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This study aimed to investigate the mechanism of action of myrrh in breast cancer (BC) treatment and identify its effective constituents. Data on the compounds and targets of myrrh were collected from the TCMSP, PubChem, and Swiss Target Prediction databases. BC-related targets were obtained from the Genecard database. A protein-protein interaction (PPI) analysis, gene ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted on the intersecting targets of the disease and drug. The key targets of myrrh in BC treatment were identified based on the PPI network. The active constituents of myrrh were determined through reverse-screening using the top 20 KEGG pathways. Macromolecular docking studies, molecular dynamic (MD) simulations, and cell assays were utilized to validate the active constituents and critical targets. Network pharmacology indicated that VEGFA, TP53, ESR1, EGFR, and AKT1 are key targets of myrrh. Pelargonidin chloride, Quercetin, and Naringenin were identified as the active constituents of myrrh. Macromolecular docking showed that Quercetin and Naringenin have strong docking capabilities with ESR1. The results of MD simulation experiments align with those of molecular docking experiments. Cell and western blot assays demonstrated that Quercetin and Naringenin could inhibit MCF-7 cells and significantly reduce the expression of ESR1 protein. The findings reveal the active constituents, key targets, and molecular mechanisms of myrrh in BC treatment, providing scientific evidence that supports the role of myrrh in BC therapy. Furthermore, the results suggest that network pharmacology predictions require experimental validation for reliability., (© 2024 John Wiley & Sons Ltd.)

Background: This study investigated the effects of caffeinated chewing gum on fatigue index and 400-meter performance in trained sprinters., Methods: Nineteen participants (age: 20.9 ± 1.0 years; height: 175.6 ± 4.9 cm; mass: 66.5 ± 5.6 kg; training age: 7.9 ± 1.0 years) were randomly assigned to either a caffeine trial (CAF) or a placebo trial (PL) using a double-blind, randomized crossover design. The participants in the CAF trial chewed a gum containing 3 mg/kg of caffeine for a period of 10 minutes, while those in the PL trial chewed a gum containing a placebo with no caffeine. Following a 15-minute period of rest, the fatigue index was tested by six maximal 35-meter sprints with a 10-second rest between efforts. After this, at least 30 minutes of rest was permitted, during which time the participants engaged in brief warm-up activities prior to the commencement of the 400-meter sprint test. Saliva samples were collected before chewing gum, before the fatigue test and before 400-meters sprinting., Results: The fatigue index was significantly lower in the CAF trial compared to the PL trial (CAF: 8.1 ± 2.5%; PL: 9.6 ± 4.8%; p  = 0.046, Cohen's d = 039). The CAF trial demonstrated significantly lower sprint time for the 300-400 meter segment (CAF: 14.73 ± 1.35 seconds; PL: 15.23 ± 1.30 seconds; p  = 0.019, Cohen's d = 0.37) and total sprint time compared to the PL trial (CAF: 53.87 ± 2.88 seconds; PL: 54.68 ± 3.37 seconds; p  = 0.003, Cohen's d = 0.27). Saliva caffeine and α-amylase concentration were significantly higher in the CAF trial compared to the PL trial ( p  < 0.05)., Conclusion: The present study demonstrated that caffeine gum supplementation prior to exercise significantly reduced the fatigue index and increased the capacity to maintain speed, particularly in the final 300 to 400 meters, as well as enhancing 400-meter sprint performance.

Background and Purpose: Protein palmitoylation is involved in learning and memory, and in emotional disorders. Yet, the underlying mechanisms in these processes remain unclear. Herein, we describe that A-kinase anchoring protein 150 (AKAP150) is essential and sufficient for depressive-like behaviours in mice via a palmitoylation-dependent mechanism., Experimental Approach: Depressive-like behaviours in mice were induced by chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). Palmitoylated proteins in the basolateral amygdala (BLA) were assessed by an acyl-biotin exchange assay. Genetic and pharmacological approaches were used to investigate the role of the DHHC2-mediated AKAP150 palmitoylation signalling pathway in depressive-like behaviours. Electrophysiological recording, western blotting and co-immunoprecipitation were performed to define the mechanistic pathway., Key Results: Chronic stress successfully induced depressive-like behaviours in mice and enhanced AKAP150 palmitoylation in the BLA, and a palmitoylation inhibitor was enough to reverse these changes. Blocking the AKAP150-PKA interaction with the peptide Ht-31 abolished the CRS-induced AKAP150 palmitoylation signalling pathway. DHHC2 expression and palmitoylation levels were both increased after chronic stress. DHHC2 knockdown prevented CRS-induced depressive-like behaviours, as well as attenuating AKAP150 signalling and synaptic transmission in the BLA in CRS-treated mice., Conclusion and Implications: These results delineate that DHHC2 modulates chronic stress-induced depressive-like behaviours and synaptic transmission in the BLA via the AKAP150 palmitoylation signalling pathway, and this pathway may be considered as a promising novel therapeutic target for major depressive disorder., (© 2024 British Pharmacological Society.)

Background: Venous complications after pediatric liver transplantation seriously affect the survival rate of patients and grafts. At present, the diagnostic indicators have not been unified. Venous complications may cause portal hypertension, which may lead to splenomegaly and splenic vein dilatation. Therefore, the changes in spleen may be closely related to the venous complications. The purpose of this study was to explore the relationship between ultrasonic splenic parameters and venous complications and to study whether these splenic parameters can be used for the diagnosis of venous complications., Methods: We retrospectively included pediatric patients who underwent liver transplantation and collected ultrasonic spleen parameters before, and then 1-3 days, 1-3 weeks, 1-3 months, and 4-12 months after liver transplantation. We observed whether there were portal vein or hepatic vein complications within 1 year after liver transplantation., Results: Among 109 pediatric patients after liver transplantation included in our study, 11 of them suffered from portal vein complications and nine hepatic vein complications. Spleen transverse diameter, spleen longitudinal diameter, spleen portal vein diameter, spleen index, spleen transverse diameter ratio, spleen longitudinal diameter ratio, and spleen index ratio were independent risk factors of venous complications. The accuracy of spleen transverse diameter (AUROC: 0.73), spleen index (AUROC: 0.70), spleen transverse diameter ratio (AUROC: 0.71), and spleen index ratio (AUROC: 0.72) in predicting venous complications were higher than other ones., Conclusions: Ultrasonic examination is a common follow-up method for pediatric patients after liver transplantation and the application of ultrasonic spleen parameters may be helpful to monitor venous complications., (© 2024 Wiley Periodicals LLC.)

Protein posttranslational modification regulates synaptic protein stability, sorting and trafficking, and is involved in emotional disorders. Yet the molecular mechanisms regulating emotional disorders remain unelucidated. Here we report unknown roles of protein palmitoylation/nitrosylation crosstalk in regulating anxiety-like behaviors in rats. According to the percentages of open arm duration in the elevated plus maze test, the rats were divided into high-, intermediate- and low-anxiety groups. The palmitoylation and nitrosylation levels were detected by acyl-biotin exchange assay, and we found low palmitoylation and high nitrosylation levels in the basolateral amygdala (BLA) of high-anxiety rats. Furthermore, we observed that 2-bromopalmitate (2-BP), a palmitoylation inhibitor, induced anxiety-like behaviors, accompanied with decreased amplitude and frequency of mEPSCs and mIPSCs in the BLA. Additionally, we also found that inhibiting nNOS activity with 7-nitroindazole (7-NI) in the BLA caused anxiolytic effects and reduced the synaptic transmission. Interestingly, diazepam (DZP) rapidly elevated the protein palmitoylation level and attenuated the protein nitrosylation level in the BLA. Specifically, similar to DZP, the voluntary wheel running exerted DZP-like anxiolytic action, and induced high palmitoylation and low nitrosylation levels in the BLA. Lastly, blocking the protein palmitoylation with 2-BP induced an increase in protein nitrosylation level, and attenuating the nNOS activity by 7-NI elevated the protein palmitoylation level. Collectively, these results show a critical role of protein palmitoylation/nitrosylation crosstalk in orchestrating anxiety behavior in rats, and it may serve as a potential target for anxiolytic intervention., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background and Objectives: Parkinson's disease (PD) and chronic periodontitis (CP) are both inflammatory diseases; a correlation between the two diseases has been reported, but the underlying mechanisms of this association have not been investigated. We investigated the common molecular mechanisms between PD and CP and the role of immune cells in the pathogenesis of them using bioinformatics analyses to elucidate the association between the two diseases., Methods: We obtained gene expression data from the Gene Expression Omnibus (GEO) database: GSE10334, GSE16134, and GSE23586 for CP gingival samples and GSE20146 for PD brain samples. Subsequently, we conducted an enrichment analysis of the differentially expressed genes (DEGs) using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Moreover, all DEGs were analysed for protein-transcription factor interactions and protein-immune cell co-expression. We constructed protein-transcription factor, protein-protein interaction (PPI), and protein-immune cell co-expression networks using the Cytoscape software. Moreover, we identified the hub genes and investigated them for potential diagnostic value., Results and Conclusion: We identified 99 DEGs in the three CP datasets, 520 DEGs in the PD dataset and found five common DEGs in the CP and PD datasets, namely CXCR4, CXCL8, CD19, RPTN, and SLC16A9. These common DEGs identified in our study may have a potential impact on disease pathogenesis through the involvement of CXCR4-CXCL8-CD19 protein-complexes in dendritic cells. Therefore, CD19, LCP2, CXCR4, and LYN could be used as target molecules for the clinical diagnosis of both diseases., (© 2023 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Background: The clinical use of transthoracic echocardiography (TTE) in patients with acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) has dramatically increased, its impact on long-term prognosis in these patients has not been studied. This study aimed to explore the effect of early-TTE on long-term mortality in patients with moderate-to-severe ARDS in ICU., Methods: A total of 2833 patients with moderate-to-severe ARDS who had or had not received early-TTE were obtained from the Medical Information Mart for Intensive Care (MIMIC-III) database after imputing missing values by a random forest model, patients were divided into early-TTE group and non-early-TTE group according to whether they received TTE examination in ICU. A variety of statistical methods were used to balance 41 covariates and increase the reliability of this study, including propensity score matching, inverse probability of treatment weight, covariate balancing propensity score, multivariable regression, and doubly robust estimation. Chi-Square test and t-tests were used to examine the differences between groups for categorical and continuous data, respectively., Results: There was a significant improvement in 90-day mortality in the early-TTE group compared to non-early-TTE group (odds ratio  =  0.79, 95% CI: 0.64-0.98, p -value  =  0.036), revealing a beneficial effect of early-TTE. Net-input was significantly decreased in the early-TTE group on the third day of ICU admission and throughout the ICU stay, compared with non-early-TTE group (838.57 vs. 1181.89 mL, p -value  =  0.014; 4542.54 vs. 8025.25 mL, p -value  =  0.05). There was a significant difference in the reduction of serum lactate between the two groups, revealing the beneficial effect of early-TTE (0.59 vs. 0.83, p -value  =  0.009). Furthermore, the reduction in the proportion of acute kidney injury demonstrated a correlation between early-TTE and kidney protection (33% vs. 40%, p -value < 0.001)., Conclusions: Early application of TTE is beneficial to improve the long-term mortality of patients with moderate-to-severe ARDS., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The study aimed to establish a prognostic survival model with 8 pyroptosis-and-cuproptosis-related genes to examine the prognostic effect in patients of hepatocellular carcinoma (HCC)., Methods: We downloaded gene expression data and clinical information of HCC patients from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). The clustering analysis and cox regression with LASSO were used for constructing an 8 PCmRNAs survival model. Using TCGA, ICGC and GEO cohort, the overall survival (OS) between high- and low- risk group was determined. We also evaluated independent prognostic indicators using univariate and multivariate analyses. The relatively bioinformatics analysis, including immune cell infiltration, function enrichment and drug sensitivity analyses, was performed as well. The gene expression of 8 PCmRNAs in vitro were validated in several HCC cell lines by qRT-PCR and Western blot. The relationship between GZMA and Fludarabine were further checked by CCK-8 assay., Results: The survival prognostic model was constructed with ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NLRP6, NOD1 and GZMA using data from TCGA cohort. The ICGC and GEO cohort were used for model validation. Receiver operating characteristic (ROC) curves showed a good survival prediction by this model. Risk scores had the highest predictable value for survival among Stage, Age, Gender and Grade. Most Immune cells and immune functions were decreased in high-risk group. Besides, function enrichment analyses showed that steroid metabolic process, hormone metabolic process, collagen - containing extracellular matrix, oxidoreductase activity and pyruvate metabolism were enriched. Potential drugs targeted different PCDEGs like Nelarabine, Dexamethasone and Fludarabine were found as well. ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NOD1 were upregulated while NLRP6 and GZMA were downregulated in most HCC cell lines. The potential therapy of Fludarabine was demonstrated when GZMA was low expressed in Huh7 cell line., Conclusion: We constructed a novel 8-gene (ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NLRP6, NOD1 and GZMA) prognostic model and explored potential functional information and microenvironment of HCC, which might be worthy of clinical application. In addition, several potential chemotherapy drugs were screened and Fludarabine might be effective for HCC patients whose GZMA was low expressed., (© 2023. The Author(s).)

Background: Placement of a central venous catheter (CVC) is a common procedure for spinal surgery and is relatively safe under ultrasound guidance., Case Presentation: We report the case of a 56-year-old female who underwent ultrasound-guided placement of an internal jugular vein CVC for fluid replacement during spinal surgery for thoracic vertebral burst compression fracture and multiple rib fractures as a result of a high-altitude fall injury. Hemothorax developed intraoperatively. During a thoracotomy, the tip of the CVC was found within the chest cavity. The presence of chest trauma may impact on clinician's appreciation of the potential complications of internal jugular vein CVC placement., Conclusion: The present case demonstrates the need for clinical awareness of the potential complications of CVC placement in patients with chest trauma and the need for adequate training in this technique., (© 2023. The Author(s).)

Black spot disease (PBS) caused by Alternaria alternata is an economic disease of pear (Pyrus pyrifolia Nakai). Developing cultivars with durable PBS resistance traits is an important research objective for improving pear germplasm. The Deshengxiang is a popular pear variety in China and resistant to PBS. This study aimed to detect quantitative trait loci (QTL) associated with PBS resistance trait in pear and determine closely linked molecular markers by specific locus amplified fragment sequencing (SLAF-seq). F1 population resulting from a cross between "Deshengxiang" (female) and "Guiguan," a susceptible (male) variety, was developed and evaluated in 2016 and 2017. SLAF technology was used to discover SNPs in the F1 individuals and subsequently a high-density genetic linkage map for PBS resistance was constructed which contained 17,604 SNP markers. Based on the linkage map, the markers were distributed into 17 linkage groups, spanning 1548.48 cM, with a mean marker distance of 0.09 cM, representing the densest genetic map of the genus Pyrus. QTL analysis of PBS resistance identified a locus strongly related to PBS resistance at 77.68 ~ 112.99 cM on linkage group 15, which was further narrowed down to 93.79 ~ 112.99 cM. Two markers, Marker94293 and Marker94206, located at 97.47 and 102.93 cM, were closely associated with PBS resistance, with a Δ (SNP index) value of 0.46. Co-localization of QTL interval, bioinformatics analysis, and functional annotation revealed PBS putative candidate genes. Overall, the high-density pear linkage map is a suitable reference for mapping PBS resistance trait, QTL, and genes identified in this study contribute information that could be useful for PBS improvement in pear., (© 2022. The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences.)

Objective: To compare the rehabilitation effects of extracorporeal shock wave therapy (ESWT) and thermomagnetic therapy (TMT) in patients with low back pain (LBP)., Methods: As a single-centre retrospective observational study, clinical data of patients with LBP who received rehabilitation treatment in our hospital from January 2020 to May 2021 were retrospectively collected. Based on the treatment mode, the patients were retrospectively divided into two groups: the control group (patients received core muscle training + TMT, n=51) and the observation group (patients received core muscle training + ESWT, n=56). The general data of the patients were collected and the groups were matched for age, gender and pain duration. The visual analogue scale (VAS) score of pain, improvement of limb function, β-endorphin (β-EP), prostaglandin E2 (PGE2) and nitric oxide (NO) were compared between the two groups before and after treatment., Results: The VAS scores of the observation group were lower than those of the control group at one, two weeks and one month after the treatment ( P <0.05). After the treatment, the proportion of mild limb dysfunction in the observation group was 57.14% (32/56), which was higher than 35.29% (1 /51) in the control group. The proportion of patients with severe and obvious disorders was 0 and 5.36% (3/56), respectively, which was lower than 11.76% (6/51) and 5.88% (3/51) in the control group ( P <0.05). After the treatment, levels of NO and PGE2 in the observation group were lower, and the level of β-EP was significantly lower than in the control group ( P <0.05)., Conclusions: A combination of core muscle training and ESWT can effectively improve the analgesic effect of the treatment and promote greater improvement of limb function in patients with LBP., (Copyright: © Pakistan Journal of Medical Sciences.)

Objective: To investigate the effects of glucocorticoid receptor agonists on hyperalgesia in rats with neuropathic pain (NPP) by regulating nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/interleukin-1β (IL-1β) pathway and its mechanisms., Methods: Forty SD rats were divided into control group, NPP model group, NPP treated with NLRP3 inhibitor group and dexamethasone treatment group with 10 rats in each group. The NPP rat model was induced by vincristine. The model group was established according to the above method, the NLRP3 inhibitor group was treated with NLRP3 inhibitor (MCC950) after the NPP model was established, and the treatment group was treated with glucocorticoid receptor agonist (dexamethasone) after the model was established according to the design. The rats of the control group were given the same amount of normal saline. After 7 days of intervention, the mechanical pain threshold, thermal pain threshold, morphological changes of spinal dorsal horn, pain factors (prostaglandin E2 (PGE2), substance P (SP), 5-hydroxytryptamine (5-HT)), inflammatory factors (interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6)), and NLRP3/IL-1β protein expressions were determined and compared among the four groups., Results: Compared with the model group, the pathological changes of spinal dorsal horn neurons in NLRP3 inhibitor group and treatment group were alleviated significantly, the arrangement of neurons was tended to be close, the number of neurons was gradually returned to normal, and the pyknosis of neurons was decreased. Compared with the control group, the mechanical pain threshold and thermal pain threshold of the model group were decreased significantly ( P ＜0.05), and the expressions of inflammatory factors, pain factors and NLRP3, IL-1β protein were increased significantly ( P ＜0.05); compared with the model group, the mechanical pain threshold and thermal pain threshold of the NLRP3 inhibitor group and the dexamethasone treatment group were increased significantly ( P ＜0.05), and the expressions of inflammatory factors, pain factors and NLRP3, IL-1β protein were decreased significantly ( P ＜ 0.05). The difference between NLRP3 inhibitor group and treatment group was not statistically significant ( P ＞0.05)., Conclusion: Glucocorticoid receptor agonists may reduce the hyperalgesia of neuropathic pain rat model by down regulating NLRP3/IL-1β pathway, which may be the mechanism of dexamethasone on antiinflammatory of analgesia in early stage of NPP.

Objective: To investigate the case of a child infected with coronavirus disease 2019 (COVID-19) who had subsequent viral reactivation., Methods: We retrospectively analyzed the clinical manifestations, epidemiological data, laboratory and imaging examinations, treatment, and follow-up of the child. And then, we searched related literature using PubMed., Results: The 9-year-old boy was exposed to COVID-19 in Malawi and tested positive for NAT in Haikou, China. He was asymptomatic and admitted to our hospital. After six negative NATs, he was discharged from the hospital and quarantined in a hotel. His infection was reactivated again after 22 days (interval between first and last positive NATs). The cycle threshold (Ct) values of positive tests were 25 and 31, and the gene sequencing viral loads were very low. The viral strain Kenya/P2601/2020, a variant of the hCoV-19/Wuhan/IVDC-HB-01/2019 genome (GISAID accession IL: EPI&#95;ISL&#95;402119), was found when polymerase chain reaction enrichment was used to sequence the virus. However, people around him tested negative for COVID-19., Conclusion: First, we confirmed the reactivation of COVID-19 in a child. The risk of recurrent infection with SARS-CoV-2 was low, and the policy of strictly isolating patients carrying long-term viral ribonucleic acid should be reconsidered. The interval positivity was most likely due to incorrect sampling and/or testing methods. SGS and aB testing are recommended for children with viral reactivation. Second, SARS-CoV-2 viral reactivation cannot be ruled out. The possible mechanisms, such as prolonged infection and viral latent reactivation, need further investigation., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest., (© The Author(s) 2022.)

For many decades, several classical formulas on carbon equivalent (CE) have been widely used for evaluating the weldability of steels. Unfortunately, a single CE is impossible for various types of steels. In this study, the resistance spot weldability of medium-Mn steels was investigated. In particular, the influences of paint baking processes at different temperatures on the mechanical properties, fracture mode, and microstructure of weldment were studied. It was found that the paint baking above 170°C can change the tensile-shear failure of weldment from the undesired interfacial failure to the desired pull-out one, because the shrinkage of weldment during welding was compensated by the thermal expansion during the baking, leading to the "cold welding" realized for solid joining. Furthermore, a shrinkage-based criterion (∆ l ) was established for evaluating the weldability of greater range of alloyed steels more accurately and robustly than CE. The proposed criterion on measuring the weldability of high alloyed steels opens a promising path forward for designing a new generation of advanced high strength steels requiring good weldability., (© The Author(s) 2022. Published by Oxford University Press on behalf of the National Academy of Sciences.)

Background: Acute respiratory distress syndrome (ARDS) is a rapidly progressive and fatal respiratory failure disease that often occurs in critically ill patients. Since ARDS is associated with immune dysregulation and coagulation abnormalities, it is necessary to identify an appropriate predictor that can accurately predict ARDS mortality based on its pathophysiology. Therefore, this study aimed to evaluate the clinical value of neutrophils to lymphocytes and platelets ratio (N/LPR) in predicting 28-day mortality in ARDS patients., Methods: From July 2018 to October 2021, the medical records of ARDS patients were retrospective reviewed. Neutrophil count, lymphocyte count, and platelet count were collected, and the neutrophil-to-lymphocyte ratio (NLR) and N/LPR were calculated. Multivariate logistic regression analyses were performed to identify independent predictors of 28-day mortality in ARDS. Receiver operating characteristic (ROC) curve with the area under curve (AUC) was used to evaluate optimal cut-off values for 28-day mortality in ARDS. Kaplan-Meier analysis was used to estimate the 28-day survival probabilities stratified by optimal cut-off values of N/LPR and NLR., Results: A total of 136 ARDS patients were included in this study and were further divided into survivors (n = 69) and non-survivors (n = 67) groups according to their survival status on day 28. There were no significant differences between the two groups in age, sex, history of smoking and drinking, comorbidities, and reasons of admission (P > 0.05). Non-survivors had significantly higher neutrophil counts, NLR and N/LPR and had significantly lower platelet counts than survivors (P < 0.05). Multivariate regression analysis revealed that N/LPR, NLR and platelet counts were independent predictors for 28-day mortality in ARDS (P < 0.05). The ROC analyses showed that N/LPR with optimal cut-off value of 10.57 (sensitivity: 74.6%; specificity: 72.5%) is a more reliable predictor for 28-day mortality in ARDS than NLR and platelet count (AUC: 0.785 vs. 0.679 vs. 0.326). Further subgroup analysis confirmed that ARDS patients with N/LPR < 10.57 had significantly lower 28-day mortality than patients with N/LPR ≥ 10.57 (P < 0.001). Kaplan-Meier analysis also confirmed that ARDS patients with N/LPR < 10.57 had significantly longer survival., Conclusion: N/LPR is an independent risk factor associated with 28-day mortality in ARDS patients and shows better performance in predicting mortality rate than NLR., (© 2022. The Author(s).)

Background: Adjacent vertebral fracture (AVF) seemed to be a frequent and severe complication in osteoporotic vertebral compression fracture (OVCF) patients receiving percutaneous vertebroplasty  or percutaneous kyphoplasty (PKP), resulting in poor long-term outcome and recurrence of pain-related symptoms. Nonetheless, its mechanism remains unclear., Objectives: To investigate the potential predictor of AVF after PKP and figure out whether the intervertebral disc plays a role during the process of AVF., Study Design: Retrospective study., Setting: Department of Orthopedic, an affiliated hospital of a medical university., Methods: Clinical data of OVCF patients receiving PKP were reviewed in our hospital from January 2016 to December 2020. Four hundred and forty-five patients were recruited who met the abovementioned criteria in this study. The clinical data, including age, gender, bone mineral density (BMD), vertebral height, vertebral kyphosis angle, cement volume, cement distribution, as well as adjacent disc degeneration extent, were recorded for each patient. Independent-sample t tests and chi-squared tests were performed to compare these indexes. Bivariate correlation tests and multiple linear regression analyses were performed among potential predictors. Receiver operator characteristic (ROC) analysis and Kaplan-Meier plotter were applied to evaluate the diagnostic efficiency of parameters for predicting the occurrence of AVF., Results: Patients in both groups gained obvious improvements in symptomatic and radiographic indexes after first PKP. Statistically significant difference (P < 0.05) was only found between 2 groups with respect to BMD, kyphosis angle at last follow-up before second PKP, cement distribution, and disc degeneration grade. The ROC analysis showed that BMD = 15.5° was highly predictive of AVF after PKP (sensitivity, 92.2%; specificity, 24.6%; area under curve, 0.569, P = 0.109). Statistically significant difference of AVF incidence amongst patients with different cement distribution (P = 0.018) and similar trend was also found amongst patients with different disc degeneration (P = 0.000). Statistically significant difference was noted in terms of disc degeneration grade between 2 adjacent discs in AVF group., Limitations: The main limitation is the retrospective nature of this study., Conclusions: The risk of AVF should be focused, especially when OVCF patients with the following predictors: (1) BMD < -3.45; (2) kyphosis angle at last follow-up > 15.5°; (3) I or II cement distribution; and (4) IV or V disc degeneration. More prophylactic treatment should be prescribed for these patients to avoid the occurrence of AVF.

Purpose: Low calf circumference is an important indicator of malnutrition and has been widely studied, especially among older adults. However, data on the association between low calf circumference and mortality have been inconsistent. This systematic review was aimed to quantify this association., Methods: The internet databases (PubMed, Embase, ScienceDirect and Cochrane Library databases) were systematically searched from inception to November 01, 2021 for studies investigating the association between low calf circumference and mortality. A random effects model was adopted to pool the relevant data., Results: Low calf circumference was associated with a higher risk of mortality than normal calf circumference, with a pooled HR of 2.42 (95% CI 1.97-2.97, I 2  = 74.3%). In addition, this association between low calf circumference and morality was still statistically significant in the subgroup analysis across different settings, including hospitals (pooled HR = 2.63, 95% CI 1.93-3.58), nursing homes (pooled HR = 2.49, 95% CI 1.76-3.54), and communities (pooled HR = 2.22, 95% CI 1.60-3.07). Other subgroup analyses based on different cutoffs of calf circumference showed that, compared to individual with normal calf circumference, participants with low calf circumference had an increased risk of mortality (pooled HR = 2.66, 95% CI 2.06-3.43) when using the Asian Working Group for Sarcopenia (AWGS) criterion (≤ 34 cm for males and ≤ 33 cm for females). Similar results were found when the Mini Nutritional Assessment (MNA) criterion (≤ 31 cm) was used, with a pooled HR of 2.11 (95% CI 1.59-2.81)., Conclusion: Calf circumference, which is simple and convenient to measure, could be used to stratify the high-risk group, as low calf circumference was significantly associated with mortality among patients. Interventions, including exercise and nutrition programs, could be conducted promptly once low calf circumference is detected., (© 2022. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

The number of smoking patients receiving anesthesia and surgical treatment is increasing day by day. It will be useful for medical advancement to explore whether smoking is an independent risk factor for postoperative cognitive impairment. A double-blind, parallel, and controlled study was conducted on 112 patients who fulfilled the criteria for inclusion in this study and planned to undergo painless gastroscopy under general anesthesia. The baseline mini-mental state examination (MMSE) scores and basic information were collected. The changes in the MMSE scores after waking up and 3 days after anesthesia were observed, and the adverse events (respiratory adverse reactions, circulatory fluctuations, and adverse reactions, drug use, etc.) were analyzed by logistic regression. The baseline level of each group is consistent, which is worth studying. The MMSE score of the smoking group after anesthesia was significantly different from that of the control group ( p  < 0.05), but there was no significant difference between the two groups 3 days after anesthesia. Among them, the differences in adverse events between the two groups were in terms of hiccup, postoperative cough, and SpO 2  < 90% ( p  < 0.05). Regression analysis indicates that smoking after anesthesia leads to the occurrence of postoperative cough. Smoking is probably an independent risk factor for post-operative cognitive dysfunction (POCD) in early postoperative patients., Competing Interests: Zhao‐Qiong Zhu and Yu‐Hang Zhu are reviewers for Ibrain but are not involved in the peer review process of this manuscript. Other authors declare no conflict of interest., (© 2022 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University and Wiley‐VCH GmbH.)

To conduct an anti-tumor research by using targeted drug-loaded cell-derived microparticles to target the tumor microenvironment and enhance NK cell killing function. In this experiment, we obtained HepG2 tumor cell-derived microparticles by physical extrusion, high speed centrifugation and filtration, modified the hepatocellular carcinoma targeting peptide SP94 on the surface of microparticles and encapsulated the TGF- β inhibitor SB505124. Finally we validated and analyzed whether the new drug delivery system can target to tumor site and enhance the anti-tumor function of NK cells. This type of novel targeted cell-derived microparticles drug delivery system will provide a novel idea for tumor immunotherapy.

Background: Bone marrow mesenchymal stem cells have always been a heated research topic in bone tissue regeneration and repair because of their self-renewal and multi-differentiation potential. A large number of studies have been focused on finding the inducing factors that will promote the osteogenic differentiation of bone marrow mesenchymal stem cells. Previous studies have shown that macrophage exosomes or miRNA-26a-5p can make it work, but the function of this kind of substance on cell osteogenic differentiation has not been public., Methods: M2 macrophages are obtained from IL-4 polarized bone marrow-derived macrophages. Exosomes were isolated from the supernatant of M2 macrophages and identified via transmission electron microscopy (TEM), western blotting, and DLS. Chondrogenic differentiation potential was detected by Alcian blue staining. Oil red O staining was used to detect the potential for lipogenic differentiation. And MTT would detect the proliferative capacity of cells. Western blot was performed to detect differential expression of osteogenic differentiation-related proteins., Results: The results showed that M2 macrophage exosomes will promote bone differentiation and at the same time inhibit lipid differentiation. In addition, M2 macrophage-derived exosomes have the function of promoting the expression of SOX and Aggrecan suppressing the level of MMP13. The exosome inhibitor GW4689 suppresses miRNA-26a-5p in M2 macrophage exosomes, and the treated exosomes do not play an important role in promoting bone differentiation. Moreover, miRNA-26a-5p can enable to promote bone differentiation and inhibit lipid differentiation. miRNA-26a-5p can promote the expression of ALP (alkaline phosphatase), RUNX-2 (Runt-related transcription factor 2), OPN(osteopontin), and Col-2(collagen type II). Therefore, it is speculated that exosomal miRNA-26a-5p is indispensable in osteogenic differentiation., Conclusions: The present study indicated that M2 macrophage exosomes carrying miRNA-26a-5p can induce osteogenic differentiation of bone marrow-derived stem cells to inhibit lipogenic differentiation, and miRNA-26a-5p will also promote the expression of osteogenic differentiation-related proteins ALP, RUNX-2, OPN, and Col-2., (© 2022. The Author(s).)

Background and Objective: Prostate cancer (PCa) is one of the most common malignant tumors in men. Geriatric Nutritional Risk Index (GNRI) is an objective index for evaluating nutritional status of elderly people over 65 years old. The aim of the current study was to explore the correlation and predictive value between GNRI and postoperative recovery and complications in PCa patients undergoing laparoscopic radical prostatectomy (LRP)., Methods: Taking 98 as the GNRI boundary value, 96 PCa patients (aged≥65 y) undergoing LRP in the Department of Urology, Affiliated Hospital of North Sichuan Medical College from January 2018 to December 2020 were grouped into malnutrition group (MNg, 34 patients, 35.4%) and normal nutrition group (NNg, 62 patients, 64.6%). Basic information, laboratory examination indexes, operation conditions, postoperative complications and postoperative recovery indexes of patients were recorded and retrospectively analyzed. Clavien-Dindo Classification System (CDCS) was used to assess postoperative complications. T-test was used to analyze differences between the two groups. ROC curve was generated to determine the predictive value of GNRI for postoperative complications., Results: Percentage of complications was significantly higher in MNg group compared with that in NNg group (P < 0.01). The average grade based on CDCS was significantly lower in NNg group compared with that in MNg group (P < 0.01). Body weight, Body Mass Index (BMI), preoperative hemoglobin value (HGB), serum albumin (ALB) values of MNg and NNg were significantly positively correlated with GNRI (P<0.01). Incidence and severity of postoperative complications of MNg patients were significantly higher compared with those of NNg patients (P<0.05). Average hospitalization cost of MNg patients was higher in MNg patients compared with that of NNg patients (P<0.05). Duration of post-anesthesia care unit (PACU), duration of antibiotic use and duration of indwelling drainage tube were longer in MNg patients compared with those in NNg patients (P<0.05). Furthermore, volume of indwelling drainage tube was higher in MNg patients compared with that in NNg patients (P<0.05)., Conclusion: GNRI is an effective and reliable tool for evaluation of preoperative nutritional status of prostate cancer patients. The findings showed that GNRI is correlated with postoperative recovery and complications, and is an effective predictive marker., Competing Interests: The authors have declared that no competing interests exist.

Although 1,10-phenanthroline-based ligands have recently shown vast opportunities for the separation of trivalent actinides (Ans(III)) from lanthanides (Lns(III)), the optimization and design of the extractant structure based on the phenanthroline framework remain hotspots for further improving the separation. Following the strategy of hard and soft donor atom combination, for the first time, the quinoline group was attached to the 1,10-phenanthroline skeleton, giving a lipophilic ligand, 2,9-diacyl-bis((3,4-dihydroquinoline-1((2H)-yl)-1),10-phenanthroline (QL-DAPhen)), for Am(III)/Eu(III) separation. In the presence of sodium nitrate, the ligand can effectively extract Am(III) over Eu(III) in HNO 3 solution, with the separation factor ( SF Am/Eu ) ranging from 29 to 44. The coordination chemistry of Eu(III) with QL-DAPhen was investigated by slope analysis, NMR titration, UV-vis titration, Fourier transform infrared spectroscopy, electrospray ionization-mass spectrometry, and theoretical calculations. The experimental results unanimously confirm that the ligand forms both 1:1 and 1:2 complexes with Eu(III), and the stability constants (log β ) of each of the two complexes were obtained. Density functional theory calculations show that the Am-N bonds have more covalent characteristics than the Eu-N bonds in the complexes, which reveals the reason why the ligand preferentially bonds with Am(III). Meanwhile, the thermodynamic analysis reveals that the 1:1 complex is more thermodynamically stable than the 1:2 complex. The findings of this work have laid a solid theoretical foundation for the application of phenanthroline-based ligands in the separation of An(III) from practical systems.

Background: A few reports have shown that unilateral transverse process-pedicle percutaneous kyphoplasty is a good choice for patients with osteoporotic vertebral compression fracture (OVCF). However, this issue remains controversial and the related comprehensive research was lacked., Methods: A retrospective study was conducted on patients receiving PKP surgery for OVCF. Patients were divided into three groups according to surgical approach. Symptom and radiographical evaluation were performed preoperatively, 1-month postoperatively, 1-year postoperatively and follow-ups. And follow-ups were repeated every year. Visual Analogue Scale Score (VAS), Oswestry Disability Index (ODI) scores, anterior vertebral height, coronal Cobb angle and sagittal Cobb angle was determined and compared among three groups., Results: Totally 447 patients were included with an average age of 76.6 ± 7.2 years old. UTP showed significantly shorter surgical duration (p < 0.001), lower cement volume (p < 0.001) but higher cement leakage proportion (p = 0.044). No significant statistical difference was found in terms of improvement rates among three groups. Besides, it was notable that the a significantly higher coronal Cobb angle was observed in UTP group, and a about 4°coronal correction was found after UTP PKP., Conclusion: UTTP PKP could achieve similar symptoms relief and kyphosis correction as UTP and BTP PKP. However, it had shorter surgical time and less radio exposure than BTP PKP, lower risk of cement leakage and higher proportion of bilaterally cement distribution than UTP PKP. It seemed to be a better choice for patients with OVCF. In addition, we found that UTP PKP was especially fit for OVCF patients with asymmetrical vertebral compression.

The design and development of a water-soluble heterocyclic ligand are believed to be an alternative way for improving the separation efficiency of actinides from lanthanides. Herein, we designed and synthesized a novel hydrophilic multidentate ligand: disulfonated N , N '-diphenyl-2,9-diamide-1,10-phenanthroline (DS-Ph-DAPhen) with soft and hard donor atoms, as a masking agent in aqueous solutions for Am(III) separation. The combination of N , N , N ', N '-tetraoctyldiglycolamide in kerosene and DS-Ph-DAPhen in aqueous phases could separate Am(III) from Eu(III) across a range of nitric acid concentrations with very high selectivity. The coordination behaviors of Eu(III) with DS-Ph-DAPhen in aqueous solutions were studied by UV-vis titration, electrospray ionization mass spectrometry, and Fourier transform infrared spectra. The results indicated that Eu(III) ions could form both 1:1 and 1:2 complexes with the DS-Ph-DAPhen ligand in aqueous solution. Density functional theory calculation suggests that there are more covalent characters for Am-N bonds than that for Eu-N bonds in the complexes, which supports the better selectivity of the DS-Ph-DAPhen ligand toward Am(III) over Eu(III). This work demonstrates a feasible alternative approach to separating trivalent actinides from lanthanides with high selectivity.

Background: We have performed the direct and network meta-analysis to evaluate the safety and efficacy of robot-assisted (RARC) versus laparoscopic (LRC) versus open radical cystectomy (ORC) for bladder cancer (BCa)., Methods: A systematic search of PubMed, Cochrane Library, and Embase was performed up until Dec 20, 2019. Outcome indexes include oncologic outcomes (the recurrence rate, mortality), pathologic outcomes (lymph node yield (LNY), positive lymph node (PLN), positive surgical margins (PSM)), perioperative outcomes (operating time (OP), estimated blood loss (EBL), blood transfusion rate, the length of hospital stay (LOS) and the time to regular diet) and postoperative 90-day complications., Results: We have analyzed 6 RCTs, 23 prospective studies, and 25 retrospective studies (54 articles: 6382 patients). On one hand, the direct meta-analysis shows RARC is better than LRC or ORC. On the other hand, the clinical effects of the recurrence rate, Morbidity, PSM, LNY, PLN, and postoperative 90-day complications of RARC, LRC and ORC are all no statistical significance by network meta-analysis. Moreover, the probability rank shows that the comprehensive rank of RARC is better than LRC or ORC. The clinical effects of OP, EBL, LOS, blood transfusion rate and the time to regular diet are all statistical significance by network meta-analysis. There are ORC > LRC > RARC in the EBL ranking. Patients with RARC exhibited a decrease of LOS compared to those with LRC or ORC. Patients with RARC exhibited a decrease in blood transfusion rate and the time to regular diet compared to those with ORC. Patients with ORC exhibited an increase of OP compared to those with RARC or LRC. The heterogeneity tests of most studies are < 50%. Most studies have no publication bias and the quality of the selected studies is good., Conclusion: The direct meta-analysis and network meta-analysis suggest that RARC is better than LRC or ORC according to comprehensive analysis. However, we need a large sample size and more high-quality studies to verify and improve in the further., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ginkgetin, the extract of Ginkgo biloba leaves, has been reported to exert preventive and therapeutic effects on cardiovascular disease. However, little is known about its role in myocardial ischemia-reperfusion injury (MIRI). The present study aimed to unveil the function of ginkgetin in cardiomyocytes subjected to hypoxia/reoxygenation (H/R) injury. Cell Counting Kit-8 (CCK-8) was employed to evaluate the impact of ginkgetin on cell viability in the absence or presence of H/R. Proinflammatory cytokines and malondialdehyde (MDA), reactive oxygen species (SOD), and lactate dehydrogenase (LDH) were determined via corresponding kits. In addition, flow cytometry was performed to detect apoptotic level. Western blot analysis was utilized to estimate caspase-3 and cytochrome C. Ginkgetin had no significant effect on cell viability; however, it could enhance viability of H9C2 cells exposed to H/R. Inflammation and oxidative stress induced by H/R injury were relieved via pretreatment with ginkgetin. Preconditioning of ginkgetin also decreased apoptotic rate and the protein levels of caspase-3, cytochrome C under H/R condition. Furthermore, 2-HBA, an inducer of caspase-3, was used for the activation of caspase-3 signaling pathway. It was found that induction of caspase-3 eliminated the protective effect of ginkgetin on H9C2 cells exposed to H/R. These results indicated that ginkgetin attenuated inflammation, oxidative stress, and apoptosis. These protective roles of ginkgetin may attribute to caspase-3 dependent pathway., Competing Interests: The authors declare no competing interests., (Copyright © 2020 Xin Liu et al.)

Diglycolamide-based ligands have recently received increased attention due to their outstanding affinity for trivalent actinides and lanthanides. The structure optimization of the ligands, however, still remains a hot topic to achieve better extraction performance. In this work, we prepare and investigate three multidentate diglycolamide ligands for the selective separation of Eu(III) over Am(III) from a nitric acid solution to explore the effect on the extraction of alkyl groups on the nitrogen atoms in the center of the BisDGA ligands. The introduction of ethyl or isopropyl groups on the central nitrogen atoms greatly increased the distribution ratios of trivalent metal ions and enhanced the separation factor of Eu(III) over Am(III). The complexation behaviors of Eu(III) and Am(III) ions were studied by slope analyses, electrospray ionization mass spectrometry (ESI-MS), and extended X-ray absorption fine structure (EXAFS) spectroscopy. The results indicated that the trivalent metal ions were extracted as 1:2 and 1:3 complexes for all three BisDGA ligands during the extraction. Density functional theory (DFT) calculations verified the relevant experimental conclusion that the selectivity of THEE-BisDGA for Eu(III) is better than that for Am(III). The metal-DGA bonds in the ML 3 (NO 3 ) 3 complexes seem to be stronger than those in ML 2 (NO 3 ) 3 complexes.

BACKGROUND The present study was performed to assess the effect of mechanical stretch on the proliferation and contractile function of hBSMCs. MATERIAL AND METHODS hBSMCs and ICCs were seeded at 8×104 cells/well in 6-well silicone elastomer-bottomed culture plates coated with type I collagen, and grown to 80% confluence in DMEM/10% FBS and a 5% CO₂ humidified atmosphere at 37°C. Cells of hBSMCs and hBSMCs/ICCs of co-culture were then subjected to continuous cycles of stretch-relaxation using a computer-driven, stretch-inducing device. The treated concentration of imatinib was 10 μM. Mechanisms underlying observed hBSMCs contraction were examined using Western blotting and RT-PCR. The 0.1 μM carbachol was separately added to the experimental groups, and 300 s was recorded by laser scanning confocal microscope. RESULTS We found that mechanical stretch increased contraction and proliferation of hBSMCs. Calcium ion activity increased significantly after mechanical stretch. The number of hBSMCs was significantly increased after the combination mechanical stretch with ICCs treatment. After combination mechanical stretch with hBSMCs/ICCs treatment, the mRNA and protein level of M2, M3, and c-kit were significantly increased. After combination of mechanical stretch with no imatinib treatment, the proliferation of hBSMCs was higher than others, and the mRNA and protein level of M2 and M3 were significantly increased. CONCLUSIONS We revealed that ICCs could promote hBSMC proliferation and contraction, and cyclic stretch could promote acetylcholine receptor M2 and M3 caused by c-kit in the ICCs, which promoted the contraction of hBSMCs.

We present a physically-based approach for simulating makeup in face images. The key idea is to decompose the face image into intrinsic image layers - namely albedo, diffuse shading, and specular highlights - which are each differently affected by cosmetics, and then manipulate each layer according to corresponding models of reflectance. Accurate intrinsic image decompositions for faces are obtained with the help of human face priors, including statistics on skin reflectance and facial geometry. The intrinsic image layers are then transformed in appearance according to measured optical properties of cosmetics and proposed adaptations of physically-based reflectance models. With this approach, realistic results are generated in a manner that preserves the personal appearance features and lighting conditions of the target face while not requiring detailed geometric and reflectance measurements. We demonstrate this technique on various forms of cosmetics including foundation, blush, lipstick, and eye shadow. Results on both images and videos exhibit a close approximation to ground truth and compare favorably to existing techniques.

Purpose: To conduct a comprehensive meta-analysis of existing evidence to quantify and compare the safety and efficacy of PCNL, RIRS and ESWL for lower pole renal stones 10-20mm., Materials and Methods: We conducted a systematic literature search in the EMBASE, MEDLINE, Cochrane databases and Google Scholar to identify relevant studies published in English up to May 2018. Literature reviewed included meta-analyses, and randomized and nonrandomized studies. The subject in the management of PCNL, RIRS and ESWL of studies being patients who had lower pole renal stones 10-20mm were selected. The odd ratio (OR) and mean difference(MD) with its 95% confidence interval (CI) using fixed-or-random-model were calculated to estimate the safety and efficacy of PCNL, RIRS and ESWL for lower pole renal stones 10-20mm. Two reviewers independently assessed the quality of all included studies, and the RevMan 5.3 software was used to analyze the included studies., Results: Three randomized controlled trials and five retrospective case control studies were included, involving a total of 1615 patients in our meta-analysis. Our results suggest that, for lower pole renal stones 10-20mm, PCNL has a great advantage to RIRS(OR=1.95?95% CI?1.22-3.12?P =.005?I2 = 39%)  and ESWL(OR=0.22?95% CI?0.15-0.34?P <.00001?I2 = 0%) in stone-free rate. Comparing PCNL(MD=-24.97?95% CI?-40.90--9.04?P=.002; I2 = 76%) (MD=-2.43?95% CI:-4.70--0.17?P=.04?I2 = 99%) and RIRS(MD=-15.39?95% CI?-25.54--5.25?P=.003? I2 = 99%) (MD=-0.95?95% CI: -1.29--0.61? P<.00001? I2 = 96%), ESWL owns some advantages in shorter operative time and hospital stay. Both of PCNL (OR=70.21,95%CI:25.01-197.11,P<.00001) (OR=4.01,95%CI:2.04-7.89, P<.0001) and RIRS (OR=32.31,95%CI:18.39-56.76,P<.00001?I2=0%) (OR=3.06, 95%CI:1.94-4.84,P<.00001?I2=19%) have some strong points in lower retreatment rate and auxiliary procedure rate comparing ESWL, but no statistical significant difference is found between them(OR=0.46,95% CI:0.15-1.42,P =.18?I2=0%)(OR=0.75,95% CI:0.35-1.59,P =.45). About complication rate, there's no statistical significant difference found in PCNL(OR=1.42, 95%CI:0.91-2.21,P=.12?I2=0%), RIRS (OR=0.74,95%CI:0.51-1.07,P=.11?I2=30%) and ESWL(OR=0.41,95% CI:0.16-1.09,P=.07,I2=70%)., Conclusion: Both of PCNL and RIRS offer a longer operative time, the lower retreatment rate and auxiliary procedure rate while PCNL has the longest hospital stay and the highest SFR. However, ESWL is confirmed to have the lowest SFR, the higher retreatment rate and auxiliary procedure rate, but a shorter operative time and the shortest hospital stay. The overall complication rates among the three therapies are comparable.

Background: We assessed the Th17 (T-helper cell)/Treg (Regulatory T cell) imbalance in sepsis patients with multiple organ dysfunction syndrome (MODS) and the clinical benefits of continuous high-volume hemofiltration (HVHF)., Methods: 48 sepsis patients, including 22 patients with MODS (MODS group, n = 22) and 26 without (non-MODS group, n = 26), and 20 healthy volunteer controls were enrolled. The patients in MODS group were randomly divided into the continuous blood purification (CBP) group (n = 11) receiving conventional comprehensive treatment plus high-volume hemofiltration and the non-CBP group (n = 11) receiving conventional comprehensive treatment only. At day 28, all 48 patients were divided into the survival group (n = 36) and the non-survival group (n = 12). Venous blood samples, collected at 0, 6, 12 and 24 hours during hemofiltration (or equivalent times in the non-CBP group), were assessed by flow cytometry to detect the Th17 and Treg cells in peripheral blood. Serum cytokines (such as IL-6, IL-17, IL-23, IL-10 and TGF-β1) were detected by enzyme-linked immune sorbent assay (ELISA)., Results: Th17%, Treg%, Th17/Treg, IL-6, IL-17, IL-23, IL-10 and TGF-β1 were significantly higher in MODS and non-MODS group than in the health control (p<0.05), while Th17%, Treg%, Th17/Treg and measured cytokines were significantly higher in the MODS group compared to the non-MODS group (p<0.05). After HVHF treatment, Th17%, Treg%, Th17/Treg, IL-6, IL-17, and IL-10 were significantly reduced (p<0.05), while there were no significant changes in the non-CBP group (p>0.05). In addition, APACHE II and SOFA scores decreased markedly after HVHF treatment. Baseline Th17%, Treg%, Th17/Treg, IL-6, IL-17, IL-23, IL-10 and TGF-β1 were significantly higher in the non-survival group compared to the survival group. Both Th17% and Th17/Treg were positivity correlated with concentration of IL-6 and APACHE II score (p<0.01)., Conclusions: The level of Th17/Treg imbalance in sepsis is related to the occurrence and prognosis of MODS. High-volume hemofiltration can attenuate the Th17/Treg imbalance in sepsis patients, possibly by removing inflammatory mediators.

Aim: To determine the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE) for the non-invasive assessment of liver fibrosis in patients with autoimmune liver diseases (AILD) using liver biopsy as the reference standard., Methods: Patients with AILD who underwent liver biopsy and 2D-SWE were consecutively enrolled. Receiver operating characteristic (ROC) curves were constructed to assess the overall accuracy and to identify optimal cut-off values., Results: The characteristics of the diagnostic performance were determined for 114 patients with AILD. The areas under the ROC curves for significant fibrosis, severe fibrosis, and cirrhosis were 0.85, 0.85, and 0.86, respectively, and the optimal cut-off values associated with significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4) were 9.7 kPa, 13.2 kPa and 16.3 kPa, respectively. 2D-SWE showed sensitivity values of 81.7% for significant fibrosis, 83.0% for severe fibrosis, and 87.0% for cirrhosis, and the respective specificity values were 81.3%, 74.6%, and 80.2%. The overall concordance rate of the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages was 53.5%., Conclusion: 2D-SWE showed promising diagnostic performance for assessing liver fibrosis stages and exhibited high cut-off values in patients with AILD. Low overall concordance rate was observed in the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages., Competing Interests: Conflict-of-interest statement: The authors declare no financial conflict of interest.

Objective: To assess the benefit of intra-articular injection of Botulinum toxin A (BoNT-A) for chronic refractory joint pain regardless of joint or pathology., Data Sources: The search was performed on Ovid MEDLINE(R) In-Process and Other Non-Indexed Citations, Ovid MEDLINE(R), Ovid EMBASE, Web of Science, and Scopus inception through Week 12, 2016. Trial selection: Clinical randomized controlled trials that evaluated BoNT-A intra-articular injection in patients with refractory joint pain were included., Data Extraction: Two independent reviewers conducted data extraction., Results: A total of 6 out of 284 records were included. The analysis indicated that a statistically significant decreased pain score was found in BoNT-A therapy group than control group with WMD=1.10 (95% CI: 0.35 to 1.85; P<0.001; I 2 =95%); WMD=0.7 (95% CI: 0.09 to 1.32; P=0.02; I 2 =0%) at week 4, and 8 after injection, respectively. WOMAC score was also significant decreased in BoNT-A therapy group than control group with WMD=4.71 (95% CI: 2.76 to 6.67; P<0.001; I 2 =0%); WMD=3.67 (95% CI: 1.08 to 6.26; P=0.006; I 2 =27%) at week 4 and12 after injection, respectively. There was no difference in adverse event between BoNT-A therapy group and control group with OR=1.25 (95% CI: 0.88 to 1.78; P=0.47; I 2 =0%)., Conclusion: As compared with conventional therapy, BoNT-A intra-articular injection have beneficial effects with improved pain score and WOMAC score in adult patients with refractory joint pain.

Two highly symmetrical (3,4)-connected uranyl-organic frameworks (UOFs) were synthesized by a judicious combination of D 3h -symmetrical triangular [UO 2 (COO) 3 ] - and T d symmetrical tetrahedral tetrakis(4-carboxyphenyl)methane (H 4 MTB). These two as-synthesized UOFs possess similar structural units and coordination modes but totally different topological structures, namely ctn net and bor net. Solvent-induced interpenetration and a morphology change are observed. The two compounds exhibit crystal transformation via a dissolution-crystallization process. Adsorption experiments in CH 3 OH solution indicate that both of them can selectively remove positively charged dyes over negatively charged and neutral dyes. Moreover, the electronic structural and bonding properties of the two compounds were systematically explored by density functional theory (DFT) calculations., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aim: To investigate the mechanism by which Qinggan Huoxue Recipe (QGHXR) inhibits epithelial-to-mesenchymal transition (EMT) in rats with alcoholic liver fibrosis (ALF)., Methods: A total of 75 male SD rats were used to induce ALF. Serum biochemical indicators, including alanine aminotransferase, aspartate aminotransferase, laminin and hyaluronidase, were measured. Liver histopathological changes were evaluated using hematoxylin-eosin and Sirius red staining. EMT was examined by analyzing the expression of the epithelial marker E-cadherin and the mesenchymal markers vimentin and fibronectin using RT-PCR and Western blot. The inhibitory effect of QGHXR on EMT markers, as well as its effect on molecules associated with the transforming growth factor (TGF)-β1/Smad signaling pathway, including TGF-β1, Smad3, snail, occludin, ZO-1 and claudin, was also examined., Results: Compared with normal control rats, ALF rats exhibited a decrease in E-cadherin levels (mRNA: ALF 0.16 ± 0.05 vs control 1.00 ± 0.08; protein: ALF 0.09 ± 0.05 vs control 0.70 ± 0.17, P < 0.01) and an increase in vimentin and fibronectin levels (mRNA: 11.43 ± 0.39 vs 1.00 ± 0.19 and 9.91 ± 0.34 vs 1.00 ± 0.44, respectively, P < 0.01; protein: 1.13 ± 0.42 vs 0.09 ± 0.03 and 1.16 ± 0.43 vs 0.09 ± 0.00, respectively, P < 0.01). This indicates that EMT occurred in ALF rats. In addition, the TGF-β1/Smad signaling pathway was activated in ALF rats, as evidenced by the increase in TGF-β1 and snail levels (mRNA: 1.76 ± 0.12 vs 1.00 ± 0.05 and 6.98 ± 0.41 vs 1.00 ± 0.10, respectively, P < 0.01; protein: 1.43 ± 0.05 vs 0.12 ± 0.03 and 1.07 ± 0.29 vs 0.07 ± 0.02, respectively, P < 0.01) and the decrease in Smad3 levels (mRNA: 0.05 ± 0.01 vs 1.00 ± 0.12, P < 0.01; protein: 0.06 ± 0.05 vs 0.89 ± 0.12, P < 0.01). Furthermore, levels of the tight junction markers occludin, ZO-1 and claudin decreased in ALF rats compared with healthy control rats (mRNA: 0.60 ± 0.09 vs 1.00 ± 0.12, 0.11 ± 0.00 vs 1.00 ± 0.12 and 0.60 ± 0.01 vs 1.00 ± 0.08, respectively, P < 0.01; protein: 0.05 ± 0.01 vs 0.87 ± 0.40, 0.09 ± 0.05 vs 0.89 ± 0.18 and 0.04 ± 0.03 vs 0.95 ± 0.21, respectively, P < 0.01). In ALF rats treated with QGHXR, E-cadherin levels increased (mRNA: QGHXR 0.67 ± 0.04 vs ALF model 0.16 ± 0.05, P < 0.01; protein: QGHXR 0.66 ± 0.21 vs ALF model 0.09 ± 0.05, P < 0.01), and vimentin and fibronectin levels decreased (mRNA: 6.57 ± 1.05 vs 11.43 ± 0.39 and 1.45 ± 1.51 vs 9.91 ± 0.34, respectively, P < 0.01; protein: 0.09 ± 0.03 vs 1.13 ± 0.42 and 0.10 ± 0.01 vs 1.16 ± 0.43, respectively, P < 0.01). In addition, QGHXR inhibited the expression of TGF-β1 and increased the expression of Smad3 (mRNA: 1.03 ± 0.11 vs 1.76 ± 0.12, 0.70 ± 0.10 vs 0.05 ± 0.01, respectively, P < 0.05 and P < 0.01; protein: 0.12 ± 0.03 vs 1.43 ± 0.05 and 0.88 ± 0.20 vs 0.06 ± 0.05, respectively, P < 0.01). QGHXR treatment also reduced the levels of the EMT-inducing transcription factor snail (mRNA: 2.28 ± 0.33 vs 6.98 ± 0.41, P < 0.01; protein: 0.08 ± 0.02 vs 1.07 ± 0.29, P < 0.01) and increased the occludin, ZO-1 and claudin levels (mRNA: 0.73 ± 0.05 vs 0.60 ± 0.09, 0.57 ± 0.04 vs 0.11 ± 0.00 and 0.68 ± 0.03 vs 0.60 ± 0.01, respectively, P < 0.01, P < 0.01 and P < 0.05; protein: 0.92 ± 0.50 vs 0.05 ± 0.01, 0.94 ± 0.22 vs 0.09 ± 0.05 and 0.94 ± 0.29 vs 0.04 ± 0.03, respectively, P < 0.01). The effects of QGR and HXR on the TGF-β1/Smad signaling pathway were similar to that of QGHXR; however, the QGR- and HXR-induced changes in vimentin mRNA levels, the QGR-induced changes in fibronectin mRNA levels and the HXR-induced changes in snail and TGF-β1 mRNA levels were not significant., Conclusion: Qinggan Huoxue Recipe inhibits EMT in ALF rats by modulating the TGF-β1/Smad signaling pathway, suggesting that the mechanism underlying the amelioration of ALF induced by QGHXR is associated with this pathway.

Liver transplantation is an effective treatment for patients with end-stage liver disease. Accurate imaging evaluation of the transplanted patient is critical for ensuring that the limited donor liver is functioning appropriately. Ultrasound contrast agents (UCAs), in combination with contrast-specific imaging techniques, are increasingly accepted in clinical use for the assessment of the hepatic vasculature, bile ducts and liver parenchyma in pre-, intra- and post-transplant patients. We describe UCAs, their technical requirements, the recommended clinical indications, image interpretation and the limitations for contrast-enhanced ultrasound applications in liver transplantation.

[Purpose] This review article is designed to expose the application of sonography in shoulder pain after stroke. [Methods] A range of databases was searched to identify articles that address sonography examination, with or without ultrasound guided corticosteroid injection for hemiplegic shoulder pain (HSP). The electronic databases of PubMed, CENTRAL, CINAHL, Cochrane Library, Medline were searched. [Results] According to the articles identified in our databases research, sonographic technique has potential to provide objective measurements in patients with HSP. The main sonography finding of HSP included subacromial subdeltoid (SASD) bursal effusion, tendinosis of the supraspinatus and subscapularis tendon, long head of biceps tendon sheath effusion, and shoulder subluxation. Our analysis also revealed significantly decreased pain score (VAS) and increased passive external rotation degree in the steroid injection group than control group. [Conclusion] The sonography examination is useful for HSP assessment and ultrasound guided technique is recommended for HSP injection treatment.

[Purpose] Lower-limb spasticity after stroke may be associated with worse functional outcome. Our study aim was to establish whether a low-dose botulinum toxin A (BTX-A) injection in subacute stroke patients can improve spasticity, gait, and daily living abilities. [Subjects] Twenty-three subacute stroke patients were randomly allocated to BTX-A treatment group (11 patients) and control group (12 patients). [Methods] In the BTX-A treatment group patients, 200 units BTX-A was injected into the triceps surae (150 iu) and posterior tibial (50 iu) by electrical stimulation-guided. The patients in the control group received the same volume of placebo solution into the same injection locations. Gait analysis (step length, cadence, speed), the 6-min walking test, Fugl-Meyer Assessment (FMA) of the lower limbs, modified Ashworth scale assess (MAS) assessment of the lower limbs, surface electromyography (sEMG), and modified Barthel index (MBI) assessment were performed before and at 4,8 weeks after treatment. [Results] We found that the FMA of the low limbs and MBI were significantly improved in both groups. The gait analysis, FMA, and MBI results in the BTX-A treatment group were better than those in the control group. MAS and surface electromyography (sEMG) showed better improvement of spasticity in the treatment group. [Conclusion] Early low-dose botulinum toxin A (BTX-A) injection in subacute stroke patients into the lower-limb may improve gait, spasticity, and daily living abilities.

Objective: To understand the current status of advanced schistosomiasis patients, so as to provide the reference for improving the medical care of them in Shanggao County., Methods: The data of advanced patients in Shanggao County were collected from the Information Management System for the Advanced Schistosomiasis Chemotherapy and Assistance in Jiangxi Province, and a field survey including the epidemiological investigation, physical examinations, and B ultrasound examinations was performed in 2014. All the data were analyzed statistically and compared with those in 2010., Results: Among the 128 advanced schistosomiasis patients, the male:female ratio was 2.46: 1, the average age was 68.02 ± 6.19 years, and the patients older than 65 years contributed to 64.84% for the all. The proportions of clinically types of ascites, splenomegaly, multiple granuloma in the colon, dwarf, general, and haemorrhage were 57.81%, 12.50%, 2.34%, 0, 26.57%, and 0.78%, respectively. The ultrasound examinations revealed the average diameter of the main trunk of portal vein was 12.70 ± 1.91mm in 2014, which was significantly broader than that of 12.05 ± 0.34mm in 2010 (P < 0.01)., Conclusions: The advanced schistosomiasis patents in Shanggao County decreases with years and shows an aging trend. Some advanced schistosomiasis patients are worse; therefore the chemotherapy and salvation work still should be strengthened.

Background: Finding the optimal approach to repair an inguinal hernia is controversial. Therefore, for the scientific evaluation of the total extraperitoneal (TEP) and Lichtenstein mesh techniques for the repair of inguinal hernia, meta-analyses of randomized controlled trials are necessary., Methods: A complete literature search was conducted in the Cochrane Controlled Trials Register Databases, Pubmed, Embase, International Scientific Institute databases, and Chinese Biomedical Literature Database in various languages., Results: Randomized controlled trials (13), including 3279 patients, were retrieved from the electronic databases. The Lichtenstein group was associated with a shorter operating time; however, results show that TEP repair enabled patients a shorter time to return to work, less chronic pain compared with Lichtenstein operation. There was no significant difference in seromas, wound infections, or neuralgia. There are no statistically significant difference in terms of hernia recurrence when the follow-up time is ≤3 y. When follow-up time is >3 y, TEP repair shows a higher recurrence rate compared with Lichtenstein repairs., Conclusions: There was insufficient evidence to determine the greater effectiveness between TEP and Lichtenstein mesh techniques. In future research, it is necessary for subgroup analyses of unilateral primary hernias, recurrent hernias, and simultaneous bilateral repair to be conducted to define the indications for the TEP approach., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Recently, acetylcholinesterase (AChE, EC 3.1.1.7) has received increased attention in the field of environmental sciences. Evaluation of the effects of environmental contaminants on AChE enzymatic activity not only can reflect, to some extent, the interference with the nervous system, but also can be used for monitoring pollution. Our previous study showed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) suppressed neuronal AChE enzymatic activity via transcriptional downregulations mediated by aryl hydrocarbon receptor. In the present study, the effects of several other dioxin-like compounds (DLCs) on neuronal AChE activity were determined, including 1,2,3,7,8-pentachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, 2,3,4,7,8-pentachlorodibenzofuran, and 2,3,7,8-tetrabromodibenzo-p-dioxin. The results showed that the enzymatic activity of AChE was significantly decreased by approximately 15-30 % after exposure to a certain concentrations of the DLCs, whereas incubating neuronal cell lysates directly with these DLCs did not inhibit AChE enzyme. Subsequent molecular mechanism study showed that these chemicals could decrease ACHE promoter activity, as well as AChE T mRNA expression, thereby suggesting the involvements of transcriptional regulation in these effects. These findings on DLCs are similar with those on 2,3,7,8-TCDD, pointing to the possibility that exposure to dioxin and DLCs, which frequently coexist in the contaminated environments, may concurrently interfere with the cholinergic functions via AChE.

Aim: To characterize the clinical, radiological, endoscopic and pathological features of intestinal tuberculosis (ITB) and primary small intestinal lymphoma (PSIL)., Methods: This was a retrospective study from February 2005 to October 2012 of patients with a diagnosis of ITB (n = 41) or PSIL (n = 37). All patients with ITB or PSIL underwent computed tomography (CT) and pathological examination. Thirty-five patients with ITB and 32 patients with PSIL underwent endoscopy. These patients were followed for a further 18 mo to ascertain that the diagnosis had not changed. Clinical, endoscopic, CT and pathological features were compared between ITB and PSIL patients., Results: Night sweating, fever, pulmonary TB and ascites were discovered significantly more often in ITB than in PSIL patients (P < 0.05), however, abdominal mass, hematochezia and intestinal perforation were found significantly more frequently in PSIL than in ITB patients (P < 0.05). Ring-like and rodent-like ulcers occurred significantly more often in ITB than in PSIL patients (P < 0.05), however, enterorrhagia and raised lesions were significantly more frequent in PSIL than in ITB patients (P < 0.05). The rate of granuloma was significantly higher in ITB than in PSIL patients (87.8% vs 13.5%, χ(2) = 43.050, P < 0.05), and the incidence of confluent granulomas with caseous necrosis was significantly higher in ITB than in PSIL patients (47.2% vs 0.0%, χ(2) = 4.034, P < 0.05). Multi-segmental lesions, mural stratification, mural gas sign, and intestinal stricture were more frequent in ITB than in PSIL patients (P < 0.05), however, a single-layer thickening of bowel wall, single segmental lesions, and intussusception were more common in PSIL than in ITB patients (P < 0.05). Necrotic lymph nodes, comb sign and inflammatory mass were more frequent in ITB than in PSIL patients (P < 0.05). The bowel wall enhancement in ITB patients was greater than that in PSIL patients (P < 0.05), while the thickening and lymph node enlargement in PSIL patients were higher than those in ITB patients (P < 0.05)., Conclusion: Combined evaluation of clinical, radiological, endoscopic and pathological features is the key to differentiation between ITB and PSIL.

In this article, we have examined the motility-related effects of weak power frequency magnetic fields (MFs) on the epidermal growth factor receptor (EGFR)-sensitive motility mechanism, including the F-actin cytoskeleton, growth of invasive protrusions and the levels of signal molecules in human amniotic epithelial (FL) cells. Without extracellular EGF stimulation, the field stimulated a large growth of new protrusions, especially filopodia and lamellipodia, an increased population of vinculin-associated focal adhesions. And, an obvious reduction of stress fiber content in cell centers was found, corresponding to larger cell surface areas and decreased efficiency of actin assembly of FL cells in vitro, which was associated with a decrease in overall F-actin content and special distributions. These effects were also associated with changes in protein content or distribution patterns of the EGFR downstream motility-related signaling molecules. All of these effects are similar to those following epidermal growth factor (EGF) stimulation of the cells and are time dependent. These results suggest that power frequency MF exposure acutely affects the migration/motility-related actin cytoskeleton reorganization that is regulated by the EGFR-cytoskeleton signaling pathway. Therefore, upon the MF exposure, cells are likely altered to be ready to transfer into a state of migration in response to the stimuli.

Backgrounds: Autophagy is an important process in the pathogenesis of diabetes and plays a critical role in maintaining cellular homeostasis. However, the autophagic response and its mechanism in diabetic vascular endothelium remain unclear., Methods and Results: We studied high-glucose-induced renin-angiotensin system (RAS)-mitochondrial damage and its effect on endothelial cells. With regard to therapeutics, we investigated the beneficial effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) against high-glucose-induced endothelial responses. High glucose activated RAS, enhanced mitochondrial damage and increased senescence, apoptosis and autophagic-responses in endothelial cells, and these effects were mimicked by using angiotensin II (Ang). The use of an ACEI or ARB, however, inhibited the negative effects of high glucose. Direct mitochondrial injury caused by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) resulted in similar negative effects of high glucose or Ang and abrogated the protective effects of an ACEI or ARB. Additionally, by impairing autophagy, high-glucose-induced senescence and apoptosis were accelerated and the ACEI- or ARB-mediated beneficial effects were abolished. Furthermore, increases in FragEL™ DNA Fragmentation (TUNEL)-positive cells, β-galactosidase activation and the expression of autophagic biomarkers were revealed in diabetic patients and rats, and the treatment with an ACEI or ARB decreased these responses., Conclusions: These data suggest that autophagy protects against senescence and apoptosis via RAS-mitochondria in high-glucose-induced endothelial cells., (© 2014 S. Karger AG, Basel.)

Objective: To analyze the present epidemic status of drug-resistant Mycobacterium tuberculosis (MTB) in Shandong Province of China, as compared with findings of survey for drug-resistant MTB in 1997, and therefore to provide valuable data for making the current control policy of drug-resistant MTB., Methods: From October 2004 to December 2011, the culture positive sputum samples of all 5916 new registered sputum smear-positive TB patients at the county-level TB dispensaries were tested for drug susceptibility. Finally 5542 cases with test results were included in the analysis. Of the total cases, 4198 were male and 1344 were female. The age range of the patients were 15 to 92 years old and the average age was (51 ± 20) years old, among whom, 1304 were ≤ 29 years old, 2106 were from 30 to 59 years old and 2132 were ≥ 60 years old. Of all the cases, 4332 (78.2%) only received initial treatment and 1210 (21.8%) received retreatment. The SPSS 13.0 was used for statistical analysis and χ(2) test was used to compare category, gender, and age groups of patients., Results: The total drug resistance (TDR) rate was 19.4% (1075/5542), which was lower than 23.4% (288/1229) in 1997 in Shandong Province (χ(2) = 10.193, P < 0.01). The rates of single drug resistance (SDR), multidrug resistance (MDR) and poly-drug resistance (PDR) were 11.3% (629/5542), 3.7% (203/5542) and 4.4% (243/5542), respectively. The TDR rate in patients with initial treatment was 19.0% (822/4332), and 62.7% (515/822) of which was SDR. The TDR rate of patients with retreatment was 20.9% (253/1210), and 54.9% (139/253) of which tended to be MDR or PDR. Among TDR patients, those with initial treatment accounted for 76.5% (822/1075) and SDR patients accounted for 58.5% (629/1075). The MDR rate of patients with initial treatment was 2.9% (124/4332) and the rate of patients with retreatment was 6.5% (79/1210), the differences being significant (χ(2) = 36.032, P < 0.01). The TDR rate, initial TDR rate, and retreatment TDR rate in males were 19.9% (834/4198), 19.5% (641/3287), and 21.2% (193/911), respectively, as compared to 17.9% (241/1344), 17.3% (181/1045), and 20.1% (60/299) in females, the differences being not significant (χ(2) = 0.170-2.452, P > 0.05)., Conclusions: The drug-resistant TB control work in Shandong Province has made great achievements in recent years. However, patients with initial treatment were more likely to have drug-resistant MTB. Therefore the future control work should focus on early detection, effective treatment and management to control the spread of drug-resistant MTB.

Human carboxylesterase (CES) 1A and CES2, two major forms of human CES, dominate the pharmacokinetics of most prodrugs such as imidapril and irinotecan (CPT-11). Antihypertensive drugs are often prescribed for clinical therapy concurrently with others. Moreover, two or more antihypertensive drugs are ubiquitously combined. The influences of antihypertensive drugs on the activity of CES remain undefined. In the present study, the inhibitory effects of 17 antihypertensive drugs on the CES1A1 and CES2 activities were evaluated. Imidapril and CPT-11 were used as substrates and cultured with liver microsomes in vitro. The imidapril hydrolase activities by recombinant CES1A1 and human liver microsomes (HLM) were intensely inhibited by telmisartan and nitrendipine (K(i) = 0.49 ± 0.09 and 1.12 ± 0.39 µM for CES1A1, 1.69 ± 0.17 µM and 1.24 ± 0.27 µM for HLM, respectively). However, other drugs did not exert strong inhibition. The enzyme hydrolase activity of recombinant CES2 was substantially inhibited by diltiazem and verapamil (K(i) = 0.25 ± 0.02 and 3.84 ± 0.99 µM, respectively). Hence, diltiazem, verapamil, nitrendipine and telmisartan may attenuate the drug efficacy of catalyzed prodrugs by changing the activities of CES1A1 and CES2.

Study Design: A retrospective radiographical study investigated the sagittal alignment in healthy Chinese girls and Chinese girls with idiopathic thoracic scoliosis (T-AIS)., Objective: To evaluate the sagittal alignment of the pelvis and spine in Chinese girls with idiopathic scoliosis and healthy girls and to assess whether the pelvic morphology differed between white and Chinese girls with AIS., Summary of Background Data: It has been shown that patients with AIS have an abnormal spinopelvic balance and pelvic morphology. Race is a determinant factor of sagittal spinal alignment and serves as a reminder when planning surgical reconstruction for spinal deformity. Until now, there have been no studies documenting the sagittal lumbosacral spine morphology in Chinese girls with T-AIS., Methods: In this study, 95 patients with T-AIS and 33 healthy age-matched adolescents were recruited consecutively. Sagittal spinal and pelvic parameters were measured from the standing lateral radiograph, including thoracic kyphosis (TK), lumbar lordosis (LL), upper arc of LL, lower arc of LL, pelvic incidence (PI), sacrum slope (SS), and pelvic tilt (PT). Analysis of variance was used in the comparison of each dependent variable between patients with AIS and healthy adolescents. The relations between all parameters were determined via Pearson correlation coefficient (r)., Results: For all the sagittal parameters, only the TK and the upper arc of the LL showed significant differences between girls with AIS and healthy girls. The LL, lower arc of the LL, and 3 pelvic parameters were similar for both groups. The TK was found to be strongly correlated with LL and the upper arc of the LL in both groups. However, the TK was not related to the lower arc of the LL, nor were the 3 pelvic parameters in either group. In addition, LL was found to be associated with PI and SS in both groups. The lower arc of the LL was also correlated with PI for both groups. The PI was related to PT and SS in both groups; however, no correlation was found between PT and SS. In this study, the TK (15.7°), SS (35.1°), and PI (44.2°) were found to be significantly lower in Chinese patients with T-AIS than the values reported in the AIS cohort., Conclusion: In our study, the Chinese girls with T-AIS had similar PI, PT, and SS values when compared with the age-matched healthy girls. There were significant differences in pelvic morphology between Chinese and white girls with AIS. These results suggest that race may influence an individual's spinopelvic morphology. Although we have shown that the TK could affect LL through the upper arc of the LL directly, the evaluation of the thoracolumbar morphology of T-AIS before surgery is important for surgical planning.

Thirty-five 3-aryl-4-arylaminofuran-2(5H)-one derivatives were designed, prepared and tested for their inhibitory activity against tyrosyl-tRNA synthetase. Out of these compounds, 3-(3-bromophenyl)-4-(3,5-dichlorophenylamino)furan-2(5H)-one (35) was the most active with IC(50) of 0.09 ± 0.02 μM. The structure-activity relationship revealed that introduction of chlorine atoms at both meta positions of aniline moiety significantly increased the enzyme inhibitory activity. The results of antibacterial assay revealed that the tested compounds showed good activity against Gram-positive bacteria, with 35 being the most potent with MIC(50) of 0.06 μg/mL against Staphylococcus aureus ATCC 25923. Molecular docking of 35 into S. aureus tyrosyl-tRNA synthetase active site was also performed. The inhibitor snugly fitting the active site may well explain its excellent inhibitory activity., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Ambient particulate matter (PM) has been reported to be associated with increased respiratory, cardiovascular, and malignant lung diseases. The aim of the present study was to investigate the variability of the DNA-damage induced by thoracic particles (PM( 10)) sampled in different locations and seasons (2006) in Dalian, China, in human hepatoma G2 (HepG2) cells. Significant differences in percentage of tail DNA induced by the extractable organic matter of PM(10) were revealed between summer and winter seasons and among monitoring sites in single cell gel electrophoresis (SCGE) assay. The percentage of tail DNA in HepG2 cells significantly increased in a dose-dependent manner after exposure to 7.5 and 30 μg/mL extractable organic matter of PM(10) for 1 hour. In order to clarify the underlying mechanisms, we evaluated the level of reactive oxygen species (ROS) production with the 2, 7-dichloro-fluorescein diacetate (DCFH-DA) assay. Significantly increased level of ROS was observed in HepG2 cells at higher concentrations (15 and 30 μg/mL). Significantly increased levels of 8-hydroxydeoxyguanosine (8-OHdG) were also shown in HepG2 cells. In this study, the accumulation of nuclear factor kappa B (NF-κB) p65 protein induced by the extractable organic matter of PM(10) was detected by western blotting in HepG2 cells, and the protein expression of NF-κB p65 significantly increased after the treatment with 30 μg/mL extractable organic matter of PM(10) for 24 hours. These results indicate that the extractable organic matter of PM(10) causes DNA strand breaks in HepG2 cells, and significant differences in percentage of tail DNA in dependence on locality and season are revealed. The extractable organic matter of PM(10) exerts DNA damage effects in HepG2 cells, probably through oxidative DNA damage induced by intracellular ROS, increase of 8-OHdG formation, and protein expression of NF-κB p65.