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Intestinal submucosal fibrovascular hamartoma is considered as a rare intestinal lesion. We present the case of a 63-year-old female with abdominal symptoms, bleeding, and increased serum tumor markers. The abdominal ultrasound revealed that the left abdominal intestinal wall and mesentery were thickened with enlarged multiple lymph nodes, suggesting intestinal obstruction. Other imaging findings confirmed the ultrasound findings. Histopathology of the removed lesion provided the diagnosis of intestinal submucosal fibrovascular hamartoma with hemorrhage, inflammation, and amyloidosis. Intestinal submucosal fibrovascular hamartoma is a hemorrhagic lesion with macroscopic tumor due to the abnormal mixing of the organ's normal components, which still remains a challenge for clinicians and pathologists. We consider routine abdominal ultrasonography and contrast-enhanced ultrasonography (SICUS) to be safe and effective in the diagnosis of intestinal neoplastic lesions.

Abstract. The study was to investigate the clinical characteristics and significance of antinuclear antibody (ANA) cytoplasmic patterns in ANCA-associated vasculitis (AAV) from Southwest China. A retrospective study including 232 AAV patients from Peoples Hospital of Deyang City was performed. These included 115 patients with ANA cytoplasmic pattern as observation group and 117 patients without ANA cytoplasmic pattern as control group. Chest involvement (60.00 vs 46.15, P = .035), cardiovascular involvement (5.21 vs 29.91, P

Human epidermal growth factor 2 (HER2)+ breast cancer is considered the most dangerous type of breast cancers. Herein, we used bioinformatics methods to identify potential key genes in HER2+ breast cancer to enable its diagnosis, treatment, and prognosis prediction. Datasets of HER2+ breast cancer and normal tissue samples retrieved from Gene Expression Omnibus and The Cancer Genome Atlas databases were subjected to analysis for differentially expressed genes using R software. The identified differentially expressed genes were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses followed by construction of protein-protein interaction networks using the STRING database to identify key genes. The genes were further validated via survival and differential gene expression analyses. We identified 97 upregulated and 106 downregulated genes that were primarily associated with processes such as mitosis, protein kinase activity, cell cycle, and the p53 signaling pathway. Visualization of the protein-protein interaction network identified 10 key genes ( CCNA2 , CDK1 , CDC20 , CCNB1 , DLGAP5 , AURKA , BUB1B , RRM2 , TPX2 , and MAD2L1 ), all of which were upregulated. Survival analysis using PROGgeneV2 showed that CDC20 , CCNA2 , DLGAP5 , RRM2 , and TPX2 are prognosis-related key genes in HER2+ breast cancer. A nomogram showed that high expression of RRM2 , DLGAP5 , and TPX2 was positively associated with the risk of death. TPX2 , which has not previously been reported in HER2+ breast cancer, was associated with breast cancer development, progression, and prognosis and is therefore a potential key gene. It is hoped that this study can provide a new method for the diagnosis and treatment of HER2 + breast cancer.

Medicinal insects play an important role in the treatment of refractory diseases due to their unique and rich pharmacological activities. However, compared to plants, microorganisms, and marine organisms, medicinal insects have been largely ignored. Some small molecules isolated from insects are known to have defensive effects, but their majority roles remain unknown. In-depth research on the small molecules of medicinal insects has been conducted in recent years. Then alkaloids, dopamine derivatives, nucleoside derivatives, and other components are obtained. Among them, dopamine derivatives are a unique class of components from medicinal insects. Thus, we present a comprehensive overview of chemical structures and biological activities of dopamine derivatives from some medicinal insects, which will bring more attention to other researchers for further chemical and biological investigations on the unique dopamine derivatives as well as medicinal insects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Few nursing informatics studies focus on selecting nursing diagnoses for critical patients. The absence of data about nursing clinical judgment in the care of patients with cerebral hemorrhage greatly hinders research progress in evidence-based care. A stratified, retrospective study analyzed 115 electronic "intelligent" nursing information system nurse assessments and nursing diagnoses. Data were documented from April 2019 to November 2020 for critically ill patients admitted with cerebral hemorrhage in a 10-bed medical ICU at a 1500-bed tertiary facility, Henan Honliv Hospital, in Henan Province, China. In the selection of nursing diagnoses among nurses of stratified competencies (novice to expert), novice and experienced nurses were found to have significant variances in selecting nursing diagnoses for critically ill patients with cerebral hemorrhage. Novice nurses more frequently selected the Activity Intolerance Risk diagnosis as an initial diagnosis ( P = .025). Experienced nurses selected the Fluid Volume Excess Risk diagnosis more frequently ( P = .003). Consequently, nursing information systems are important in evaluating professional practice. The access to structured, standardized nursing data for the complete nursing process enables nurse managers to comprehensively analyze the nursing care given to patients, the distribution of patient nursing diagnoses, and the status of patient care risks., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Engineering excitation wavelength of photosensitizers (PSs) for enhanced reactive oxygen species (ROS) generation has inspired new windows for opportunities, enabling investigation of previously impracticable biomedical and photocatalytic applications. However, controlling the wavelength corresponding to operating conditions remains challenging while maintaining high ROS generation. To address this challenge, we implement a wavelength-engineerable imidazolium-based porous organic photocatalytic ROS generation system (KUP system) via a cost-effective one-pot reaction. Remarkably, the optimal wavelength for maximum performance can be tuned by modifying the linker, generating ROS despite the absence of metal ions and covalently attached heavy atoms. We demonstrate that protonated polymerization exclusively enables photosensitization and closely interacts with oxygen related to the efficiency of photosensitizing. Furthermore, superior tumor eradication and biocompatibility of the KUP system were confirmed through bioassays. Overall, the results document an unprecedented polymerization method capable of engineering wavelength, providing a potential basis for designing nanoscale photosensitizers in various ROS-utilizing applications., (© 2023. The Author(s).)

Immune checkpoint inhibitors (ICIs) change the prognosis of many cancer patients. With the increasing use of ICIs, immune-related adverse events are occurring, including acute kidney injury (AKI). This study aimed to assess the incidence of AKI during ICI treatment and its risk factors and impact on mortality. Patients treated with ICIs at the First Medical Center of the Chinese PLA General Hospital from January 1, 2014, to December 30, 2019, were consecutively enrolled, and risk factors affecting AKI development in patients treated with ICIs were analyzed using univariate and multivariate logistic regression. Medical record surveys and telephone inquiry were used for follow-up, and Kaplan-Meier survival analysis and Cox regression were used to analyze independent risk factors for death. Among 1615 patients, 114 (7.1%) had AKI. Multivariate logistic regression analysis showed that anemia, Alb < 30 g/L, antibiotic use, diuretic use, NSAID use and proton pump inhibitor use were independent risk factors for AKI development in patients treated with ICIs. Stage 2 or 3 AKI was an independent risk factor for nonrecovery of renal function after AKI onset. Multivariate Cox regression analysis showed that anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs, while high baseline BMI, other tumor types, ACEI/ARB use, and chemotherapy use were protective factors for patient death. AKI occurs in 7.1% of patients treated with ICIs. Anemia, Alb < 30 g/L, and combined medication use are independent risk factors for AKI in patients treated with ICIs. Anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs., (© 2022. The Author(s).)

Photodynamic therapy combined with immunogenic cell death has been proposed to overcome the unsolvable problems of single therapy, such as high levels of tumor recurrence and treatment resistance of tumors. Previous works on this theme have mostly concentrated on endoplasmic reticulum (ER)-stressed damage-associated molecular patterns (DAMPs), ignoring the secretion and function of mitochondria-related DAMPs. Herein, our work reports two intersystem crossing photosensitizers based on well-designed multiarylpyrrole structures and draws valuable attention to mitochondria-related DAMP-TFAM (mitochondrial transcription factor) when cancer cells are under forceful oxidative stress. The tumors vanished, and immunogenic experiments were applied to illuminate the advantages of double treatment. Our discovery of new mitochondria-related DAMPs compensates for the lack of ER-stressed DAMPs and offers an innovative target for immunity therapy., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To explore the internal mechanism of hepatocellular carcinoma (HCC) induced by chronic hepatitis B virus (HBV) infection., Methods: L02, HepG2 and Huh7 cells stably overexpressing HBV preS1 antigen were analyzed by flow cytometry, qRT-PCR and tumorigenesis in nude mice to evaluate the effect of preS1 antigen in HBV-related hepatocarcinogenesis., Results: Our results showed that the expression of cancer stem cell (CSCs) related factors and cell surface markers in preS1 overexpressing cells were up-regulated, and the tumorigenicity of these cells was enhanced in nude mice. In addition, preS1 overexpression could down-regulate the expression of major histocompatibility complex Ⅰ (MHC-Ⅰ). The expression of MHC-Ⅰ on the cell surface could be restored by adding interferon gamma (IFN-γ) in the process of cell culturing and the tumorigenicity of cells in nude mice could thus be reduced., Conclusion: Based on the above results, we believe that preS1 is a carcinogen of HBV and that it promotes the formation of liver cancer through down regulating MHC-Ⅰ on the surface of hepatocytes., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

The study examined the skin histomorphology and biochemistry in mature ovariectomized rats treated and not treated with estrogen. Biochemical parameters (superoxide dismutase, malondialdehyde, and hydroxyproline content) were measured in dorsal skin samples collected in 50 days after surgery. The morphology of dorsal skin was analyzed under a microscope. In ovariectomized rats, the skin levels of superoxide dismutase and hydroxyproline were significantly lower, while the superoxide dismutase content was significantly higher than in shamoperated animals (p<0.05). Estrogen therapy significantly increased the levels of superoxide dismutase and hydroxyproline and reduced superoxide dismutase level in ovariectomized rats in comparison with the corresponding parameters in untreated ovariectomized animals (p<0.05). Histomorphological analysis of the skin from non-treated ovariectomized rats revealed reduced vascularization and lower density of papillary capillaries in comparison with these parameters in sham-operated controls; estrogen treatment prevented these changes. We concluded that ovariectomized rats can be employed as a model of aging skin in menopause., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Aldehyde dehydrogenase (ALDH), a cancer stem cell biomarker, is related to drug resistance. Co-treatment of anti-cancer drug (CPT) and ALDH inhibitor (DEAB) can overcome the drug resistance of cancer stem cells (CSCs) and finally cure cancers without relapse. We herein introduce a prodrug (DE-CPT) - consisting of 1,3-oxathiolane as an ROS responsive scaffold, and an aldehyde protecting group of DEAB - to deliver the CPT and DEAB upon reaction with ROS. From tests of the sphere-forming ability and CSC marker subpopulation, we found that DE-CPT efficiently decreases the CSCs population and kills the cancer cells.

The parasternal intercostal is an obligatory inspiratory muscle working in coordination with the diaphragm, apparently sharing a common pathway of neural response. This similarity has attracted clinical interest, promoting the parasternal as a noninvasive alternative to the diaphragm, to monitor central neural respiratory output. However, this role may be confounded by the distinct and different functions of the costal and crural diaphragm. Given the anatomic location, parasternal activation may significantly impact the chest wall via both mechanical shortening or as a "fixator" for the chest wall. Either mechanical function of the parasternal may also impact differential function of the costal and crural. The objectives of the present study were, during eupnea and hypercapnia, 1 ) to compare the intensity of neural activation of the parasternal with the costal and crural diaphragm and 2 ) to examine parasternal recruitment and changes in mechanical action during progressive hypercapnia, including muscle baseline length and shortening. In 30 spontaneously breathing canines, awake without confounding anesthetic, we directly measured the electrical activity of the parasternal, costal, and crural diaphragm, and the corresponding mechanical shortening of the parasternal, during eupnea and hypercapnia. During eupnea and hypercapnia, the parasternal and costal diaphragm share a similar intensity of neural activation, whereas both differ significantly from crural diaphragm activity. The shortening of the parasternal increases significantly with hypercapnia, without a change in baseline end-expiratory length. In conclusion, the parasternal shares an equivalent intensity of neural activation with the costal, but not crural, diaphragm. The parasternal maintains and increases its active inspiratory shortening during augmented ventilation, despite high levels of diaphragm recruitment. Throughout hypercapnic ventilation, the parasternal contributes mechanically; it is not relegated to chest wall fixation. NEW & NOTEWORTHY This investigation directly compares neural activation of the parasternal intercostal muscle with the two distinct segments of the diaphragm, costal and crural, during room air and hypercapnic ventilation. During eupnea and hypercapnia, the parasternal intercostal muscle and costal diaphragm share a similar neural activation, whereas they both differ significantly from the crural diaphragm. The parasternal intercostal muscle maintains and increases active inspiratory mechanical action with shortening during ventilation, even with high levels of diaphragm recruitment.

Achieving self-assembled nanostructures with ultra-small feature sizes (e. g., below 5 nm) is an important prerequisite for the development of block copolymer lithography. In this work, the preparation and self-assembly of a series of giant molecules composed of vinyl polyhedral oligomeric silsesquioxane (VPOSS) tethered with monodispersed oligo(L-lactide) chains are presented. Small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) results demonstrate that ultra-small domain sizes (down to 3 nm) of phase separated lamellar morphology are achieved in bulk, driven by the strong tendency and fast kinetics for crystallization of VPOSS moieties. Moreover, upon gamma ray radiation, VPOSS cages in the lamellar structure can be crosslinked via polymerization of the vinyl groups. After pyrolysis at high temperature, ultra-thin two-dimensional nano-silica sheets can be obtained., (© 2021 Wiley-VCH GmbH.)

The inevitable challenge in conventional chemotherapy is to deliver the anticancer drugs to the dense population of tumors cells while minimizing the drug-associated side effects on the normal cells. Cancer cells' preference for glycolysis for energy production is well recognized. Intuitively, taking advantage of such cancer-associated metabolism would be a promising strategy for anticancer drug delivery with minimal side effects. In this investigation, we have designed a binary prodrug PDOX as a sequential drug delivery regimens to realize the combination therapy for cancer. As cancer cells exhibit abrupt metabolism with elevated pyruvate dehydrogenase kinase (PDK) activity, dichloroacetic acid (DCA, a well-known PDK inhibitor) was used in combination with anticancer drug doxorubicin (DOX). The designed molecular prodrug was activated selectively by cancer-associated esterase to deliver DCA and DOX, respectively, and induced synergetic effects. Hence, sequential targeted delivery of molecular prodrug PDOX offers a promising approach to overcome the offside drug toxicity, pharmacokinetics, and biodistribution of individuals and provide an alternative option for cancer treatment.

Melanoma is the most threatening form of metastatic skin cancer that develops from melanocytes and causes a large majority of deaths due to poor therapeutic prognosis. It has significant limitations in treatment because it shows great resistance to chemotherapy, radiotherapy, and other therapeutic methods. A noninvasive and clinically accepted therapeutic modality, photodynamic therapy (PDT), is a promising treatment option, but it is limitedly applied for melanoma skin cancer treatment. This is because most of the photosensitizers are unlikely to be expected to have a remarkable effect on melanoma due to drug efflux by melanin pigmentation and intrinsic antioxidant defense mechanisms. Moreover, melanin is a dominant absorber in the spectral region of 500-600 nm that can cause the decreased photoreaction efficiency of photosensitizers. Herein, to overcome these drawbacks, we have developed a phenylthiourea-conjugated BODIPY photosensitizer ( PTUBDP ) for tyrosinase-positive melanoma-targeted PDT. In light of our results, it exhibited an enhanced cytotoxic efficacy compared to BDP, a parallel PDT agent that absence of phenylthiourea unit. PTUBDP shows outstanding effects of increased oxidative stress by an enhanced cellular uptake of the tyrosinase positive melanoma cell line (B16F10). This work presents increased therapeutic efficacy through the combined therapeutic approach, enabling enhanced reactive oxygen species (ROS) generation as well as overcoming the critical limitations of melanoma.

Background: In recent years, the number of invasive aspergillus infection cases caused by Aspergillus lentulus ( A. lentulus ) has gradually increased and this fungus is usually difficult to distinguish from Aspergillus fumigatus in morphology. All of these presents a great challenge to the treatment of invasive fungal infections caused by A. lentulus . The present study aims to discuss the antifungal resistance, virulence and inflammatory factors' changes after the infection of larvae of A. lentulus separated from patients with chronic obstructive pulmonary disease (COPD) to reflect the host immune response., Methods: A. lentulus isolated from COPD patients was identified by morphology and molecular biology, and its drug sensitivity was determined in vitro . Then the virulence factors and inflammatory response related factors of A. lentulus were determined by the model of A. lentulus infecting larvae. These were divided into three groups: A. lentulus standard strain, A. lentulus strain isolated from patients; PBS control. The infection model was formed by injecting the suspension of A. lentulus at a concentration of 1×10 6 CFU into larvae, in order to determine the (1,3)-β-D-glucan and galactomannan levels, and determine the caspase-1 and TNF-α concentration in Galleria mellonella larvae by RT-PCR., Results: The results revealed that A. lentulus had good sensitivity to itraconazole, voriconazole and micafungin, while (1,3)-β-D-glucan was negative in the two groups. The level of galactomannan in the two groups was higher than that in the control group, and the difference was statistically significant (P<0.05). However, there was no statistical difference between the standard strain group and patient strain group (P>0.05). After the infection of larvae, caspase-1 and TNF-α in the Galleria mellonella larvae increased in the two groups, and these elevated levels were statistically significant in both groups (P<0.05). However, there was no significant difference between the two groups (P>0.05)., Conclusions: There is no significant difference in virulence factor and host inflammatory response between A. lentulus isolated from COPD patients and standard strains. Galactomannan has more advantages in the early detection of A. lentulus invasive infection. Furthermore, the caspase-1-mediated inflammasome pathway may be involved in the host immune response to A. lentulus ., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-961). All authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Neurodegenerative diseases are debilitating disorders that feature progressive and selective loss of function or structure of anatomically or physiologically associated neuronal systems. Both chronic and acute neurodegenerative diseases are associated with high morbidity and mortality along with the death of neurons in different areas of the brain; moreover, there are few or no effective curative therapy options for treating these disorders. There is an urgent need to diagnose neurodegenerative disease as early as possible, and to distinguish between different disorders with overlapping symptoms that will help to decide the best clinical treatment. Recently, in neurodegenerative disease research, fluorescent-probe-mediated biomarker visualization techniques have been gaining increasing attention for the early diagnosis of neurodegenerative diseases. A survey of fluorescent probes for sensing and imaging biomarkers of neurodegenerative diseases is provided. These imaging probes are categorized based on the different potential biomarkers of various neurodegenerative diseases, and their advantages and disadvantages are discussed. Guides to develop new sensing strategies, recognition mechanisms, as well as the ideal features to further improve neurodegenerative disease fluorescence imaging are also explored., (© 2020 Wiley-VCH GmbH.)

Background: Diffusion magnetic resonance (MR) characteristics are a predictive imaging biomarker for survival benefit in recurrent glioblastoma treated with anti-vascular endothelial growth factor (VEGF) therapy; however, its use in large volume recurrence has not been evaluated., Objective: To determine if diffusion MR characteristics can predict survival outcomes in patients with large volume recurrent glioblastoma treated with bevacizumab or repeat resection., Methods: A total of 32 patients with large volume (>20 cc or > 3.4 cm diameter) recurrent glioblastoma treated with bevacizumab and 35 patients treated with repeat surgery were included. Pretreatment tumor volume and apparent diffusion coefficient (ADC) histogram analysis were used to phenotype patients as having high (>1.24 μm2/ms) or low (<1.24 μm2/ms) ADCL, the mean value of the lower peak in a double Gaussian model of the ADC histogram within the contrast enhancing tumor., Results: In bevacizumab and surgical cohorts, volume was correlated with overall survival (Bevacizumab: P = .009, HR = 1.02; Surgical: P = .006, HR = 0.96). ADCL was an independent predictor of survival in the bevacizumab cohort (P = .049, HR = 0.44), but not the surgical cohort (P = .273, HR = 0.67). There was a survival advantage of surgery over bevacizumab in patients with low ADCL (P = .036, HR = 0.43) but not in patients with high ADCL (P = .284, HR = 0.69)., Conclusion: Pretreatment diffusion MR imaging is an independent predictive biomarker for overall survival in recurrent glioblastoma with a large tumor burden. Large tumors with low ADCL have a survival benefit when treated with surgical resection, whereas large tumors with high ADCL may be best managed with bevacizumab., (Copyright © 2020 by the Congress of Neurological Surgeons.)

The abnormality of the plasma membrane (PM) is an important biomarker for cell status and many diseases. Hence, visualizing the PM, especially in complex systems, is an emerging field in the life sciences, especially in low-resource settings. Herein, we developed a water-soluble PM-specific probe utilizing electrostatic and hydrophobic interaction strategies with aggregation-induced emission as the signal output. The probe could image the PM with many advanced features (wash-free, ultrafast staining process, excellent PM specificity, and good biocompatibility), which were demonstrated by the PM imaging of neurons. The probe allowed for the first time the imaging of erythrocytes in the complex brain environment through a fluorescence-based method. Moreover, the PM of the epidermal and partial view of the eyeball structure of live zebrafish are also revealed., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Targeted next-generation sequencing (NGS) is frequently obtained at the University of California, Los Angeles (UCLA) for clinical characterization of CNS tumors. In this study, we describe the diagnostic reliability of the Foundation Medicine (FM) targeted NGS platform and its ability to explore and identify tumor characteristics of prognostic significance in gliomas., Methods: Neuro-oncology patients seen at UCLA who have received FM testing between August 2012 and March 2019 were included in this study, and all mutations from FM test reports were recorded. Initial tumor diagnoses and diagnostic markers found via standard clinical methods were obtained from pathology reports. With overall and progression-free survival data, elastic net regularized Cox regression and Cox proportional hazards models were used to determine whether any mutations of unknown significance detected by FM could predict patient outcome in glioblastoma (GBM)., Results: Six hundred and three samples tested by FM from 565 distinct patients were identified. Concordance of diagnostic markers was high between standard clinical testing methods and FM. Oligodendroglial markers detected via FM were highly correlated with 1p19q codeletion in IDH mutated gliomas. FM testing of multiple tumor samples from the same patient demonstrated temporal and spatial mutational heterogeneity. Mutations in BCORL1 , ERBB4 , and PALB2 , which are mutations of unknown significance in GBM, were shown to be statistically significant in predicting patient outcome., Conclusions: In our large cohort, we found that targeted NGS can both reliably and efficiently detect important diagnostic markers in CNS tumors., (© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Delirium is very common among patients with polytrauma, although no suitable means exist to feasibly reduce the incidence and duration of delirium in these patients. Recent reports have suggested that continuous intravenous (IV) infusions of dexmedetomidine, rather than benzodiazepine, be administered for sedation to reduce the duration of delirium in this population. However, serum neuron-specific enolase (NSE), S100 calcium binding protein B (S100B), and brain-derived neurotrophic factor (BDNF) levels have not yet been investigated in polytrauma patients who received sedation with dexmedetomidine rather than other conventional sedatives. The aim of this study was to assess the association of blood BDNF, NSE, and S100B with the occurrence of delirium among polytrauma patients who had been sedated with dexmedetomidine., Materials and Methods: Consecutive patients were randomly assigned to 1 of 2 treatment study groups, namely the "dexmedetomidine group" or the "common group." This case-control study included 18 patients with delirium and 34 matched controls in a 63-bed general intensive care unit (ICU). Blood samples were collected from all patients upon ICU admission, on the day when delirium was diagnosed, and on days 3 and 5 following diagnosis. The serum levels of S100B, BDNF, and NSE were determined by enzyme-linked immunosorbent assay. The sedation levels and delirium were assessed using the Richmond Agitation and Sedation Scale and the Confusion Assessment Method for the ICU., Results: The median BDNF, NSE, and S100B concentrations were significantly lower in the dexmedetomidine group than in the common group on the day when delirium was diagnosed and on the third day after delirium was diagnosed. The rate of delirium was significantly lower in the dexmedetomidine group than in the common group. There were clear differences in the BDNF, NSE, and S100B levels between the 2 groups on the fifth day after delirium was diagnosed., Conclusions: Our randomized controlled study suggests that the sedation of polytrauma patients with dexmedetomidine could help reduce the serum BDNF, S100B, and NSE levels, which appear to be associated with the occurrence of delirium in the dexmedetomidine group.

Aim: Long-term survivors (LTS) after glioma recurrence while on bevacizumab (Bev) therapy are rarely reported in the current literature. The purpose of this case series is to confirm the existence of and describe a large cohort of recurrent glioma LTS treated with Bev (Bev-LTS). Patients & methods: We identified Bev-LTS as patients with post-Bev initiation survival times of ≥3 years among 1397 Bev treated recurrent glioma patients. Results: Among 962 grade-IV, 221 grade III, and 214 grade II Bev-treated glioma patients, we identified 28 (2.9%), 14 (6.3%) and 8 (3.7%) Bev-LTS patients, respectively. 45 Bev-LTS patients recurred on Bev, with 36 of those patients continuing therapy.  Conclusion: Our study shows that a small portion of grade-IV, -III, and -II glioma patients can have long-term survival on Bev therapy even after Bev recurrence.

A colorimetric and fluorescent probe ER-ClO was presented in this work to detect cellular hypochlorite with high selectivity and sensitivity. With an organelle targeting unit, ER-ClO was successfully applied in the bio-imaging of exogenous and endogenous hypochlorite in the endoplasmic reticulum in a ratiometric manner.

Previous studies have reported that exposure to lead and cadmium can damage the inner ear receptor, which perceives high-frequency sounds. However, few studies have used the pure-tone average (PTA), including high-frequency ranges, for the estimation of hearing loss caused by lead and cadmium exposure. We estimated hearing loss using the PTA test, in low-frequency, speech frequency, and high-frequency ranges and compared the differences in the results using 3 PTA calculation methods. We analyzed the data of 2,387 participants, between the ages of 19 and 85 years, that were obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) of 2010-2012. A dose-response relationship between hearing loss and heavy metal exposure was observed in the high-frequency method after adjustment for confounding factors. When using the high-frequency PTA, it was found that doubling of the levels of lead and cadmium in the blood was associated with a 1.88- (95% CI 1.11-3.17) and 1.89-fold (95% CI 1.02-3.50) increase in the OR for hearing loss. In the case of the low-frequency and speech frequency PTA, however, there were no significant relationships between hearing loss and the concentrations of lead and cadmium in the blood. The outcomes of the present study suggest that the estimation of hearing loss caused by environmental exposure to lead and cadmium is affected by the frequencies used in the PTA calculation., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

In order to discover new antifungal agrochemicals that could have highly active and novel motifs, thirty-six new 2-acylaminocycloalkylsulfonamides (IV) were synthesized. Their structures were characterized and confirmed by 1 H NMR, 13 C NMR, IR, MS, elemental analysis and X-ray single crystal diffraction. In vitro and in vivo activities against various Botrytis cinerea strains were evaluated. Bioassay results revealed that most of the title compounds exhibited excellent in vitro fungicidal activity, in which compound IV-26 showed the highest activity against sensitive, low-resistant, moderate-resistant and high-resistant strains of B. cinerea compared with the positive fungicide procymidone. Meanwhile in vivo fungicidal activity of compound IV-31 was better than the commercial fungicides procymidone and chesulfamide in greenhouse trial. The structure activity relationship (SAR) was also discussed and the results were of importance to the structural optimization and development of more potent sulfonamides antifungal agents., Competing Interests: The authors declare no competing financial interests.

Background: It is unclear whether simvastatin-ezetimibe could be an alternative therapy to high-intensity statin therapy in high-risk patients. The aim of this study was to compare the clinical outcomes of simvastatin-ezetimibe and high-intensity statin therapy in patients with acute myocardial infarction (AMI), and especially in those with high-risk factor., Methods: A total of 3520 AMI patients in the KAMIR (Korea Acute Myocardial Infarction Registry) were classified into simvastatin-ezetimibe group (n=1249) and high-intensity statin group (n=2271). Multivariate analysis and propensity-score matching analysis were performed. The primary endpoint was major adverse cardiac events (MACE) at 12-months follow-up., Results: In overall AMI patients, MACE occurred in 116 patients (9.3%) in simvastatin-ezetimibe group and 116 patients (5.1%) in high-intensity statin group. The difference in MACE between groups was driven by repeat revascularization (5.9% vs. 2.2%). After propensity matching analysis, simvastatin-ezetimibe was associated with a higher incidence of MACE than high-intensity statin therapy (adjusted hazard ratio: 3.090, 95% confidence interval: 1.715 to 5.566, p<0.001). However, in patients with high-risk factors, such as diabetes, old age, or heart failure, simvastatin-ezetimibe had similar incidence of MACE compared with high-intensity statin therapy in further adjusted analysis., Conclusions: In overall AMI patients, high-intensity statin therapy had better clinical outcomes than simvastatin-ezetimibe. However, in patients with high-risk factor, simvastatin-ezetimibe had comparable clinical outcomes to high-intensity statin therapy. Therefore, simvastatin-ezetimibe could be used as an alternative to high-intensity statin therapy in such patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Paeoniflorin (PAE) is the most abundant compound in Xuebijing injection widely used to treat sepsis. We aimed to investigate effect of PAE on expression of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in a rat model of sepsis. Wistar rats were divided into Normal, Model, and PAE groups (n=20 each). Endotoxin was administrated at 5 mg/ml/kg in Model and PAE rats to establish rat sepsis model. 1 h after endotoxin administration, PAE was administrated at 4 ml/kg in PAE group once per day for 3 days. Routine blood tests and biochemical indexes were assessed, including aspartate aminotransferase (AST) and creatine kinase-MB (CK-MB). The plasma sTREM-1 level was measured using quantitative ELISA. At the end of experiment, the small intestine, liver, kidney and lung were subjected to pathological examinations. A rat model of sepsis-induced multiple organ dysfunction syndrome (MODS) was established successfully with endotoxin administration (5 mg/ml/kg), evidenced by histo-pathological examinations, routine blood tests and biochemical indexes: platelet count decreased and white blood cell count increased (p<0.05), CK-MB and AST increased (p<0.05). PAE treatment significantly reduced the plasma levels of AST, CK-MB, and sTREM-1, compared to Model group (p<0.05). Meanwhile, sepsis-induced damages in the liver, lung, stomach and intestinal mucosa were also markedly ameliorated by PAE treatment. PAE demonstrated a significantly protective effect in a rat model of sepsis by decreasing plasma sTREM-1 level, reducing inflammation, preventing MODS and protecting organ functions., Competing Interests: The authors report no declarations of interest.

Background: Despite common use of second-generation drug-eluting stents in treating patients with coronary artery disease, there is lack of data comparing these stents exclusively in patients with acute myocardial infarction (AMI), especially with metabolic syndrome (MetS), which is highly prevalent in AMI and potential to worsen clinical outcomes. The aim of this study was to compare clinical outcomes of everolimus-eluting stent (EES) and Resolute-zotarolimus-eluting stent (R-ZES) in AMI patients with MetS, in terms of stent-related and patient-related outcomes., Methods: A total of 3942 AMI patients in the KAMIR (Korea Acute Myocardial Infarction Registry) were grouped according to the presence of MetS and stent type: EES (N=1582) and R-ZES (N=255) in MetS (1837). Target lesion failure (TLF) and patient-oriented composite events (POCE) at 1 year were evaluated., Results: In MetS patients, TLF (3.7% vs. 2.7%, p=0.592) and POCE (7.9% vs. 6.7%, p=0.764) were similar between EES and R-ZES. Also in Non-MetS patients, TLF (3.9% vs. 3.1%, p=0.307) and POCE (6.4% vs. 7.3%, p=0.866) were similar between 2 groups. TLF was similar between MetS and Non-MetS patients (3.6% vs. 3.8%), while POCEs (7.7% vs. 6.6%) were higher in MetS. Propensity-score matching analysis showed similar results between stent groups in MetS and Non-MetS. In multivariate analysis, left ventricular ejection fraction and symptom-to-door time were independent predictors of TLF and POCE in MetS patients with AMI., Conclusions: In MetS patients with AMI, EES and R-ZES showed excellent performance and safety. However, patient-oriented composite events were relatively high, suggesting more efforts to improve them., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Introduction: Recent studies have revealed that lung inflammation mediated by CD4+ T cells may contribute to the pathogenesis of acute respiratory distress syndrome (ARDS). The imbalance between CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and T helper (Th)17 cells has been found in a number of different inflammation and autoimmune diseases, while the role of the Th17/Treg balance in ARDS remains largely unknown. The aim of this study was to investigate the Th17/Treg pattern and its impact on disease severity and outcomes in patients with ARDS., Methods: This prospective, observational study enrolled 79 patients who fulfilled the Berlin definition of ARDS and 26 age- and sex-matched healthy controls. Circulation Th17 and Treg cell frequencies were analyzed by flow cytometry, and the expressions of Th17- and Treg-related cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). Acute Physiologic and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and the Lung Injury Score were also calculated at enrollment., Results: Within 24 hours after the onset of ARDS, the changes of peripheral circulating Th17 and Treg cell frequencies gradually increased from mild to severe ARDS. Th17/Treg ratio was positively correlated with APACHE II score, SOFA score, and Lung Injury Score, while negatively correlated with PaO₂/FiO₂. The areas under the receiver operating characteristic (AUC) curves of Th17/Treg ratio for predicting 28-day mortality in ARDS patients was higher than that of APACHE II score, SOFA score, Lung injury score, as well as PaO2/FiO2. Using a Th17/Treg ratio cutoff value of >0.79 to determine 28-day mortality, the sensitivity was 87.5% with 68.1% specificity. Multivariate logistic regression showed Th17/Treg ratio >0.79 (odds ratio = 8.68, P = 0.002) was the independent predictor for 28-day mortality in patients with ARDS. Finally, cumulative survival rates at 28-day follow-up also differed significantly between patients with Th17/Treg ratio >0.79 and ≤0.79 (P <0.001)., Conclusions: The Th17/Treg imbalance favoring a Th17 shift represents a potential therapeutic target to alleviate lung injury and a novel risk indicator in patients with early ARDS.

Background: Despite good treatment, there are residual risks in acute myocardial infarction (AMI) patients, and low level of high-density lipoprotein-cholesterol (HDL) has drawn attention as a possible cause. However, the impact of low HDL on ST-segment-elevation myocardial infarction (STEMI) compared with non-ST-segment-elevation myocardial infarction (NSTEMI) is not clear. Our aim was to evaluate the impact of low HDL on clinical outcomes in patients with STEMI or NSTEMI., Methods: We included 9270 AMI patients undergoing successful percutaneous coronary intervention. They were grouped into STEMI and NSTEMI, and subdivided into two groups according to HDL level sampled in overnight fasting state. Primary end point was in-hospital death. Secondary end point was a composite of major adverse cardiac events (MACE) in hospital survivors during one-year follow-up., Results: In the STEMI population, low HDL group showed significantly higher in-hospital death rate [4.6% vs. 1.4%, hazard ratio (HR): 2.380, 95% confidence interval (CI): 1.143-4.956, p=0.020] than normal HDL group. In NSTEMI population, there was no significant difference between two groups (1.8% vs. 0.9%, HR: 1.231, 95% CI: 0.649-2.335, p=0.525), but in subgroup analysis, very low HDL subgroup showed higher in-hospital mortality rate compared with normal HDL group (4.0% vs. 0.9%, respectively, p=0.009). In 12-month MACE rates, there was no significant difference between two groups in both populations., Conclusions: Low HDL was associated with significantly higher risk of in-hospital mortality in STEMI patients, but not in NSTEMI patients. Thus, more aggressive treatment should be considered in STEMI patients with low HDL., (Copyright © 2014. Published by Elsevier Ltd.)

Background and Objectives: Metabolic syndrome (MetS) is an important risk factor for cardiovascular disease. However, the clinical outcome of acute myocardial infarction (AMI) with MetS has not been well examined. The purpose of this study was to evaluate the clinical outcomes of AMI patients with MetS., Subjects and Methods: We evaluated a total of 6352 AMI patients who had successful percutaneous coronary interventions and could be identified for MetS between 2005 and 2008 at 51 hospitals participating in the Korea Acute Myocardial Infarction Registry. They were divided into 2 groups according to the presence of MetS: the MetS group (n=2493, 39.2%) versus the Non-MetS group (n=3859, 60.8%). In addition, 4049 AMI patients with high levels of low density lipoprotein-cholesterol (LDL-C) (≥100 mg/dL) among them, were divided into the MetS group (n=1561, 38.6%) versus the Non-MetS group (n=2488, 61.4%)., Results: In the overall population, there was no significant difference in 12-month the major adverse cardiac events (MACE) rate between the 2 groups. However, the MetS group showed a significantly higher 12-month MACE rate in the high LDL-C population. Multivariate analysis showed that MetS was an independent prognostic factor for 12-month MACE {hazard ratio (HR) 1.607, 95% confidence interval (CI) 1.027 to 2.513, adjusted p=0.038} and for 12-month target vessel revascularization (HR 1.564, 95% CI 1.092 to 2.240, adjusted p=0.015) in the high LDL-C population., Conclusion: MetS patients with AMI in the overall population showed no significant difference in 12-month clinical outcomes. However, in patients with higher LDL-C ≥100 mg/dL, they showed significantly worse clinical outcome than Non-MetS patients. Therefore, it is important to ascertain the presence of MetS in AMI patients, and more aggressive therapy should be strongly considered for AMI patient with MetS.

Serum procalcitonin (PCT) levels may have predictive value in the prognosis of postoperative sepsis in elderly patients who have undergone colorectal surgery for colorectal cancer in intensive care units (ICUs). A prospective study involving 90 critically ill patients who underwent colorectal surgery for colorectal cancer in ICUs was performed. Twenty-eight patients were diagnosed with sepsis, in accordance with the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria, and these patients were included in the sepsis group. Sixty-two patients, who were without evidence of sepsis, were enrolled in the control group. We measured the serum PCT concentrations preoperatively (immediately before induction of anesthesia), upon arrival in the ICU (ICU day 0), on the morning of the first postoperative day (postoperative day 1), and on the morning of the third postoperative day (postoperative day 3). The C-reactive protein (CRP) index, acute physiology and chronic health evaluation II (APACHE II) score, mechanical duration of ventilation, mortality rate, incidence of multiple organ failure, and usage of continuous renal replacement therapy were evaluated. The area under the curve for the receiver operating characteristic curve (AUC-ROCC) was measured to explore the association between the serum PCT and the prognosis. In the sepsis group, 12/28 patients died (mortality rate 43 %). In the control group, 6/62 patients died (mortality rate 9.7 %). On the first postoperative day, the serum PCT level was dramatically higher in the sepsis group than in the control group (2.71 ± 1.13 vs. 1.37 ± 0.57, P ≤ 0.05). The PCT level on the first postoperative day was distinctly higher than that measured upon arrival in the ICU (2.71 ± 1.13 vs. 1.31 ± 0.58, P ≤ 0.05). In the two groups, the CRP concentrations were both markedly higher on the first postoperative day than upon arrival in the ICU (138.89 ± 45.12 vs. 70.43 ± 23.54 in the sepsis group, and 133.13 ± 44.91 vs. 69.65 ± 24.98 in the control group, P ≤ 0.05). Linear regression analysis was performed. The results suggest that the PCT and APACHE-II scores were not significantly associated. On the first and third postoperative days, the PCT levels were associated with increased odds of sepsis (AUC-ROCC, 95 % confidence interval 0.817-0.973, P = 0.000, and 0.755-0.944, P = 0.000, respectively). The outcomes of patients in the sepsis group were worse than those in the control group. PCT levels appear to be early markers of postoperative sepsis in elderly patients undergoing colorectal surgery for colorectal cancer during the ICU course. These findings could allow for early identification of postoperative septic complications and be used for prognostic evaluation of these patients.

Chronic myeloid leukemia (CML) is a clonal hematologic malignancy characterized by the BCR-ABL protein. BCR-ABL is a constitutively active tyrosine kinase and plays a critical role in the pathogenesis of CML. Imatinib mesylate, a selective tyrosine kinase inhibitor, is effective in CML, but drug resistance and relapse occur. The coiled-coil (CC) domain located in BCR(1-72) mediates BCR-ABL tetramerization, which is essential for the activation of tyrosine kinase and transformation potential of BCR-ABL. CC domain is supposed to be a therapeutic target for CML. We purified a TAT-CC protein competively binding with the endogenous CC domain to reduce BCR-ABL kinase activity. We found that TAT-CC co-located and interacted with BCR-ABL in Ba/F3-p210 and K562 cells. It induced apoptosis and inhibited proliferation in these cells. It increased the sensitivity of these cells to imatinib and reduced the phosphorylation of BCR-ABL, CRKL and STAT5. We confirmed that TAT-CC could attenuate the oncogenicity of Ba/F3-p210 cells and diminish the volume of K562 solid tumor in mice. We conclude targeting the CC may provide a complementary therapy to inhibit BCR-ABL oncogenicity.

Objective: To evaluate the effects of real-time continuous glucose monitoring (RT-CGM) system on oxidative stress and mortality in critically ill patients and to explore the correlation between glucose index, oxidative stress and mortality., Methods: Selected 123 cases of critically ill patients were enrolled in this prospective randomized controlled study. They were randomly divided into the RT-CGM group (n = 61) and blood glucose meter group (GM group, n = 62). The following parameters were compared between the two groups: mean amplitude of glucose excursions (MAGE), hypoglycemia incidence, low blood glucose index (LBGI), high blood glucose index (HBGI), 28-day mortality and plasma level of 8-iso-PGF2α (8-iso) at 48 hours (R2), 72 hours (R3) and 96 hours (R4) after admission to ICU. The correlation between glucose index and plasma level of 8-iso-PGF2α were analyzed. The correlation between glucose index, plasma 8-iso level and 28-day death were analyzed., Results: The parameters of MAGE, hypoglycemia incidence, LBGI and HBGI in the RT-CGM group and the GM group were (3.73 ± 1.09) mmol/L and (4.19 ± 1.11) mmol/L (P = 0.02), 3.28% and 14.52% (P = 0.03), 0.0011 and 0.0119 (P < 0.01) and 0.2258 and 0.3697 (P < 0.01), respectively. The plasma levels of 8-iso at R2, R3, R4 in the RT-CGM group and the GM group were (111.44 ± 16.99) ng/L and (114.03 ± 14.64) ng/L (P = 0.37), (94.53 ± 14.92) ng/L and (110.31 ± 13.42) ng/L (P < 0.01) and (57.84 ± 12.22) ng/L and (84.41 ± 14.16) ng/L (P < 0.01), respectively. The r values between MAGE, LBGI, HBGI and the plasma level of 8-iso were 0.69, 0.71 and 0.67, respectively (all P values < 0.01). Multivariate stepwise regression analysis showed MAGE, LBGI, HBGI entered final models (corrected R2 = 0.61, P < 0.01) with β values of 0.64, 0.65 and 0.6 respectively (all P values < 0.01). The 28-day mortality in the RT-CGM group and the GM group was 9.84% and 30.65% (P < 0.01). The OR values of MAGE, hypoglycemia incidence, LBGI, HBGI and the plasma level of 8-iso for 28-day death were 2.14 (0.98 - 4.35), 3.43 (1.12 - 5.82), 2.67 (1.01 - 5.14), 1.32 (0.24 - 2.96) and 1.89 (0.67 - 3.44), respectively., Conclusion: RT-CGM can optimize the care in critically ill patients by improving hypoglycemia, hyperglycemia, glucose variability and oxidative stress and bring more detailed concern in the process, and to reduce the mortality.

To explore the invasion mechanisms of Conyza canadensis and develop effective control measures, this paper studied the photosynthetic characteristics of the invasive plant and its main associated plants Ixeris chinensis and Commelina communis. The light saturation point and light compensation point of C. canadensis were 1634.00 and 23.84 micromol x m(-2) x s(-1), respectively, which were between those of the two associated plants. The maximum net photosynthetic rate of C. canadensis below light saturation point was 28.12 micromol x m(-2) x s(-1), being much higher than that of the two associated plants. The apparent quantum yield of C. canadensis was 0.06, equal to that of I. chinensis but higher than that of C. communis. The CO2 saturation point and CO2 compensation point of C. canadensis were 834.00 and 23.69 micromol x mol(-1), respectively. The maximum net photosynthetic rate of C. canadensis below CO2 saturation point was 31.97 micromol x m(-2) x s(-1), which was between that of the two associated species. The carboxylation efficiency of C. canadensis was 0.078, being higher than that of the two associated species. The variations of photosynthetically active radiation and CO2 concentration had little effects on the stomatal conductance and transpiration rate of the three plants, but significantly affected their water use efficiency. C. canadensis had higher photosynthetic rate and material accumulation capability, and its high productivity could be one of the important factors for its successful invasion.

Background: With the objective of exploring the fungicidal activity of 2-oxocyclohexylsulfonamides (2), a series of novel 2-amino-6-oxocyclohexenylsulfonamides (6 to 23) were synthesised, and their fungicidal activities against Botrytis cinerea Pers. were evaluated in vitro and in vivo., Results: The compounds were characterised by IR, 1H NMR and elemental analysis. Bioassay results of mycelial growth showed that compounds 6 to 23 had a moderate antifungal activity against B. cinerea. N-(2-methylphenyl)-2-(2-methylphenylamino)-4,4-dimethyl-6-oxocyclohexenylsulfonamide (13) and N-(2-chlorophenyl)-2-(2-chlorophenylamino)-6-oxocyclohexenylsulfonamide (21) showed best antifungal activities, with EC50 values of 8.05 and 10.56 µg mL(-1) respectively. Commercial fungicide procymidone provided an EC50 value of 0.63 µg mL(-1) . The conidial germination assay showed that most of compounds 6 to 23 possessed excellent inhibition of spore germination and germ-tube elongation of conidia of B. cinerea. For in vivo control of B. cinerea colonising cucumber leaves, the compound N-cyclohexyl-2-(cyclohexylamino)-4,4-dimethyl-6-oxocyclohexenylsulfonamide (19) showed a better control effect than the commercial fungicide procymidone., Conclusion: The present work demonstrated that 2-amino-6-oxocyclohexenylsulfonamides can be used as possible new lead compounds for further developing novel fungicides against B. cinerea., (Copyright © 2011 Society of Chemical Industry.)

Objective: To explore the effects of continuous renal replacement therapy (CRRT) on serum cytokines and prognosis in multiple organ dysfunction syndrome (MODS) patients based on different therapeutic opportunities., Methods: A total of 34 MODS patients in the treatment of CRRT after admission to ICU of our hospital between July 2008 and October 2010 were recruited. Based on the time interval from the onset of MODS to the initiation of CRRT, the patients were stratified into early group (0 - 3 days, n = 16) and late group (4 - 10 days, n = 18). Both groups of MODS patients received conventional treatment in addition to 72 hours of high-volume hemofiltration (HVHF). The serum levels of such inflammatory mediators as interleukin (IL)-1β, interleukin-1 receptor antagonist (IL-1Ra), IL-6, tumor necrosis factor (TNF)-α, soluble tumor necrosis factor receptor1 (sTNFR1) and IL-10 were detected by enzyme linked immunosorbent assay (ELISA) before CRRT (0 h) and 6, 12, 18, 24, 48 and 72 h during the treatment of CRRT. Dynamic APACHEII scores were also evaluated., Results: (1) The early group had lower serum levels of IL-1β, IL-6, IL-10 and higher IL-1Ra, L-1Ra/IL-1β ratio at 72 h than those of 0 h (P < 0.05). And the late group had a declining serum level of IL-1β, IL-6, TNF-α and IL-10 and a rising ratio of IL-1Ra and IL-1Ra/IL-1β during the first 24 h (P < 0.05). As compared with the late group, the early group had a lower level of IL-10 [(25 ± 12) vs (51 ± 33) ng/L] and higher ratios of IL-1Ra and IL-1Ra/IL-1β at 72 h [(1382 ± 899 vs (683 ± 188) ng/L, (54 ± 10) vs (23 ± 6)] (both P < 0.05). (2) The early group had a lower APACHEIIscore than the late group at 0 h (P < 0.05). APACHEII score at 72 h was significantly lower than 0 h in the early group. And there was no obvious change in the late group. There was no statistical difference in the numbers of MODS patients with dysfunctional organs number ≥ 4 at 0 h in both groups. The number of MODS patients with dysfunctional organs number ≥ 4 at 72 h was lower than 0 h in the early group (P < 0.05). And there was no statistical difference in the late group., Conclusion: Regulating the ratio of anti-inflammatory/pro-inflammatory mediators is critical in the immunomodulation of CRRT. And CRRT may provide more clinical benefits in the early phase (0 - 3 days) of MODS.

To explore new potential fungicides, a series of novel compounds, including 11 2-oxocycloalkylsulfonamide (3) and 21 2-hydroxycycloalkylsulfonamide (4) derivatives, were synthesized and their structures were confirmed by (1)H nuclear magnetic resonance (NMR), infrared (IR), and elemental analysis. The results of the bioassay showed that the compounds 3 and 4 possessed excellent fungicidal activity against Botrytis cinerea Pers. both in vitro and in vivo. The fungicidal activity of the compounds with 7- or 8-membered rings is better than those with 5-, 6-, or 12-membered rings. According to the results of the mycelium growth rate test, the EC50 values of the compounds 3C, 4C, 3D, and 4D were 0.80, 0.85, 1.22, and 1.09 μg/mL, respectively, and similar to or better than commercial fungicide procymidone. The bioassay results of spore germination indicated that most of the compounds exhibited obvious inhibitory effects against B. cinerea and the inhibition rates of 2-oxocycloalkylsulfonamides were higher than 2-hydroxycycloalkylsulfonamides, among them. The EC50 values of compounds 3A, 3B17, 3E, and 4A were 4.21, 4.21 3.24, and 5.29 μg/mL, respectively. Those compounds containing 5- or 6-membered rings showed better activity than those containing 7-, 8-, or 12-membered rings. Furthermore, the results of the pot culture test showed that almost all of the compounds had effective control activity in vivo and 2-hydroxycycloalkylsulfonamides were obviously superior to 2-oxocycloalkylsulfonamides. The compounds 3E, 4C and 4D presented higher control efficacy than procymidone and pyrimethanil against gray mold disease on cucumber plants.

Objective: To investigate the changes of interleukin (IL)-6 serum level in patients with acute respiratory distress syndrome (ARDS) and the effects of continuous renal replacement therapy (CRRT) on IL-6 level and its clinical significance., Methods: Forty ARDS patients were randomly divided into 2 equal groups: Group A undergoing conventional treatment and Group B receiving conventional treatment plus CRRT at onset of ARDS. Serum IL-6 level was measured by enzyme linked immunosorbent assay (ELISA) at the onset (0 h) and 12, 24, 48, and 72 hours later. Dynamic APACHEII score was also evaluated at the time points of 0, 24, 48, and 72 h. The incidence of ventilator-associated pneumonia (VAP), intensive care unit (ICU) mortality rate, duration of total mechanical ventilation, and ICU stay were assessed. Twenty-five healthy examinees were used as controls., Results: The serum IL-6 level of the whole ARDS patients was significantly higher then that of the normal controls (P < 0.01), and the serum IL-6 level of the ARDS patients who died was significantly higher than that of the ARDS patients who survived (P < 0.01). The IL-6 serum level was correlated well with the APACHEIIscore either in the survival subgroup or the non-survival subgroup (for the former: r = 0.560 P = 0.008, and for the latter: r = 0.518 P = 0.023). Group B, contrary to Group A, had persistently decreased serum IL-6 levels and APACHEII scores at the onset and during the progression of ARDS (all P < 0.05). The incidence of VAP in Group B was 45%, significantly lower than that in Group A (80%, P = 0.022) while the ICU mortality rate didn't differ between the two groups (40% vs 55%, P = 0.342). The duration of total mechanical ventilation and ICU stay of the Group B patients who underwent early CRRT were (12 +/- 5) days and (16 +/- 5) days respectively, both significantly shorter than those of Group A patients [(16 +/- 5) days, P = 0.027 and (19 +/- 5) days, P = 0.030]., Conclusion: The elevated serum IL-6 level in ARDS patients seems to be correlated well with the severity of lung injury, and appears to be a good marker to judge the prognosis of the disease combined with APACHEII score. In the early phase of ARDS, CRRT can decrease the high serum level of IL-6, shorten the duration of total mechanical ventilation and ICU stay, and decrease the incidence of VAP. Removal of the circulating proinflammatory cytokines by CRRT may be one of the most vital mechanisms to treat ARDS.

We investigated the in vitro effect of modified Je-Ho-Tang (MJHT) hot-water extract on platelet aggregation and activation induced by agonists in human whole blood, and on platelet adhesion to a collagen-coated surface under flow shear stress conditions. MJHT extract potently inhibited the collagen-induced platelet aggregation in human whole blood in a dose-dependent manner, with a half-maximal inhibitory dose (IC(50)) value of 526 microg/mL. We accessed several markers of platelet activation using receptor expression on platelet membranes, including GPIIb/IIIa-like expression (PAC-1) and P-selectin (CD62); we monitored the intracellular calcium mobilization response by flow cytometry in healthy subjects. A significant decrease in PAC-1 (P=0.002), CD62 (P=0.002), and intracellular calcium mobilization (P<0.001) were seen in the presence of MJHT extract. In addition, we have used image analysis to study human platelet adhesion to collagen under physiologic flow conditions in a perfusion chamber. MJHT extract markedly decreased platelet adhesion to the collagen-coated surface. These results show that MJHT has potent anti-platelet activity.

Geranium (Pelargonium inquinans Ait) leaves were extracted with 80% MeOH, and partitioned into n-hexane, ethyl acetate, BuOH and H2O to isolate the anticoagulant principles. The EtOAc fraction was found to be the most active, and was further purified using silica and octadecylsilane column chromatography employing a bioassay-guided fractionation method. The active compound was isolated and identified as 1,2,3,4,6-pentagalloyl-beta-D-glucopyranose (PGG) (compound I). The isolated anticoagulant significantly prolonged the activated partial thrombin time (APTT) and thrombin time (TT) using normal human plasma. One microgram of 1,2,3,4,6-pentagalloyl-beta-D-glucopyranose showed 0.063 heparin units in the APTT and 2.73 heparin units in the TT for anti-thrombosis. This is the first report of the isolation of PGG from geranium plants.