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The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Acidic postconditioning by transient CO 2 inhalation applied within minutes after reperfusion has neuroprotective effects in the acute phase of stroke. However, the effects of delayed chronic acidic postconditioning (DCAPC) initiated during the subacute phase of stroke or other acute brain injuries are unknown. Mice received daily DCAPC by inhaling 5%/10%/20% CO 2 for various durations (three cycles of 10- or 20-min CO 2 inhalation/10-min break) at days 3-7, 7-21, or 3-21 after photothrombotic stroke. Grid-walk, cylinder, and gait tests were used to assess motor function. DCAPC with all CO 2 concentrations significantly promoted motor functional recovery, even when DCAPC was delayed for 3-7 days. DCAPC enhanced the puncta density of GAP-43 (a marker of axon growth and regeneration) and synaptophysin (a marker of synaptogenesis) and reduced the amoeboid microglia number, glial scar thickness and mRNA expression of CD16 and CD32 (markers of proinflammatory M1 microglia) compared with those of the stroke group. Cerebral blood flow (CBF) increased in response to DCAPC. Furthermore, the mRNA expression of TDAG8 (a proton-activated G-protein-coupled receptor) was increased during the subacute phase of stroke, while DCAPC effects were blocked by systemic knockout of TDAG8, except for those on CBF. DCAPC reproduced the benefits by re-expressing TDAG8 in the peri-infarct cortex of TDAG8-/- mice infected with HBAAV2/9-CMV-TDAG8-3flag-ZsGreen. Taken together, we first showed that DCAPC promoted functional recovery and brain tissue repair after stroke with a wide therapeutic time window of at least 7 days after stroke. Brain-derived TDAG8 is a direct target of DCAPC that induces neuroreparative effects., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The involvement of quality of life as the UNAIDS fourth 90 target to monitor the global HIV response highlighted the development of patient-reported outcome (PRO) measures to help address the holistic needs of people living with HIV/AIDS (PLWHA) beyond viral suppression. This study developed and tested preliminary measurement properties of a new patient-reported outcome (PROHIV-OLD) measure designed specifically to capture influences of HIV on patients aged 50 and older in China., Methods: Ninety-three older people living with HIV/AIDS (PLWHA) were interviewed to solicit items and two rounds of patient cognitive interviews were conducted to modify the content and wording of the initial items. A validation study was then conducted to refine the initial instrument and evaluate measurement properties. Patients were recruited between February 2021 and November 2021, and followed six months later after the first investigation. Classical test theory (CTT) and item response theory (IRT) were used to select items using the baseline data. The follow-up data were used to evaluate the measurement properties of the final instrument., Results: A total of 600 patients were recruited at the baseline. Of the 485 patients who completed the follow-up investigation, 483 were included in the validation sample. The final scale of PROHIV-OLD contained 25 items describing five dimensions (physical symptoms, mental status, illness perception, family relationship, and treatment). All the PROHIV-OLD dimensions had satisfactory reliability with Cronbach's alpha coefficient, McDonald's ω, and composite reliability of each dimension being all higher than 0.85. Most dimensions met the test-retest reliability standard except for the physical symptoms dimension (ICC = 0.64). Confirmatory factor analysis supported the structural validity of the final scale, and the model fit index satisfied the criterion. The correlations between dimensions of PROHIV-OLD and MOS-HIV met hypotheses in general. Significant differences on scores of the PROHIV-OLD were found between demographic and clinical subgroups, supporting known-groups validity., Conclusions: The PROHIV-OLD was found to have good feasibility, reliability and validity for evaluating health outcome of Chinese older PLWHA. Other measurement properties such as responsiveness and interpretability will be further examined., (© 2024. The Author(s).)

Spin polarization of two-dimensional electron gas (2DEG) at the interface of EuTiO 3 /SrTiO 3 (STO) heterostructures has been theoretical predicted and experimentally observed via x-ray magnetic circular dichroism and polarized x-ray absorption spectroscopy, which, however, is lack of magnetotransport evidence. Here, we report the fabrication of high-quality EuTiO 3 /STO heterostructures by depositing antiferromagnetic insulating EuTiO 3 thin films onto STO substrates. Shubnikov-de Haas oscillation, Hall, and magnetoresistance (MR) measurements show that the interface is not only highly conducting, with electron mobility up to5.5×103cm 2 V -1 s -1 at 1.8 K, but also shows low-field hysteretic MR effects. MR of ∼9% is observed at 1.8 K and 20 Oe, which is one order of magnitude higher than those observed in other spin-polarized 2DEG oxide systems. Moreover, the heterostructures show ferromagnetic hysteresis loops. These results demonstrate that the high-mobility 2DEG is spin polarized, whose origin is attributed to the interfacial Ti 3+ -3 d states due to oxygen deficiency and the exchange interactions between interfacial Eu spins and itinerant Ti-3 d electrons., (© 2023 IOP Publishing Ltd.)

The field of Chinese medical natural language processing faces a significant challenge in training accurate entity recognition models due to the limited availability of high-quality labeled data. In response, we propose a joint training model, MCBERT-GCN-CRF, which achieves high performance in identifying medical-related entities in Chinese electronic medical records. Additionally, we introduce CM-NER, a 5-step framework that effectively mitigates the effects of noise in weakly labeled data and establishes a principled connection between supervised and weakly supervised named entity recognition. We demonstrate significant improvements in recall rate and accuracy. Our approach outperforms traditional fully supervised pre-training models and other state-of-the-art methods by suppressing noise in weakly labeled data. Our proposed framework achieves an F1 score of 86.29% on the CCKS-2019 dataset, significantly higher than pre-trained model baselines ranging from 74.17 to 83.06%, and higher than the top-performing named entity recognition supervised learning models in the CCKS-2019 competition. Our results demonstrate the effectiveness of our proposed framework and highlight the potential of leveraging unlabeled data to train accurate models for named entity recognition in Chinese medical natural language processing. This research has significant implications for advancing natural language processing techniques in the medical domain and improving patient care., (© 2023. International Federation for Medical and Biological Engineering.)

Pregnane X receptor (PXR) is a xenobiotic receptor that can be activated by numerous chemicals including endogenous hormones, dietary steroids, pharmaceutical agents, and environmental chemicals. PXR has been established to function as a xenobiotic sensor to coordinately regulate xenobiotic metabolism by regulating the expression of many enzymes and transporters required for xenobiotic metabolism. Recent studies have implicated a potentially important role for PXR in obesity and metabolic disease beyond xenobiotic metabolism, but how PXR action in different tissues or cell types contributes to obesity and metabolic disorders remains elusive. To investigate the role of adipocyte PXR in obesity, we generated a novel adipocyte-specific PXR deficient mouse model (PXR ΔAd ). Notably, we found that loss of adipocyte PXR did not affect food intake, energy expenditure, and obesity in high-fat diet-fed male mice. PXR ΔAd mice also had similar obesity-associated metabolic disorders including insulin resistance and hepatic steatosis as control littermates. PXR deficiency in adipocytes did not affect expression of key adipose genes in PXR ΔAd mice. Our findings suggest that adipocyte PXR signaling may be dispensable in diet-induced obesity and metabolic disorders in mice. Further studies are needed to understand the role of PXR signaling in obesity and metabolic disorders in the future. SIGNIFICANCE STATEMENT: The authors demonstrate that deficiency of adipocyte pregnane X receptor (PXR) does not affect diet-induced obesity or metabolic disorders in mice and infers that adipocyte PXR signaling may not play a key role in diet-induced obesity. More studies are needed to understand the tissue-specific role of PXR in obesity., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Cross-lingual entity alignment in knowledge graphs is a crucial task in knowledge fusion. This task involves learning low-dimensional embeddings for nodes in different knowledge graphs and identifying equivalent entities across them by measuring the distances between their representation vectors. Existing alignment models use neural network modules and the nearest neighbors algorithm to find suitable entity pairs. However, these models often ignore the importance of local structural features of entities during the alignment stage, which may lead to reduced matching accuracy. Specifically, nodes that are poorly represented may not benefit from their surrounding context. In this article, we propose a novel alignment model called SSR, which leverages the node embedding algorithm in graphs to select candidate entities and then rearranges them by local structural similarity in the source and target knowledge graphs. Our approach improves the performance of existing approaches and is compatible with them. We demonstrate the effectiveness of our approach on the DBP15k dataset, showing that it outperforms existing methods while requiring less time.

Rationale: Giltelman syndrome (GS) is an autosomal recessive infectious disease, which is caused by the mutation of SLC12A3 gene encoding thiazide diuretic sensitive sodium chloride cotransporter located in the distal convoluted tubule of the kidney., Patient Concerns: A 7-year-old and 3-month-old male patient has poor appetite, slow growth in height and body weight since the age of 3, body weight: 16 kg (-3 standard deviation), height: 110 cm (-3 standard deviation), normal exercise ability and intelligence. One year ago, he was diagnosed with hypokalemia. After potassium supplement treatment, the blood potassium returned to normal. The patient developed abdominal pain, vomiting, limb weakness, and tetany 1 day before admission., Diagnoses: After admission examination, the patient was found to have hypokalemia (2.27-2.88 mmol/L), hypomagnesemia (0.47 mmol/L), hypophosphatemia (1.17 mmol/L), hypocalcemia (1.06 mmol/24 hours), and metabolic alkalosis (PH 7.60). The blood pressure is normal, and the concentration of aldosterone is 791.63 pg/mL. The adrenocorticotropic hormone and cortisol detected at 8 am are 4.95 pmol/L and 275.09 nmol/L, respectively. Twenty-four hours of urine potassium is 32.52 mmol. Gene sequencing results showed 2 pathogenic variants in the GS-related SLC12A3 gene, which are related to the phenotype of the subject., Interventions: After admission, the patients were given potassium and magnesium supplements, as well as oral spironolactone. The symptoms of limb weakness and tetany were significantly relieved. After discharge, the patients continued to maintain treatment to keep the blood potassium at more than 3.0 mmol/L, and the blood magnesium at more than 0.6 mmol/L., Outcomes: Follow-up at 1 month after discharge, in the patient's self-description, he had no symptoms such as limb weakness and tetany, and his height was increased by 1 cm and the body weight increased by 1.5 kg., Lessons: For patients with hypokalemia, hypomagnesemia, and metabolic alkalosis, the possibility of GS should be given priority. After the diagnosed by gene sequencing of SLC12A3 gene, potassium and magnesium supplementation could significantly improve symptoms., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Mycoplasma pneumoniae is one of the most important pathogens causing community acquired pneumonia in children, and the pathogenic mechanism of M. pneumoniae infection is complex. Azithromycin is an effective agent for treating the acquired lower respiratory tract infection and urogenital tract infection with slight adverse reactions. This study aimed to compare the intestinal microflora before (PP1) and after azithromycin intervention (PP2) in children with pneumonia caused by M. pneumoniae, combined with body fluid biochemical analysis to determine the intestinal flora affecting the progress of the disease. Fifteen children diagnosed with M. pneumoniae pneumonia were recruited. The fecal samples and clinical biochemical data were collected. 16S rRNA gene amplicon sequencing and bioinformatics analysis were conducted by the Beijing Genomics Institute. The operational taxonomic unit abundance analysis showed significant differences between the two groups. The species richness analysis showed differences in class, family, genus, order, species, and phylum. The abundance of Haemophilus, Pasteurellales, and Pasteurellaceae was found to be significantly higher in the PP1 group. The Pearson correlation analysis showed that the microbes strongly correlated with the clinical features. 16S rRNA gene sequencing data revealed altered composition of gut microbiota in children with M. pneumoniae pneumonia treated with azithromycin. The altered expression of microbes correlated with clinical features, which might help diagnose and treat the disease.

High-quality Mn 2- x Cr x Sb ( x = 0.01, 0.04, and 0.1) epitaxial thin films were grown on SrTiO 3 (STO) (001) single-crystal substrates using molecular beam epitaxy. Magnetotransport and magnetic measurements reveal that the x = 0.01 sample undergoes a quasi-ferrimagnetic (I) [Q-FIM(I)]-to-ferrimagnetic (II) [FIM(II)] spin reorientation (SR) transition and a giant magnetoresistance (MR) associated first-order ferrimagnetic(II)-to-antiferromagnetic (AFM) phase transition upon cooling, resulting in the AFM ground state with a weak in-plane net moment. Upon increasing the doping level from x = 0.01 to 0.1, both the SR transition and the first-order magnetic transition are suppressed. For x = 0.1, the former transition is suppressed, leaving only the Q-FIM(I)-to-AFM transition within the whole temperature region. T AFM-FIM shows almost similar changes upon the application of either in-plane or out-of-plane magnetic fields. T AFM-FIM values of the x = 0.01 and 0.04 samples are much higher than those of the Mn 2- x Cr x Sb bulk with similar doping levels, which can be understood by the clamping effect from STO substrates. For each thin-film sample, the MR effect is observed near T AFM-FIM and disappears in the high temperature Q-FIM(I) phase and low temperature AFM phase, indicating that MR is related to the spin-dependent electron scattering during the first-order magnetic phase transition. Based on the magnetotransport and magnetic data, a magnetic phase diagram is established for the Mn 2- x Cr x Sb films in the low doping level region.

Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract, with the annual incidence and mortality increasing consistently. Oxaliplatin-based chemotherapy is a preferred therapeutic regimen for patients with advanced CRC. However, most patients will inevitably develop resistance to oxaliplatin. Many studies have reported that non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs, are extensively involved in cancer progression. Moreover, emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation, and by epigenetic modification. In this review, we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin. Furthermore, we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy. This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs., Competing Interests: Conflict-of-interest statement: All authors declare that we have no other real or potential conflict of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The aim of this study is to assess the impacts of urban green space on depressive symptoms among Chinese urban residents aged 45 and older. In total, 7397 urban respondents were included in this study. Each respondent participated in the China Health and Retirement Longitudinal Study Wave 3 (2015). Environmental-level variables were retrieved from the National Bureau of Statistics database. Both unadjusted and adjusted methods were used in the multilevel regression analysis. Almost one-third of the sample population suffered from depressive symptoms (31.20%). The multilevel logistic regression model showed that green coverage ratio of city-built districts is negatively associated with the prevalence of depressive symptoms among urban mid-aged (OR = 0.79, p < 0.05) and elderly (OR = 0.75, p < 0.05) residents, and the public recreational green space helps to reduce elderly people's depressive symptoms (OR = 0.77, p < 0.05). This study adds insights about the impact of green space and other environmental factors on depressive symptoms among mid-aged and elderly urban dwellers. It is important to provide enough and accessible overall urban green spaces; additionally, attention should also be paid to specific green space forms such as public recreational green space.

Schools are an important food environment to cultivate and promote healthy food choices and practices among children and adolescents. The aim of the present study was to assess the type and quality of food and beverages sold in school canteens in public primary and secondary schools in Kelantan, Malaysia. Eligible schools were randomly selected from the list of all schools and detailed information of all food and beverage items sold in the school canteens were collected during school days. Food and beverages were classified based on food groups derived from the Malaysian Food Dietary Guideline and the Recommended Foods for Healthy Cafeteria Guideline. An assessment of the traffic-light nutrition food-labelling system of the total sugar content in all pre-packaged foods was also undertaken. A total of 568 food items were identified, with secondary school canteens selling a greater proportion of food items than the primary schools (55.5% vs. 44.5%). In terms of the main food groups, grains and cereal products represented the largest food group served (33-36%), followed by beverages (21-25%) and confectionary and sweet foods (12-13%). In contrast, the vegetable and fruit group represented the smallest proportion of food items sold (1-3%). Comparisons between primary and secondary schools showed a similar trend and pattern of food types and quality of foods sold, except for animal-based foods. A greater percentage of food items in this category was found among secondary schools (12.1%) versus primary schools (6.7%). When total sugar content of all pre-packaged foods was quantified based on the traffic-light nutrition-labelling system, almost one-third of foods and beverages were classified as high (29.1%). Confectionary (19.1%) and flavoured milk and fruit drinks (10.0%) both exceeded the recommended sugar levels of >22.5 g per 100 g and >11.25 mL per 100 m L, respectively. Only one of these packaged foods and beverages (0.9%) was classified as a healthy food choice. About a quarter of the food items available in school canteens were classified as prohibited based on a new revised list of prohibited food and beverage items. These findings indicate that, despite the Guidelines, a large number of unhealthy food items are being sold in school canteens. Hence, interventions such as sustainable healthy school canteen menus should be implemented to promote healthy food choices amongst school-aged children.

Rationale and Objectives: The purpose of this study was to investigate the role of computed tomography (CT) radiomics for the prediction of the human epidermal growth factor 2 (HER2) status in patients with gastric cancer., Methods: One hundred and thirty two consecutive patients with advanced gastric cancer undergoing radical gastrectomy were retrospectively reviewed. All patients received preoperative contrast CT examination, and immunohistochemistry results of their HER2 status were available. All the subjects were randomly divided into a training cohort (n = 90) and a test cohort (n = 42). Arterial phase (AP) and portal phase (PP) contrast CT images were retrieved for tumor segmentation and feature extraction. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to evaluate the performance of the radiomics classifiers., Results: Among the 132 patients, a total of 99 patients were HER2 negative, and the remaining 33 patients were border line or positive. The AP radiomics model could distinguish HER2-negative cases with an AUC of 0.756 (95% confidence interval [CI]: 0.656-0.840) in the training cohort, which was confirmed in the test cohort with AUC of 0.830 (95% CI: 0.678-0.930). The PP radiomics model showed AUCs of 0.715 (95% CI: 0.612-0.804) and 0.718 (95% CI: 0.554-0.849) in the training and test cohort for distinction of negative HER2 cases, respectively., Conclusion: Radiomics models based on standard-of-care CT images hold promise for distinguishing HER2-negative gastric cancer., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: To compare clinical effect of cannulated screw and bone plate for the treatment of humeral fracture of greater tuberosity., Methods: From January 2010 to January 2020, clinical trial literatures on the treatment of humeral tuberosity fractures with cannulated screw and bone plate were searched by PubMed, EMbase, Cochrane Library, Wanfang, CNKI, CBM Database, VIP Database and other databases. Independent literature screening, quality evaluation, and data extraction were performed according to inclusion and exclusion criteria. Revman5.2 software was used to perform Meta analysis., Results: Totally 5 clinical randomized controlled trials and 12 cohort studies were selected, including 1 068 patientsin which 559 patients were treated by cannulated screw internal fixation and 509 patients treated by bone plate internal fixation. Meta analysis resluts showed that there were satistical differences in operation time[MD=-23.03, 95% CI(-29.69, -16.36), P <0.000 1], blood loss[MD=-36.39, 95% CI(-53.73, -19.04), P <0.000 1], hospital stay[MD=-1.86, 95%CI(-3.09, -0.64), P =0.003], fracture healing time [MD=-2.23, 95% CI (-4.27, -0.18), P =0.03], postoperative incidence of infection [ OR =0.17, 95%CI (0.03, 0.97), P =0.05], failure rate of internal fixation [ OR =3.56, 95% CI (1.29, 9.81), P =0.01] bwteen two groups. While there were no differences in postoperative visual analogue scale (VAS)[MD=-1.34, 95% CI (-2.77, 0.09), P =0.07], American Shoulder and Elbow Surgeons(ASES)[MD=0.26, 95% CI(-6.43, 6.96), P =0.94], Constant shoulder score [MD=-4.05, 95% CI(-8.51, 0.42), P =0.08], excellent rate of Constant shoulder score[MD=-1.30, 95% CI(0.46, 3.72), P =0.62], excellent rate of Neer shoulder joint score[ OR =2.04, 95% CI(0.97, 4.28), P =0.06], total complication rate[ OR =1.50, 95% CI (0.42, 5.35), P =0.53], incidence of postoperative pain[ OR =0.74, 95% CI(0.04, 14.49), P =0.84] and incidence of postoperative acromion syndrome [ OR =0.88, 95% CI (0.02, 40.63), P =0.95] between two groups., Conclusion: Compared with bone plate, cannulated screw for the treatment of humeral fracture of greater tuberosity has advantages of shorter opertaion time, less blood loss, shorter hospital stay, lower incidence rate of postopertaive infection, and more benefit for fracture healing.

Accumulating evidence suggests that chronic metformin posttreatment offers potent neuroreparative effects against acute brain injury. However, in previous studies, metformin was not initially administered beyond 24 h postinjury, and the effects of delayed metformin treatment in traumatic brain injury (TBI) and other types of acute brain injury and the related mechanisms are unclear. To test this, male C57BL/6 mice received once daily metformin treatment (20, 50 or 100 mg/kg/d, i.p.) at day 1-14, day 1-2, day 1-10, day 3-10, day 5-12 or day 5-28 after cryogenic TBI (cTBI). The results showed that 100 mg/kg/d metformin administered at day 1-14 postinjury significantly promoted motor functional recovery in the beam walking and gait tests and reduced the infarct volume. Metformin (100 mg/kg/d) administered at day 1-10 or day 3-10 but not day 1-2 or day 5-12 after cTBI significantly improved motor functional outcomes at day 7 and 14, and reduced the infarct volume at day 14. Interestingly, the therapeutic time window was further expanded when the duration of metformin treatment starting at day 5 postinjury was extended to 2 weeks. Furthermore, compared with cTBI, the administration of metformin at day 3-10 or day 5-28 after cTBI significantly elevated the expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and growth associated protein 43 (an axonal regeneration marker) and the number of vascular branch points and decreased the area of glial scar and the number of amoeboid microglia in the peri-infarct area at day 14 or 28 postinjury. The above beneficial effects of metformin were blocked by the intracerebroventricular injection of the AMPK inhibitor compound C (40 μg/mouse/d). Our data provide the first evidence that metformin has a wide therapeutic time window for at least 5 days after cTBI, during which it can improve functional recovery by promoting tissue repair and inhibiting glial scar formation and microglial activation in a central AMPK-dependent manner., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A fully automated and accurate assay of rare cell phenotypes in densely-packed fluorescently-labeled liquid biopsy images remains elusive. Methods: Employing a hybrid artificial intelligence (AI) paradigm that combines traditional rule-based morphological manipulations with modern statistical machine learning, we deployed a next generation software, ALICE (Automated Liquid Biopsy Cell Enumerator) to identify and enumerate minute amounts of tumor cell phenotypes bestrewed in massive populations of leukocytes. As a code designed for futurity, ALICE is armed with internet of things (IOT) connectivity to promote pedagogy and continuing education and also, an advanced cybersecurity system to safeguard against digital attacks from malicious data tampering. Results: By combining robust principal component analysis, random forest classifier and cubic support vector machine, ALICE was able to detect synthetic, anomalous and tampered input images with an average recall and precision of 0.840 and 0.752, respectively. In terms of phenotyping enumeration, ALICE was able to enumerate various circulating tumor cell (CTC) phenotypes with a reliability ranging from 0.725 (substantial agreement) to 0.961 (almost perfect) as compared to human analysts. Further, two subpopulations of circulating hybrid cells (CHCs) were serendipitously discovered and labeled as CHC-1 (DAPI+/CD45+/E-cadherin+/vimentin-) and CHC-2 (DAPI+ /CD45+/E-cadherin+/vimentin+) in the peripheral blood of pancreatic cancer patients. CHC-1 was found to correlate with nodal staging and was able to classify lymph node metastasis with a sensitivity of 0.615 (95% CI: 0.374-0.898) and specificity of 1.000 (95% CI: 1.000-1.000). Conclusion: This study presented a machine-learning-augmented rule-based hybrid AI algorithm with enhanced cybersecurity and connectivity for the automatic and flexibly-adapting enumeration of cellular liquid biopsies. ALICE has the potential to be used in a clinical setting for an accurate and reliable enumeration of CTC phenotypes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Rationale: Natural products have been great sources for drug discovery. However, the structures of natural products are diverse and difficult to elucidate. Cordyceps militaris is a parasitic fungus which usually grows on host insects. The metabolites of C. militaris have been reported to act as chemotherapeutic agents. In this study, we aimed for the structural elucidation of specialized metabolites derived from C. militaris, and the metabolic impact in leukemia cells., Methods: We describe a liquid chromatography data-dependent mass spectrometric platform combining tandem mass analysis and molecular networking. Leukemia cells treated with C. militaris extract and control groups were visualized in terms of their metabolic profiles using Global Natural Product Social (GNPS) molecular networking. By this method, we were able to elucidate the structures of metabolites from medicinal fungus extracts and cancer cells and then to recognize their changes in a semi-quantitative manner., Results: Using C. militaris and leukemia cells as examples, we found that approximately 100 new ion species were present in the treated leukemia cells, suggesting a highly altered metabolic profile. Specifically, based on the tandem mass spectral similarity, we proposed that cordycepin, a key fungus-derived therapeutic agent known for its antitumor activity, was transformed into its methylthio form in leukemia cells., Conclusions: The platform described provides an ability to investigate complex molecular interactions of natural products in mammalian cells. By incorporating tandem mass spectrometry and molecular networking, we were able to reveal the chemical modification of crude bioactive compounds, for example potential bioactive compounds which might be modified from cordycepin. We envision that such a mass spectrometry (MS)-based workflow, combined with other metabolomics platforms, would enable much wider applicability to cell biology and be of great potential to pharmacological study as well as drug discovery., (© 2019 John Wiley & Sons, Ltd.)

Objective: To investigate the risk factors for cow's milk protein allergy (CMPA) among infants through a multicenter clinical study., Methods: A total of 1 829 infants, aged 1-12 months, who attended the outpatient service of the pediatric department in six hospitals in Shenzhen, China from June 2016 to May 2017 were enrolled as subjects. A questionnaire survey was performed to screen out suspected cases of CMPA. Food avoidance and oral food challenge tests were used to make a confirmed diagnosis of CMPA CMPA. A multivariate logistic regression analysis was used to investigate the risk factors for CMPA., Results: Among the 1 829 infants, 82 (4.48%) were diagnosed with CMPA. The multivariate logistic regression analysis showed that maternal food allergy (OR=4.91, 95%CI: 2.24-10.76, P<0.05), antibiotic exposure during pregnancy (OR=3.18, 95%CI: 1.32-7.65, P<0.05), and the introduction of complementary food at an age of <4 months (OR=3.55, 95%CI: 1.52-8.27, P<0.05) were risk factors for CMPA, while exclusive breastfeeding (OR=0.21, 95%CI: 0.08-0.58, P<0.05) and the introduction of complementary food at an age of >6 months (OR=0.38, 95%CI: 0.17-0.86, P<0.05) were protective factors., Conclusions: The introduction of complementary food at an age of <4 months, maternal food allergy, and antibiotic exposure during pregnancy are risk factors for CMPA in infants.

Sepsis-associated acute kidney injury (AKI) is a life threatening condition with high morbidity and mortality. The pathogenesis of AKI is associated with apoptosis. In this study, we investigated the effects of ligustrazine (LGZ) on experimental sepsis-associated AKI in mice. Sepsis-associated AKI was induced in a mice model using cecal ligation and puncture (CLP) method. Mice were administered LGZ (10, 30, and 60 mg/kg) via tail vein injection 0.5 h before CLP surgery. Mice survival was evaluated. Renal water content was detected. Urine samples were collected for ELISA of Kim1. Kidneys were collected for nucleic acid analysis and histological examination. Pathological assessment was used to determine the effect of LGZ on sepsis-associated AKI. Caspase-3 expression in kidney was assessed by immunohistochemistry. Renal NMDAR1 level was also determined. Treatment of LGZ improved mice survival rate; the effect was significant when administered at a high LGZ dose (60 mg/kg). Renal water content of mice undergoing CLP was significantly reduced by LGZ treatment. Both middle-dose and high-dose LGZ treatments reduced urine Kim1 level in sepsis-associated AKI mice. The severity of AKI in septic mice was reduced by middle-dose and high-dose LGZ administration. Immunohistochemical analysis revealed decreased caspase-3 and NMDAR1 levels in the kidney following middle-dose and high-dose LGZ treatments. RT-PCR assay showed a significant reduction in NMDAR1 mRNA expression in the kidney of middle-dose and high-dose LGZ-treated mice. LGZ exhibited protective effects against sepsis-associated AKI in mice, possibly via downregulation of renal NMDAR1 expression and its anti-apoptotic action by inhibiting caspase-3.

This study focused on the microbiota and chemical compounds of the fermented Pinelliae Rhizoma produced in Longchang (LC), Zizhong (ZZ) and Xindu (XD), in Sichuan Province (China). High-throughput sequencing was used to analyze the microbiota. GC-MS and LC-MS were used to detect the compounds produced during the three different Pinelliae Rhizoma fermentation processes. The bacteria and fungi of the three fermented Pinelliae Rhizoma differed substantially, with the bacterial content mainly composed of the Bacillus genus, while the common fungi were only included in four OTUs, which belong to three species of Eurotiomycetes and Aspergillus cibarius . 51 volatile compounds were detected; they varied between LC, XD, and ZZ fermented Pinelliae Rhizoma . C10 and C15 terpenes were most frequently detected, and only curcumene and β-bisabolene were detected in the three fermented Pinelliae Rhizoma . 65 non-volatile compounds were detected by LC-MS, most were of C16, C18, C20, C21 and C22 structures. Cluster analysis showed more similarity between LC and XD fermented Pinelliae Rhizoma with regards to volatile compound content, but more similarity between the XD and ZZ fermented Pinelliae Rhizoma for non-volatiles. Moreover, no correlation between geographical distance and microflora or compounds of fermented Pinelliae Rhizoma was observed. These results showed that hundreds of compounds are produced by the natural mixed fermentation of Pinelliae Rhizoma , and may mostly relate to the microorganisms of five species., This study focused on the microbiota and chemical compounds of the fermented Pinelliae Rhizoma produced in Longchang (LC), Zizhong (ZZ) and Xindu (XD), in Sichuan Province (China). High-throughput sequencing was used to analyze the microbiota. GC-MS and LC-MS were used to detect the compounds produced during the three different Pinelliae Rhizoma fermentation processes. The bacteria and fungi of the three fermented Pinelliae Rhizoma differed substantially, with the bacterial content mainly composed of the Bacillus genus, while the common fungi were only included in four OTUs, which belong to three species of Eurotiomycetes and Aspergillus cibarius . 51 volatile compounds were detected; they varied between LC, XD, and ZZ fermented Pinelliae Rhizoma . C10 and C15 terpenes were most frequently detected, and only curcumene and β-bisabolene were detected in the three fermented Pinelliae Rhizoma . 65 non-volatile compounds were detected by LC-MS, most were of C16, C18, C20, C21 and C22 structures. Cluster analysis showed more similarity between LC and XD fermented Pinelliae Rhizoma with regards to volatile compound content, but more similarity between the XD and ZZ fermented Pinelliae Rhizoma for non-volatiles. Moreover, no correlation between geographical distance and microflora or compounds of fermented Pinelliae Rhizoma was observed. These results showed that hundreds of compounds are produced by the natural mixed fermentation of Pinelliae Rhizoma , and may mostly relate to the microorganisms of five species.

The purpose of this meta-analysis was to compare the ability of the qSOFA in predicting short- (≤30 days or in-hospital mortality) and long-term (>30 days) mortality among patients outside the intensive care unit setting. Studies reporting on the qSOFA and mortality were searched using MEDLINE and SCOPUS. Studies were included if they involved patients presenting to the ED with suspected infection and usage of qSOFA score for mortality prognostication. Data on qSOFA scores and mortality rates were extracted from 36 studies. The overall pooled sensitivity and specificity for the qSOFA were 48% and 86% for short-term mortality and 32% and 92% for long-term mortality, respectively. Studies reporting on short-term mortality were heterogeneous (Odd ratio, OR = 5.6; 95% CI = 4.6-6.8; Higgins's I 2  = 94%), while long-term mortality studies were homogenous (OR = 4.7; 95% CI = 3.5-6.1; Higgins's I 2  = 0%). There was no publication bias for short-term mortality analysis. The qSOFA score showed poor sensitivity but moderate specificity for both short and long-term mortality, with similar performance in predicting both short- and long- term mortality. Geographical region was shown to have nominal significant (p = 0.05) influence on qSOFA short-term mortality prediction.

The clinical treatment of gastric cancer is hampered by the development of anticancer drug resistance as well as the unfavorable pharmacokinetics, nontarget toxicity, and inadequate intratumoral accumulation of current chemotherapies. The polyphenol epigallocatechin gallate in combination with doxorubicin exhibits synergistic inhibition P-glycoprotein efflux pump activity and cancer cell growth. This study evaluated a potential activated nanoparticle delivery system comprising a hyaluronic acid complex with polyethylene glycol-conjugated gelatin containing encapsulated epigallocatechin gallate and low-dose doxorubicin, which may facilitate targeted drug administration to gastric cancer cells. We confirmed successful delivery of bioactive combination drugs and internalization into gastric cancer cells through CD44 ligand recognition and ensuing inhibition of cell proliferation via caspase-induced apoptosis and G2/M phase cell cycle arrest. Furthermore, the targeted nanoparticles significantly suppressed gastric tumor activity and reduced both tumor and heart tissue inflammatory reaction in vivo compared to systemic combination treatment.

Background: Patients undergoing upper gastrointestinal endoscopic surgeries are generally placed in the left lateral position and require endotracheal intubation to maintain airway patency. We conducted a prospective, randomized, controlled study to evaluate the feasibility of intubation under video laryngoscopic guidance in the left lateral position during upper gastrointestinal endoscopic surgery., Methods: We compared the data of patients (n = 120) who underwent intubation under video laryngoscopic guidance in the supine or left lateral position. Patients in Group S (n = 59) were initially placed in the supine position and then shifted to the left lateral position after airway establishment. Patients in Group L (n = 61) were placed in the left decubitus position during both induction and intubation. Laryngoscopic view, intubation time, success rate, hemodynamic changes, adverse effects, and complications of intubation were compared between the groups., Results: The 2 groups showed no difference in terms of time required for intubation (Group L, 23.95 ± 4.43 seconds and Group S, 23.44 ± 4.78 seconds; P = .545) and number of intubation attempts. Further, the overall rate of intubation success was 100% in both groups. However, Group S exhibited significant hemodynamic changes during shift of decubitus (P < .001) and severe sore throat (P = .030). The incidences of other adverse effects such as productive cough, dryness of mouth, hoarseness, oral mucosal injury, dental injury, and hypoxia in the 2 groups were comparable., Conclusion: We concluded that intubation in the lateral position under video laryngoscopic guidance is safe and feasible performed in the left lateral position and prevents the hemodynamic change and sore throat resulting from change in decubitus., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Study Objective: To determine the appropriate mean arterial pressure (MAP) control level for elderly patients with hypertension during the perioperative period., Design: A prospective, randomized study., Setting: Three teaching hospitals in China., Patients: Six hundred seventy-eight elderly patients with chronic hypertension undergoing major gastrointestinal surgery., Interventions: Patients were randomly allocated to three groups and the target MAP level was strictly controlled to one of three levels: level I (65-79mmHg), level II (80-95mmHg), or level III (96-110mmHg)., Measurements: The primary outcome was acute kidney injury (AKI) (50% or 0.3mg·dL -1 increase in creatinine level) during the first 7 postoperative days. The secondary outcomes were perioperative adverse complications. Moreover, vasoactive agents were observed during surgery., Main Results: The overall incidence of postoperative AKI was 10.9% (71/648). AKI occurred significantly less often in patients with level II MAP control (6.3%;13/206) than in patients with level I (13.5%; 31/230) and level III (12.9%; 27/210) (P<0.001) MAP control. Level II was associated with lower incidences of hospital-acquired pneumonia (6.7%; 14/206; P=0.014) and admission to the intensive care unit (ICU) (4.4%; 9/206; P=0.015) and with shorter length of stay in the ICU (P=0.025) when compared with level I and level III. Use of norepinephrine, phenylephrine, and nitroglycerin was significantly higher for patients with level III MAP control than for patients with level I and level II MAP control (P=0.001)., Conclusions: For elderly hypertensive patients, controlling intraoperative MAP levels to 80 to 95mmHg can reduce postoperative AKI after major abdominal surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder. Previous research has indicated that genetic factors, family education, environment and dietary habits are associated with ADHD. It has been determined that in China many children with ADHD also have allergic rhinitis or asthma. These children are more susceptible to the common cold or upper respiratory infections compared with normal healthy children. Additionally, the common cold or an upper respiratory infection may lead to disease recurrence or worsen the symptoms in these children. Previous studies have determined that ADHD may have a close association with allergic disease. Based on the clinically observed phenomenon and previous studies, it was hypothesized that ADHD is a high inflammation and immune‑associated disease. Therefore, the authors designed clinical and animal experiments to test this hypothesis in the future. Immune system disorders may be a novel part of the etiology of ADHD. The current report may have implications for future clinical practice.

Background: A newly defined Cordyceps species, Ophiocordyceps formosana (O. formosana) has been implicated in multitudinous bioactivities, including lowering glucose and cholesterol levels and modulating the immune system. However, few literatures demonstrate sufficient evidence to support these proposed functions. Although the use of Cordyceps spp. has been previously addressed to improve insulin insensitivity and improve the detrimental symptoms of depression; its mechanistic nature remains unsettled. Herein, we reveal the effects of O. formosana in ameliorating hyperglycemia accompanied with depression., Methods: Diabetes was induced in mice by employing streptozotocin(STZ), a chemical that is toxic to insulin-producing β cells of the pancreas. These streptozotocin (STZ)-induced diabetic mice showed combined symptoms of hyperglycemia and depressive behaviors. Twenty-four STZ-induced mice were randomly divided into 3 groups subjected to oral gavage with 100 μL solution of either PBS or 25 mg/mL Ophiocordyceps formosana extract (OFE) or 2 mg/mL rosiglitazone (Rosi, positive control group). Treatments were administered once per day for 28 days. An additional 6 mice without STZ induction were treated with PBS to serve as the control group. Insulin sensitivity was measured by a glucose tolerance test and levels of adiponectin in plasma and adipose tissue were also quantified. Behavioral tests were conducted and levels of monoamines in various brain regions relating to depression were evaluated., Results: HPLC analysis uncovered three major constituents, adenosine, D-mannitol and cordycepin, within O. formosana similar to other prestigious medicinal Cordyceps spp.. STZ-induced diabetic mice demonstrated decreased body weight and subcutaneous adipose tissue, while these symptoms were recovered in mice receiving OFE treatment. Moreover, the OFE group displayed improved insulin sensitivity and elevated adiponectin within the plasma and adipose tissue. The anti-depressive effect of OFE was observed in various depression-related behavior tests. Concurrently, neurotransmitters, like 5-HT and dopamine in the frontal cortex, striatum and hippocampus were found to be up-regulated in OFE-treated mice., Conclusions: Our findings illustrated, for the first time, the medicinal merits of O. formosana on Type I diabetes and hyperglycemia-induced depression. OFE were found to promote the expression of adiponectin, which is an adipokine involved in insulin sensitivity and hold anti-depressive effects. In addition, OFE administration also displayed altered levels of neurotransmitters in certain brain regions that may have contributed to its anti-depressive effect. Collectively, this current study provided insights to the potential therapeutic effects of O. formosana extracts in regards to hyperglycemia and its depressive complications.

The substantial merit of Cordyceps s.l. spp. in terms of medicinal benefits is largely appreciated. Nevertheless, only few studies have characterized and examined the clinical complications of the use of health tonics containing these species. Here, we epitypified C. formosana isolates that were collected and characterized as Ophiocordyceps formosana based on morphological characteristics, molecular phylogenetic analyses, and metabolite profiling. Thus, we renamed and transferred C. formosana to the new protologue Ophiocordyceps formosana (Kobayasi & Shimizu) Wang, Tsai, Tzean & Shen comb. nov. Additionally, the pharmacological potential of O. formosana was evaluated based on the hot-water extract from its mycelium. The relative amounts of the known bioactive ingredients that are unique to Cordyceps s.l. species in O. formosana were found to be similar to the amounts in O. sinensis and C. militaris, indicating the potential applicability of O. formosana for pharmacological uses. Additionally, we found that O. formosana exhibited antioxidation activities in vitro and in vivo that were similar to those of O. sinensis and C. militaris. Furthermore, O. formosana also displayed conspicuously effective antitumor activity compared with the tested Cordyceps s.l. species. Intrinsically, O. formosana exhibited less toxicity than the other Cordyceps species. Together, our data suggest that the metabolites of O. formosana may play active roles in complementary medicine.

Objective: To investigate the variations of macular thickness and peripapillary retinal nerve fiber layer (RNFL) thickness in myopic children., Methods: A total of 96 eyes from 48 myopic children at department of Ophthalmology, Second Affiliated Hospital of Wenzhou Medical College from September 2010 to March 2012 were enrolled in this study and divided into three groups (low, moderate and high myopia group) according to the severity of myopia. Another 33 eyes from 19 emmetropic children were recruited as control group. The macular thickness and peripapillary RNFL thickness of the myopic children measured by optical coherence tomography were compared with that of the control group., Results: The mean thickness of nasal, superior and inferior regions of outer-ring macular in the high myopia group were 276 µm, 294 µm, 285 µm respectively, which were significantly lower than that in the control group (P < 0.05). The mean thickness of superior of outer-ring macular in the low and moderate groups were 302 µm, 301 µm respectively, and the inferior of outer-ring ones were 288 µm, 283 µm respectively, which were significantly lower than that in the control group (P < 0.05). The temporal region of peripapillary RNFL thickness was significantly greater, and the other six regions of RNFL thicknesses were significantly lower in the high group than in the control group (P < 0.05). The central-1 mm, superior region of inner-ring, temporal and superior region of outer-ring macular thickness had positive correlations with spherical equivalent (SE) (P < 0.05). There was a negative correlation between the temporal peripapillary RNFL thickness and SE, while positive correlations were found between other regions of peripapillary RNFL thickness and SE (P < 0.05)., Conclusions: The thicknesses of macular and peripapillary RNFL of myopic children have already redistributed before apparent changes of funds.

With an intention to synergize the anti-bacterial activity of 5-aryloxy pyrazole and rhodanine derivatives, eight series of hybrid compounds have been synthesized and evaluated for their antibacterial activity. The majority of the synthesized compounds showed good inhibitory activity against selected methicillin resistant and quinolone-resistant Staphylococcus aureus (MRSA, QRSA) with minimum inhibitory concentration (MIC) values in the range of 1-32 μg/mL. The cytotoxicity test suggests that these compounds exhibited in vitro antibacterial activity at non-cytotoxic concentrations. These studies therefore suggest that rhodanine-based 5-aryloxy pyrazoles are interesting scaffolds for the development of novel Gram-positive antibacterial agents., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

In the purpose of increasing incorporation efficiency and improving the release kinetics of plasmid DNA (pDNA) from poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles, a facile method for the fabrication of calcium phosphate (CaPi) embedded PLGA nanoparticles (CaPi-pDNA-PLGA-NPs) was developed. The effect of several preparation factors on the particle size, incorporation efficiency, pDNA release and transfection efficiency in vitro was studied by Single Factor Screening Method. These preparation factors included the molecular weight (MW), hydrolysis degree (HD) of polyvinyl alcohol (PVA), sonication power and time, composition of organic phase, initial concentration of calcium phosphate and calcium (Ca) to phosphate ion (P) ratio (Ca/P ratio), etc. The CaPi-pDNA-PLGA-NPs made according to the optimal formulation were spherical in shape observed by transmission electron microscopy (TEM) with a mean particle size of 207±5 nm and an entrapment efficiency of 95.7±0.8%. Differential scanning calorimetry (DSC) suggested that there existed interaction between the DNA-calcium-phosphate (CaPi-pDNA) complexes and the polymeric matrices of PLGA. X-ray diffractometry (XRD) further proved the conclusion and indicated that the CaPi-pDNA was in weak crystallization form inside the nanoparticles. The Brunauer-Emmett-Teller (BET) surface area measurement demonstrated that the CaPi-pDNA-PLGA-NPs are mesoporous with specific surface area of 57.5m(2)/g and an average pore size of 96.5 Å. The transfection efficiency of the CaPi-pDNA-PLGA-NPs on human embryonic kidney 293 (HEK 293) cells in vitro was 22.4±1.2%, which was much higher than those of both the pDNA loaded PLGA nanoparticles (pDNA-PLGA-NPs) and the CaPi-pDNA embedded PLGA microparticles (CaPi-pDNA-PLGA-MPs). The CaPi-pDNA-PLGA-NPs are promising vectors for gene delivery., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Methylglyoxal (MG) is a metabolite of glucose. The serum MG level is increased in diabetic patients, and MG is implicated in diabetic complications related to embryonic development injury. We previously reported cytotoxic effects of MG on mouse embryonic stem cells and blastocysts, and a further association with defects in subsequent development. Here, we further investigate the effects of MG on oocyte maturation and subsequent pre- and post-implantation development, both in vitro and in vivo. Notably, MG induced a significant reduction in the rate of oocyte maturation, fertilization, and in vitro embryonic development. Treatment of oocytes with MG during in vitro maturation (IVM) led to increased resorption of post-implantation embryos and decreased fetal weight. Experiments with an in vivo mouse model disclosed that consumption of drinking water containing 10-20 microM MG led to decreased oocyte maturation and in vitro fertilization, as well as early embryonic developmental injury. Finally, pretreatment with a caspase-3-specific inhibitor effectively prevented MG-triggered injury effects, suggesting that embryo impairment by MG occurs via a caspase-dependent apoptotic process., (2010 Elsevier Ireland Ltd. All rights reserved.)

The study is aimed to establish a RP-HPLC method for determination of luteolin from the extracts of Elsholtzia blanda (EEB) in rats' biological specimen. A RP-HPLC method was established for determination of free and total luteolin in SD rats' plasma and gastrointestinal tract and total luteolin in SD rats' heart, liver, lung and kidney at 0.17, 0.5, 1, 2, 4 and 6 h after administration of EEB to 24 male SD rats (4 rats per one time spot). Luteolin glycoside was hydrolyzed to aglycone luteolin in intestinal tract, and then luteolin was absorbed. The main form of luteolin existed in gastrointestinal tract after administration of EEB is aglycone. The content of luteolin in liver and kidney were higher than that in heart and lung. The content of luteolin in kidney, heart and lung were showed max at 1 h. Its peak time was similar to that in blood. However, in liver, the drug was distributed quickly, and showed max at 0.17 h. And because of the sensitivity of the method, luteolin was not be detected in other tissues. The method is sensitive, specific, accurate, and is appropriate for determination of luteolin in vivo.

A thermally stable and alkalophilic xylanase, XynCDBFV, from Neocallimastix patriciarum was overexpressed in Escherichia coli as a recombinant protein fused to the N-terminus of oleosin, a unique structural protein of seed oil bodies. As a result of the reconstitution of the artificial oil bodies (AOBs), the immobilization of active xylanase was accomplished. Response surface methodology (RSM) was employed for the optimization of the immobilized xylanase activity. The central composite design (CCD) and regression analysis methods were effective for determination of optimized temperature and pH conditions for the AOB-immobilized XynCDBFV. The optimal condition for the highest immobilized xylanase activity (3.93IU/mg of total protein) was observed at 59 degrees C and pH 6.0. Further, AOB-immobilized XynCDBFV retained 50% of its maximal activity after 120min at 60 degrees C, and it could be easily and simply recovered from the surface of the solution by brief centrifugation, and could be reused eight times while retaining more than 60% of its activity. These results proved it is a simple and effective method for direct immobilization of xylanases.

Multiple myeloma (MM) is a clonal plasma cell malignancy, which is currently incurable. Therefore, new mono- or combined therapy treatment regimens in the early and advanced phases of MM are urgently needed to combat this disease. Recently, p38 mitogen-activated protein kinase (MAPK) has been implicated as playing an important role in MM. Therefore, the effect of a p38alpha-selective MAPK inhibitor, SCIO-469 (indole-5-carboxamide, ATP-competitive inhibitor), or its structural analog, SD-282 (indole-5-carboxamide, ATP-competitive inhibitor) was examined in mouse xenograft models of MM using human RPMI-8226 or H-929 plasmacytoma inocula. Oral treatment with SCIO-469 (10, 30, 90 mg/kg) twice daily was initiated in mice with palpable tumors of RPMI-8226 origin, a condition that mimics early human myeloma disease. In mice with palpable tumors, 14 days of SCIO-469 treatment significantly reduced RPMI-8226 tumor growth in a dose-dependent manner. A significant dose-dependent reduction in RPMI-8226 tumor growth was also observed when SCIO-469 oral treatment at doses of 10, 30 and 90 mg/kg twice daily was initiated in mice with tumors of pronounced size, a condition that mimics advanced human myeloma disease. In a similar set of studies employing the SCIO-469 analogue SD-282 at 90 mg/kg/bid orally, histological assessment at the end of the study demonstrated a significant reduction in RPMI-8226 tumor growth and angiogenesis. SD-282 treatment was additionally shown to significantly reduced expression of heat-shock protein-27 (HSP-27) and phospho-p38 in the tumor cells. Furthermore, co-administration of SCIO-469 with dexamethasone elicited antitumor properties in dexamethasone-sensitive H-929 tumors at much lower than the typically effective doses of dexamethasone, suggesting its potential for combined therapy. In conclusion, p38 inhibitors reduced human myeloma cell growth in vivo both at early and advanced phases of the disease. The current study also provides evidence of potential for co-therapy with dexamethasone.

An RP-HPLC method for determination of luteolin from Elsholtzia blanda Benth. extracts in rats' plasma was established and the pharmacokinetics of luteolin in rats was studied. Drug blood samples from caudal vein were gotten after oral administration of luteolin. Plasma samples were determined by RP-HPLC after being deproteinized with trichloroacetic acid and extracted with ethyl acetate. The calibration curve was linear in the range of 0.37-47.27 microg x mL(-1). The limit of quantification was 0.37 microg x mL(-1). The method recovery of luteolin was 93%-99%. The extract recovery was 75%-85%. RSDs of intra-and inter-day precisions were less than 5%. The concentration-time curve of luteolin after oral administration of Elsholtzia blanda Benth. extracts was fitted to two compartment open model. Two factors analysis of variance were adopted in the evaluation of gender and time spots for collection of blood. The result suggested that the gender-based difference in blood-drug concentrations had statistical significance. The metabolite in blood was identified as galcuronide. The method is sensitive, specific, accurate, and is appropriate for determination of luteolin in vivo.

The paper summarizes the interactions between luteolin (glucosides) and drug-metabolizing enzyme from the literature of recent years and our research work. The metabolism of luteolin is chiefly mediated by phase II metabolic enzyme. Its glucosides are firstly hydrolyzed into aglycone in intestinal tract, and then absorbed and metabolized. Luteolin has the effect on the induction of CYP3A, and on the inhibition of CYPIA, 1B and 2E. Also, luteolin is an effective inhibitor of CYP2B6, CYP2C9 and CYP2D6. Luteolin can induce and inhibit UGTs and SULTs. It can also inhibit multi ABC transport proteins. Understanding the interactions between luteolin (glucosides) and drug-metabolizing enzyme has an important significance in guiding clinical use of the drug.

Objective: To observe the excretion of luteolin after oral administration of Elsholtzia blanda benth extracts in rats., Methods: Samples of urine, feces and bile were collected after oral administration of Elsholtzia blanda benth extracts in rate. After deconjugation with beta-glucuronidase/sulfatase, the levels of luteolin in urine, feces and bile were measured by RP-HPLC., Result: The recovery rate of luteolin was 98.0 %-106.0 % and the extract recoveries were 85.0 %-108.0%. Relative standard deviation (RSD) of intra-and inter-day assay was less than 10.0 %. The total accumulative excretion was 37 % (11 % in urine, 26 % in feces and bile)., Conclusion: The established RP-HPLC method is sensitive, specific, accurate, and is applicable for determination of luteolin in rat urine,feces and bile.

Cell lines of Bcap37 and Bcap37/MDR1 (the high P-glycoprotein (P-gp) expressing cell line) were used as model to investigate the different accumulations of (E)-2-(4-(diethylamino methyl) benzylidene)-5,6-dimethoxy-2,3-dihydroinden-one (BYZX) in the two kinds of cells. It was authenticated that whether BYZX was the substrate of P-gp. Meanwhile, the inhibitive effects of BYZX on the P-gp were investigated by determining the fluorescence intensity of rhodamine 123 in the model cells, with and without BYZX. A reversed-phase high-performance liquid chromatography (RP-HPLC) method was used to determine the accumulations of BYZX in the two cells. The results showed that the amount of BYZX accumulation in Bcap37/MDR1 cells were as many as those in Bcap37 cells (P > 0.05), and the concentrations of BYZX accumulated in the Bcap37/MDR1 cells did not increase when co-incubated with P-gp inhibitor verapamil. Furthermore, different concentrations of BYZX also had no effects on the efflux of rhodamine 123 (P > 0.05). These results indicated that there were no interactions between BYZX and P-gp. BYZX will not be pumped out of the cells, and it also not inhibited the P-gp. It was the useful advantage for its absorption.

In vitro phase I metabolism of BYZX, a novel central-acting cholinesterase inhibitor for the treatment of the symptoms of Alzheimer's disease, was studied in human liver microsomes (HLM) and the metabolite formation pathways were investigated by chemical inhibition experiments and correlation analysis. The residual concentration of substrate and the metabolite formed in incubate were determined by HPLC method. The calibration curves of BYZX were linear over the concentration range from 5.07 microM to 200.74 microM. The relative standard deviations of within day and between day were less than 5% (n=5). The limit of detection (LOD) was 0.18 microg/mL (S/N=3) and the limit of quantification (LOQ) was 0.55 microg/mL (R.S.D.=5.2%, n=5). The determination recoveries of BYZX were in the range of 98.2-104.8%. The apparent K(m) of BYZX in HLM was 53.25+/-17.2 microM, the V(max) was 0.94+/-0.77 microM/min/mg protein, and the intrinsic clearance value (Cl(int)) was 0.018+/-0.02 mL/min/mg protein. Ketoconazole and cyclosporin A were the most potent inhibitors on BYZX metabolism in HLM with IC(50) being 0.89 microM and 18.17 microM, respectively. And the inhibition constant (K(i)) of ketoconazole was 0.42 microM. The metabolite of BYZX was N-des-ethyl-BYZX elucidated by LC-MS-MS. The results demonstrated that the developed HPLC method was reliability, simple technique, and was applicable to be used for the researches of in vitro metabolism of BYZX. CYP3A4 was the major isozyme responsible for BYZX metabolism; N-dealkylation was the major metabolic pathway of BYZX. The predominant metabolite of BYZX was N-des-ethyl-BYZX detected in vitro phase I metabolism in HLM.

With the aim of exploring the usefulness of spatial analysis in the formulation of a strategy for schistosomiasis japonica control in different environmental settings, a population-based database was established in Dangtu county, China. This database, containing the human prevalence of schistosomiasis at the village level from 2001 to 2004, was analyzed by directional trend analysis supported with ArcGIS 9.0 to select the optimum predictive approach. Based on the approach selected, different strata of prevalence were classified and the spatial distribution of human infection with Schistosoma japonicum was estimated. The second-order ordinary kriging approach of spatial analysis was found to be optimal for prediction of human prevalence of S. japonicum infection. The mean prediction error was close to 0 and the root-mean-square standardised error was close to 1. Starting with the different environmental settings for each stratum of transmission, four areas were classified according to human prevalence, and different strategies to control transmission of schistosomiasis were put forward. We conclude that the approach to use spatial analysis as a tool to predict the spatial distribution of human prevalence of S. japonicum infection improves the formulation of strategies for schistosomiasis control in different environmental settings at the county level.

Rutin deca(H-) sulfate sodium (RDS) is one of the most important drug candidates, which possesses very good activity as inhibitor of the complement system of warm-blooded animals and human immunodeficiency virus (HIV). In order to understand RDS metabolism and disposition, an ion-pairing coupled with solid-phase extraction technique (IP-SPE) was developed to extract RDS from rat plasma sample. Tetrabutyl ammonium bromide (TBAB) buffer (0.2 M, pH 8.0) was used as the ion-pairing extraction reagent and LC-18 was used as SPE sorbent. In addition, an ion-pairing HPLC method was established for the specific determination of RDS. A reversed phase C8 column was used for the separation of RDS and nitrendipine (internal standard). The mobile phase was composed of 10 mM phosphate buffer solution containing 25 mM TBAB-acetonitrile (52:48, v/v, pH 7.5). The calibration curve was linear from 0.3 to 30 nmol/mL. The analytical recovery from rat plasma was found to be 97.9+/-4.1% (n = 15). LOD and LOQ for RDS in plasma were calculated to be 0.12 nmol/mL and 0.30+/-0.024 nmol/mL (R.S.D. = 8.2%, n = 5), respectively. The intra- and inter-day precision was less than 9.2%. The assay was applied to a preliminary pharmacokinetic study in three male rats after those received a single intravenous bolus via caudal vein of 12 micromol/kg RDS.

Previous studies have established that ethanol induces cell apoptosis and necrosis. However, the precise molecular mechanisms are currently unclear. Here, we show that higher concentrations of ethanol (250-400 mM) induced a shift from apoptotic to necrotic cell death in human K562 cells, and that resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties, inhibited or enhanced ethanol-induced apoptosis/necrosis depending on the treatment dosage. Using the cell permeable dye 2',7'-dichlorofluorescin diacetate (DCF-DA) as an indicator of reactive oxygen species (ROS) generation, we showed that ethanol treatment directly increased intracellular oxidative stress. This intracellular oxidative stress increased in response to high concentrations (100-200 microM) of resveratrol, but remained unchanged following treatment with low concentrations (10-25 microM) of resveratrol. Further studies showed that resveratrol could attenuate or enhance ethanol-induced intracellular oxidative stress generation-dependent on treatment dosage, and that this effect could be correlated with cell apoptosis or necrosis. Importantly, ethanol-induced changes in intracellular ATP levels were also correlated with resveratrol dosage. Taken together, these results indicate that the treatment dosage may determine the effect of resveratrol on ethanol-induced ROS generation, intracellular ATP levels, and cell apoptosis or necrosis. Thus our findings support the possibility that appropriate dosage of resveratrol aids in decreasing the toxic effect of ethanol.

Background: In this study, we investigated the developmental functions and autistic profiles in children with Fragile X syndrome (FXS). In addition, we established the relationships between developmental and autistic profiles in these children., Methods: The medical records of 12 children with FXS, aged 2 to 7 years, were collected. Fifteen children with autism, without FXS, who were age- and sex-matched were selected as the comparison group. All children underwent assessments of developmental functions according to the Chinese Child Development Inventory (CCDI), and autistic profiles according to the Childhood Autism Rating Scale (CARS). Differences in genders between the two groups were determined with the Fisher's exact test. Differences in developmental functions (CCDI) and autistic profiles (CARS) between the two groups were compared using Mann-Whitney U test and Bonferroni adjustment. The Spearman's rho correlation was used to determine the relationship of developmental functions and autistic profiles., Results: All developmental functions in children with FXS were better than those with autism except for gross motor, fine motor and expressive language functions. Children with FXS had the worst expressive language function (56% Development Quotient, DQ) as compared with other developmental functions (> 70% DQ). The major difference between the children with FXS and those with autism was personal social function with a difference of 33% DQ. The average total CARS score were lower in children with FXS (average score, 28) than children with autism (average score, 34). Spearman's correlation demonstrated the CARS total score were negatively correlated with all developmental functions, except for gross motor function., Conclusions: Our findings suggest that the FXS children had multifaceted and disproportional development patterns in motor, speech and social domains when compared with the autism children without FXS. The developmental functions were inversely correlated with autistic profiles. Therefore, when applying comprehensive assessment, we were able to identify the special developmental features in children with FXS.