed TGR5 down-regulation, prevented neuroinflammation via inhibiting NF-κB signaling in the hippocampus of LPS-treated mice. Additionally, TUDCA treatment decreased LPS-induced apoptosis through decreasing TUNEL-positive cells and the overexpression of caspase-3, increasing the ratio of Bcl-2/Bax. TUDCA treatment also ameliorated synaptic plasticity impairments by increasing the ratio of mBDNF/proBDNF, the number of dendritic spines and the expression of synapse-associated proteins in the hippocampus. Our results indicated that TUDCA can improve cognitive impairment and neurotoxicity induced by LPS in mice, which is involved in TGR5-mediated NF-κB signaling., (Copyright © 2019. Published by Elsevier B.V.)

Time is a continuous, homogeneous, one-way, and independent signal that cannot be modified by human will. The mechanism of how the brain processes temporal information remains elusive. According to previous work, time-keeping in medial premotor cortex (MPC) is governed by four kinds of ramp cell populations (Merchant et al., 2011). We believe that these cell populations participate in temporal information processing in MPC. Hence, in this the present study, we present a model that uses spiking neuron, including these cell populations, to construct a complete circuit for temporal processing. By combining the time-adaptive drift-diffusion model (TDDM) with the transmission of impulse information between neurons, this new model is able to successfully reproduce the result of synchronization-continuation tapping task (SCT). We also discovered that the neurons that we used exhibited some of the firing properties of time-related neurons detected by electrophysiological experiments in other studies. Therefore, we believe that our model reflects many of the physiological of neural circuits in the biological brain and can explain some of the phenomena in the temporal-perception process.

Objective: Larotaxel is a new chemical structure drug, which has not been marketed worldwide. Accordingly, the standard identification and quantification methods for larotaxel remain unclear. The spectrometric analyses were performed for verifying weight molecular formula, molecular weight and chemical structure of larotaxel. Besides, a quantification method was developed for measuring larotaxel in the liposomes., Methods: The molecular formula, molecular weight and chemical structure of larotaxel were studied by using mass spectrometry (MS), infra-red (IR), nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-vis) spectrometric techniques. The absorption wavelength of larotaxel was investigated by UV-vis spectrophotometry full-wavelength scanning. Besides, a quantification method was developed by high performance liquid chromatography (HPLC), and then validated by measuring the encapsulation efficacy of larotaxel liposomes., Results: The four spectral characteristics of larotaxel were revealed and the corresponding standard spectra were defined. It was confirmed that larotaxel had the structure of tricyclic diterpenoids, with the molecular formula of C45H53NO14, the molecular weight of 831.900 1, and the maximum absorption wavelength of 230 nm. The quantitative method of larotaxel was established by using HPLC with a reversed phase C18 column (5 μm, 250 mm×4.6 mm), a mobile phase of acetonitrile-water (75:25, volume/volume), and a detection wavelength of 230 nm. The validation study exhibited that the established HPLC method was stable, and had a high recovery and precision in the quantitative measurement of larotaxel in liposomes. In addition, a new kind of larotaxel liposomes was also successfully prepared. The particle size of the liposomes was about 105 nm, with an even size distribution. And the encapsulation efficiency of larotaxel in the liposomes was above 80%., Conclusion: The present study offers reference standard spectra of larotaxel, including MS, IR, NMR, and UV-vis, and confirms the molecular formula, molecular weight and chemical structure of larotaxel. Besides, the study develops a rapid HPLC method for quality control of larotaxel liposomes.