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Platelet aggregates, such as PRP, PRF, and CGF, have been used alone or in combination with other grafting materials to enhance restoration outcomes. The process for preparing these autografting materials requires two-step centrifugation or specific centrifuges. In this study, we obtained an injectable fibrin scaffold (IFS) rich in growth factors by one-step centrifugation of whole blood from rabbits. The purpose of this study is to introduce some characteristics of IFS. This scaffold was characterized using various techniques, including Masson’s trichrome staining, scanning electron microscopy, porosity measurements, and cell counting. The sustained release of growth factors, including PDGF, VEGF, TGF-β1, IGF, FGF, and EGF, was quantified using ELISA assay. The obtained IFS was tested for its effects on cell proliferation, extracellular matrix deposition, and full-thickness skin defect repair. The prepared IFS is characterized by a loose fibrin network structure with white blood cells and platelets that slowly release growth factors and can promote the healing of skin defects via the promotion of cell proliferation, collagen deposition, and tissue revascularization. In addition, its liquid properties and porous structure are conducive to its application as a therapeutic component in tissue engineering.

This research explored the HPLC fingerprints of Hypericum attenuatum Choisy, which has anti-arrhythmic activity. HPLC was adopted to perform a determination of chemical fingerprints of H. attenuatum specimens acquired through seven distinct sources. The anti-arrhythmic activity of each H. attenuatum sample was obtained through pharmacodynamics experiments in animals. A regression analysis and correlation analysis were utilized to calculate the relationship of the peak and pharmacological effectiveness with the identified peak. Peaks numbered 5, 7, 13 and 14 in the fingerprint were regarded as the likely anti-arrhythmic agents. The fingerprint was compared with reference standards for identification of the correlative peaks. Liquid chromatography–time-of-flight–mass spectrometry was applied to identify its structure. As a consequence, a universal model was established for the utilization of HPLC to investigate anti-arrhythmic activity and the spectrum-effect relationship among H. attenuatum. This model is available for the discovery of the major bioactive constituents of Hypericum.

Typhoid fever is a life-threatening disease caused by Salmonella enterica serovar Typhi (S. Typhi) and remains a significant public health burden in developing countries. In China, typhoid fever is endemic with a limited number of reported outbreaks. Recently, Chinese local Center for Disease Prevention and Control is starting to apply whole genome sequencing for tracking the source of outbreak isolates. In this study, we conducted a retrospective investigation into a community outbreak of typhoid fever in Lanling, China, in 2016. A total of 26 S. Typhi isolates were recovered from the drinking water (n = 1) and patients' blood (n = 24) and stool (n = 1). Phylogenetic analysis indicated the persistence of the outbreak isolates in drinking water for more than 3 months. The genomic comparison demonstrated a high similarity between the isolate from water and isolates from patients in their genomic content, virulence gene profiles, and antimicrobial resistance gene profile, indicating the S. Typhi isolate from drinking water was responsible for the examined outbreak. The result of pulsed-field gel electrophoresis (PFGE) revealed these isolates had identical PFGE pattern, indicating they are clonal variants. Additionally, phylogeographical analysis of global S. Typhi isolates suggested the outbreak isolates are evolutionarily linked to the isolates from the United Kingdom and Vietnam. Taken together, this study highlights the drinking water and international travel as critical control points of mitigating the outbreak, emphasizing the necessity of regular monitoring of this pathogen in China.

The search for active, stable, and cost-effective electrocatalysts for hydrogen evolution reaction (HER) is desirable, but it remains a great challenge in the overall water splitting. Here, we report the synthesis of nickel boron nanoparticles supported on Vulcan carbon (Ni-B) via a simple, yet scalable, two-step chemical reduction–annealing strategy. The results of the electrochemical measurements suggest that the overpotentials of Ni-B-400 are 114 and 215 mV (in 1 mol L−1 KOH) at current densities of 10 and 40 mA cm−2, respectively, indicating an exceedingly good electrocatalytic activity in the HER. More importantly, Ni-B maintains a current density of 7.6 mA cm−2 at an overpotential of 0.15 V for 20 h in the durability test. The excellent HER activity of Ni-B-400 is derived from the small particle size and the expanded lattice of Ni, which can optimize the hydrogen absorption energy and enhance the electrocatalytic properties.

Objective: Most patients with spinal cerebrospinal fluid (CSF) leakage require an epidural blood patch (EBP); however, the response to treatment is varied. This study aimed to compare the MRI findings at follow-up between EBP effective and non-effective groups and to identify imaging findings that predict EBP treatment failure. Methods: We retrospectively reviewed 48 patients who received EBP treatment for spinal CSF leakage. These patients were stratified into two groups: EBP effective (n = 27) and EBP non-effective (n = 21) using the results of the 3 month MRI as the end point. Results: Compared to the EBP non-effective group, the patients in the EBP effective group had a lower spinal CSF leakage number (2.67 vs 12.48; p = 0.001), lower spinal epidural fluid accumulation levels (3.00 vs 7.48; p = 0.004), brain descend (11.11% vs 38.10%; p = 0.027), pituitary hyperemia (18.52% vs 57.14%; p = 0.007), and decreased likelihood of ≥three numbers of spinal CSF leakage (25.93% vs 90.48%; p = 0.001) in the post-EBP MRI. Clinical non-responsiveness (OR: 57.84; 95% CI: 3.47–972.54; p = 0.005) and ≥three numbers of spinal CSF leakage (OR: 15.13; 95% CI: 1.45–159.06; p = 0.023) were associated with EBP failure. Between these variables, ≥three numbers of spinal CSF leakage identified using the post-EBP MRI demonstrated greater sensitivity in predicting EBP failure compared to clinical non-responsiveness (90.48% vs 61.9%). Conclusion: The number of spinal CSF leakage identified using the post-EBP MRI with a cut-off value of three is an effective predictor of EBP failure. Advances in knowledge: Compared to clinical responsiveness, the post-EBP MRI provided a more objective approach to predict the effectiveness of EBP treatment in patients with spinal CSF leakage.

Thromboembolism is a critical event in patients with coronavirus disease (COVID)-19 infection and highly associated with neutrophil extracellular traps. D-dimer has been found to be an essential thromboembolism-associated biomarker, however, the association between absolute neutrophil count (ANC) and level of D-dimer in patients with COVID-19 infection remains unclear. In this study, we enrolled consecutive patients with COVID-19 admitted to Taichung Veterans General Hospital (TCVGH), a referral center in central Taiwan with 20 airborne infection isolation rooms. Spearman correlation was used to determine the association between ANC and level of D-dimer in distinct time periods. A total of 28 consecutive patients with COVID-19 infection were enrolled, and 32.1% (9/28) of them required mechanical ventilation. Patients requiring mechanical ventilation had a higher ANC (8225 vs. 3427/µL, p &lt, 0.01) and levels of D-dimer (6.0 vs. 0.6 mg/L, p &lt, 0.01) compared with those without mechanical ventilation. Notably, we identified five patients with image-proven thromboembolic events during the hospital course, with the number of patients with pulmonary embolism, venous thrombosis and acute ischemic stroke were 2, 1, and 2, respectively. We found that ANC within 4 days correlated with the level of D-dimer to a moderate level (r = 0.71, p &lt, 0.05), and the association between ANC and D-dimer no longer exist after day 5. In conclusion, we found highly prevalent thromboembolic events among patients with severe COVID-19 infection in central Taiwan and identified the association between early ANC and D-dimer. More studies are warranted to elucidate the underlying mechanism.

Wen-Sheng Tzeng,1,2 Wei-Lin Teng,3 Pao-Hsien Huang,4 Tzu-Ching Lin,3 Feng-Lin Yen,2,5– 7 Yow-Ling Shiue2 1Department of Radiology, Pingtung Christian Hospital, Pingtung, Taiwan; 2Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan; 3Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 4School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanCorrespondence: Feng-Lin YenDepartment of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, No.100, Shin-Chuan 1st Road, Sanmin Dist., Kaohsiung City, 80708, TaiwanTel +886 7 3121101 ext 2028Email flyen@cc.kmu.edu.twYow-Ling ShiueInstitute of Biomedical Sciences, National Sun Yat-Sen University, No 70 Lien-Hai Road., Kaohsiung City, 80424, TaiwanTel +886 7 5252000 ext 5818Email shirley@imst.nsysu.edu.twPurpose: Transcatheter arterial chemoembolization (TACE) is a common clinical treatment for hepatocellular carcinoma (HCC). However, hypoxia induction after treatment might trigger tumor invasiveness and metastasis. Although pterostilbene (PTS) has antitumor effects, its chemoprevention in HepG2 cells under hypoxia has not been investigated yet. In addition, the poor water solubility of raw PTS limits its clinical application. Here, we prepared nanoparticles of PTS (PSN) and compared their antihepatoma activities with those of raw PTS in HepG2 under hypoxic conditions.Materials and Methods: The PTS nanoparticle formulation was prepared by nanoprecipitation, using Eudragit® e100 (EE) and polyvinyl alcohol (PVA) as carriers. We analyzed the physicochemical properties of raw PTS and PSN, including yield, encapsulation efficiency, water-solubility, particle size, morphology, crystalline-to-amorphous transformation, and molecular interaction between PTS and carriers. We also evaluated their antihepatoma activities under hypoxia treatment in HepG2 cells, including cell viability, hypoxia, and apoptosis.Results: The yield and encapsulation efficiency of PSN were 86.33% and > 99%, respectively. The water solubility and drug release of PTS were effectively improved after nanoprecipitation corresponding to the reduction in particle size, amorphous transformation, and formation of hydrogen bonding with carriers. PSN had a better cytotoxic effect than raw PTS in HepG2 under pre- and post-hypoxia conditions. In addition, hypoxia- and apoptosis-related proteins in HepG2 cells under two different hypoxic conditions were significantly inhibited by PSN compared with the control group with hypoxia only, except for HIF-1α in the post-hypoxia group. PSN was also significantly better in inhibiting these proteins, except for Bcl2, under pre-hypoxic conditions.Conclusion: Our results suggested that PSN could improve the water solubility and drug release of PTS and enhance the efficacy of HCC treatment under hypoxic conditions.Keywords: hepatocellular carcinoma, hypoxia, transcatheter arterial chemoembolization

Obesity that is highly associated with numerous metabolic diseases has become a global health issue nowdays. Plant sesterterpenoids are an important group of natural products with great potential; thus, their bioactivities deserve extensive exploration. RNA-seq analysis indicated that leucosceptroid B, a sesterterpenoid previously discovered from the glandular trichomes of Leucosceptrum canum, significantly regulated the expression of 10 genes involved in lipid metabolism in Caenorhabditis elegans. Furthermore, leucosceptroid B was found to reduce fat storage, and downregulate the expression of two stearoyl-CoA desaturase (SCD) genes fat-6 and fat-7, and a fatty acid elongase gene elo-2 in wild-type C. elegans. In addition, leucosceptroid B significantly decreased fat accumulation in both fat-6 and fat-7 mutant worms but did not affect the fat storage of fat-6; fat-7 double mutant. These findings indicated that leucosceptroid B reduced fat storage depending on the downregulated expression of fat-6, fat-7 and elo-2 and thereby inhibiting the biosynthesis of the corresponding unsaturated fatty acid. These findings provide new insights into the development and utilization of plant sesterterpenoids as potential antilipemic agents.

In this study, we investigated the roles of RIP1/RIP3 mediated cardiomyocyte necroptosis in CVB3-induced acute myocarditis. Serum concentrations of creatinine kinase (CK), CK-MB, and cardiac troponin I were detected using a Hitachi Automatic Biochemical Analyzer in a mouse model of acute VMC. Histological changes in cardiac tissue were observed by light microscope and expression levels of RIP1/RIP3 in the cardiac tissue were detected via Western blot and immunohistochemistry. The data showed that RIP1/RIP3 was highly expressed in cardiomyocytes in the acute VMC mouse model and that the necroptosis pathway specific blocker, Nec-1, dramatically reduced the myocardial damage by downregulating the expression of RIP1/RIP3. These findings provide evidence that necroptosis plays a significant role in cardiomyocyte death and it is a major pathway for cell death in acute VMC. Blocking the necroptosis pathway may serve as a new therapeutic option for the treatment of acute viral myocarditis.

Pituitary tumors are generally intracranial neoplasms with high incidence and mortality rates. The investigation of novel factors involved in the tumorigenesis of pituitary tumors and the characterization of the underlying molecular mechanisms is urgently required for the diagnosis and treatment of pituitary tumors. Accumulating evidence has indicated that microRNAs (miRs) serve important roles in the initiation and progression of cancer. The present study found that miR‑1 was significantly downregulated in pituitary tumor tissues upon reverse transcription‑quantitative polymerase chain reaction analysis. Decreased expression of miR‑1 was associated with the progression and worse prognosis of patients with pituitary tumors. The MTT assay showed that overexpression of miR‑1 significantly suppressed proliferation. Highly expressed miR‑1 promoted the apoptosis of pituitary tumor cells upon fluorescence‑activated cell sorting analysis. Further molecular study revealed that glucose‑6‑phosphate dehydrogenase (G6PD), the first and rate‑limiting enzyme of the pentose phosphate pathway (PPP), was one of the targets of miR‑1. Western blot assays showed that overexpression of miR‑1 significantly decreased the protein level of G6PD in pituitary tumor cells without changing the mRNA level of G6PD. Consequently, oxidative PPP flux analysis revealed that suppression of G6PD by miR‑1 decreased the production of nicotinamide adenine dinucleotide phosphate and the glycolysis of pituitary cancer cells. Restoration of the expression of G6PD significantly reversed the inhibitory effect of miR‑1 on the PPP and the growth of pituitary tumor cells. Collectively, the present results uncovered the critical involvement of miR‑1 in pituitary tumors, indicating that miR‑1 is a potential therapeutic target for the treatment of pituitary tumors.

17β-estradiol (E2) has been shown to have neuroprotective effects in different central nervous system diseases. The mechanisms underlying estrogen neuroprotection in spinal cord injury (SCI) remain unclear. Previous studies have shown that autophagy plays a crucial role in the course of nerve injury. In this study, we showed that E2 treatment improved the restoration of locomotor function and decreased the loss of motor neurons in SCI rats. Real-time PCR and western blot analysis revealed that the protective function of E2 was related to the suppression of LC3II and beclin-1 expression. Immunohistochemical study further confirmed that the immunoreactivity of LC3 in the motor neurons was down-regulated when treated with E2. In vitro studies demonstrated similar results that E2 pretreatment decreased the autophagic activity induced by rapamycin (autophagy sensitizer) and increased viability in a PC12 cell model. These results indicated that the neuroprotective effects of E2 in SCI are partly related to the suppression of excessive autophagy.

The regeneration of damaged or lost tissue is considered to be a critical step toward realizing full organ regeneration in modern medicine. Although surgical techniques continue to advance, treatment for missing tissues in irregular wounds remains particularly difficult. With increasing interest in the application of additive manufacturing in tissue engineering, the fabrication of customized scaffolds for the regeneration of missing tissue via three-dimensional (3D) printing has become especially promising. Amongst the work on the regeneration of many important organs, liver regeneration is particularly interesting because liver diseases are increasingly prevalent in many countries around the world, resulting in a greater need for liver transplantation. The generation of hexagonal scaffolds for the regeneration of liver lobules is highly demanding, but their 3D structure has been proved difficult to reproduce by traditional fabrication methods. In this work, various hexagonal scaffolds are developed for liver lobule regeneration via 3D printing using novel biodegradable polymeric materials, including poly(glycerol sebacate) acrylate and poly(ethylene glycol) diacrylate. Through fine-tuning of printing parameters, a series of hexagonal scaffolds were designed and printed to mimic liver lobule units. The scaffolds were printed with various structures together with varying surface areas and 3D structures to enhance cell seeding density and diffusivity of the culture medium. Analysis of cell metabolic activities showed that the high-diffusion staircase (HDS) scaffold could support potential differences in cell proliferation rate. Furthermore, the HDS scaffolds composed of different copolymers were cultured with cells for up to 16 days to investigate the relationship between physical properties and hepatocyte proliferation. The results indicate that the combination of the high flexibility 3D printing with biodegradable, photocurable copolymers shows great promise for the regeneration of 3D liver lobules.

Chondrosarcoma, a common malignant tumour, develops in bone. Effective adjuvant therapy remains inadequate for treatment, meaning poor prognosis. It is imperative to explore novel remedies. Angiogenesis is a rate-limiting step in progression that explains neovessel formation for blood supply in the tumour microenvironment. Numerous studies indicate that EPCs (endothelial progenitor cells) promote angiogenesis and contribute to tumour growth. bFGF (basic fibroblast growth factor), a secreted cytokine, regulates biological activity, including angiogenesis, and correlates with tumorigenesis. However, the role of bFGF in angiogenesis-related tumour progression by recruiting EPCs in human chondrosarcoma is rarely discussed. In the present study, we found that bFGF induced VEGF (vascular endothelial growth factor) expression via the FGFR1 (fibroblast growth factor receptor 1)/c-Src/p38/NF-κB (nuclear factor κB) signalling pathway in chondrosarcoma cells, thereby triggering angiogenesis of endothelial progenitor cells. Our in vivo data revealed that tumour-secreted bFGF promotes angiogenesis in both mouse plug and chick CAM (chorioallantoic membrane) assays. Xenograft mouse model data, due to bFGF-regulated angiogenesis, showed the bFGF regulates angiogenesis-linked tumour growth. Finally, bFGF was highly expressed in chondrosarcoma patients compared with normal cartilage, positively correlating with VEGF expression and tumour stage. The present study reveals a novel therapeutic target for chondrosarcoma progression.

Long noncoding RNA (lncRNA) MEG3 is an important tumor suppressor in several types of human cancers. However, the biological function and underlying mechanism of MEG3 in vascular endothelial cells (VECs) remain unknown. In the present study, we demonstrated the functional importance of lncRNA MEG3 in proliferation and angiogenesis of VECs. MEG3 overexpression significantly suppressed the proliferation and in vitro angiogenesis in VECs, whereas knockdown of MEG3 had the opposite effect. Furthermore, we found that MEG3 exerts its function through negatively regulating miR-9 by acting as a microRNA sponge. Taken together, MEG3-miR-9 plays an important role in proliferation and angiogenesis in VECs.

Taguchi Gen'ichi introduced Mahalanobis-Taguchi System (MTS) which is in combination with the concepts of quality engineering and Mahalanobis Distance (MD). The MTS is proposed as diagnosis and forecasting method using multivariate measurement scale with its intention to help policy maker as basis for decision making. This study applies MTS approach in a manufacturing process to reduce a set of parameters, at the same time there will be a pattern, which can forecast and identify important parameters, constructed by MTS method. Through this pattern can minimize unimportant inspection in process and save unnecessary time and cost. The primary goal to structure a measuring scale which makes accurate forecasting in multidimensional system. The case study in this paper reviews the planarity of back-end process in 8-inch silicon wafers on the purpose to construct a pattern of reduced set of parameters. In this paper, using thirty-two current variables as reference space and furthermore reducing the variables to seven parameters in order to predict defective items. As a result, it has still good discriminant accuracy. If validation of the reduced-set parameters is reliable with its good discriminant accuracy, it means that the company in this case study can built defective items warning of the pattern parameters in back-end process because this approach of selecting parameters is feasible.

Background/PurposeOur previous work has demonstrated that rat bone marrow stem cells (BMSCs) can transdifferentiate into α-amylase-producing cells after coculture with rat submandibular gland acinar cells. These transdifferentiated cells may be used for regeneration of damaged salivary gland. The purpose of this study was to investigate the global gene expression of rat BMSCs cocultured with rat submandibular gland acinar cells and the factors inducing this transdifferentiation.MethodsRat BMSCs were indirectly cocultured with rat submandibular gland acinar cells by using the double chamber system for 5 and 10 days. The global gene expression of BMSCs during transdifferentiation into acinar cells was investigated by microarray analysis.ResultsA total of 45,018 probes were used and 41,012 genes were detected. After coculture for 5 days, 1409 genes were upregulated more than twofold and 1417 genes were downregulated more than twofold (p

Based on the proppant index, a production forecast method for thick oil-bearing formation fracturing was deduced. And combined with NPV methodology, treatment scale of multistage pump-off propped fracturing can be optimized. The effects of treatment parameters, such as injection stages, pumping interval, pumping rate, the ratio of pre and post stage pumping rate, on the fracture geometry, conductivity and production were simulated and analyzed. It reveals that two injection stages, 5 minutes of pumping interval and consistent pumping rate contribute to the highest annual cumulative production. Moreover, the injection stages make the most significant influence on production. Optimization results, applied to Kunbei Oilfield, achieved satisfactory application effects. The single well average production was enhanced by7.92 t/d, the stimulation ratio was 13.56, and the stimulation validity was about 270 days.

Plant growth simulation models are valuable tools for optimizing the environmental factors and managing crop cultivation in cultural facilities. Researches presently on tomato simulation models have mainly focused on the plant growth and development, growth stages, dry matter production and distribution, however, no report on modeling of tomato fruit quality has been published yet. In this study, the method of accumulated Thermal Effectiveness and PAR (TEP) was employed to model the dynamic relationship between the major quality indicators and the environmental factors. Data of both indicators of tomato fruit quality and environmental factors, temperature and solar radiation of the cultivation environment, were collected under multiple protected structures like solar greenhouse and plastic tunnel for tomato production. The variety of simulation models were established based on the effects of temperature and solar radiation on tomato quality formation, and independently tested with the modeling data. The results show that the dynamic changes of the indicators of fruit quality after fruit set are accorded with the amount of accumulated TEP and individual indicators of fruit quality are suitable to its specific models. The fruit hardness is well accorded with a formula of generalized least squares FHi = k 1 + k 2 × TEPi + k 3 × TEPi 2 ; Fruit soluble sugar content is in a formula of Logistic model SSCi = b 1 1 + e b 2 + b 3 × TEPi . Fruit organic acid content is in a formula of generalized least squares OACi = n 1 + n 2 × TEPi + n 3 × TEPi 2 . Fruit tannin content is in a formula of Johnson Schumacher model TCi = q 1 × e - q 2 TEPi + q 3 . According to the established fruit hardness model, the determination coefficient R2 values based on the 1:1 beeline between the simulated values and the measured values of the first, second, third and the fourth truss of fruit are 0.9396, 0.9181, 0.8910 and 0.9523, respectively and values of root mean square error (RMSE) are 0.833 kg/cm2, 0.942 kg/cm2, 0.628 kg/cm2 and 0.738 kg/cm2, respectively. Based on the established fruit soluble sugar content model, the determination coefficient R2 values based on the 1:1 beeline between the simulated values and the measured values of the first, second, third and the fourth truss of fruit are 0.8596, 0.9420, 0.9027 and 0.9473, respectively and the values of RMSE are 1.011%, 0.710%, 0.771% and 0.608%, respectively. On the basis of the established fruit organic acid content model, the determination coefficient R2 values based on the 1:1 beeline between the simulated values and the measured values of the first, second, third and the fourth truss of fruit are 0.8856, 0.9025, 0.9183 and 0.8768, respectively and the values of RMSE are 0.029%, 0.030%, 0.024% and 0.023%, respectively. According to the established fruit tannin content model, the determination coefficient R2 values based on the 1:1 beeline between the simulated values and the measured values of the first, second, third and the fourth truss of fruit are 0.9481, 0.9219, 0.9521 and 0.8911, respectively and the values of RMSE are 13.41 mg/kg, 14.04 mg/kg, 13.92 mg/kg and 16.78 mg/kg, respectively. All of the coefficients of determination R2 are higher than 0.85, and the values of RMSE are generally smaller, which means the modeling is accurate and well accordance. This study will form a theoretic basis and provide technical support for the management of tomato production and environment control under plastic tunnel and solar greenhouse cultivation.

To study the influence of Radix aconiti lateralis preparata and Rhizoma zingiberis, two species of Chinese medicinal herbs with hot property, on energy metabolism and gene expression spectrum, and to analyze the possible mechanism of their effects.Forty-eight specific pathogen free Wistar rats were randomly divided into a Radix aconiti lateralis preparata group, a Rhizoma zingiberis group, and a control group. They were intragastrically treated with concentrated decoction of Radix aconiti lateralis preparata, Rhizoma zingiberis and normal saline respectively for 20 days. Toe temperature (TT), energy intake (EI), digestible energy (DE), and metabolizable energy (ME) were measured. The content of adenosine triphosphate (ATP) and energy charge (EC) in hepatic tissue were measured with high performance liquid chromatography (HPLC). The activity of ATPase and succinate dehydrogenase (SDH) in the liver were detected with chemical colorimetry. The gene expression in the liver was detected with Illumina's rat Ref-12 gene array. The differential expression genes were selected, annotated and classified based on Gene Ontology (GO). Real-time quantitative reverse-transcriptase PCR (Q-RT-PCR) was used to test the accuracy of results.Compared with the control group, the TT on the 10(th) day after the beginning of administration and ATP in the Radix aconiti lateralis preparata and Rhizoma zingiberis groups increased significantly (P0.05). EI/body mass (BM), DE/BM, ME/BM, the hepatic EC and the activity of Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase and SDH of liver increased significantly only in the Radix aconiti lateralis preparata group (P0.05). There were 592 differential expression genes in the Radix aconiti lateralis preparata group and 1 159 in the Rhizoma zingiberis group compared with the control group. Among the differential expression genes, genes related to metabolic processes were the most significant based on GO analysis. There were 337 strips of gene differential expression in common in both Radix aconiti lateralis preparata and Rhizoma zingiberis groups compared with the control group.Herbs with hot property such as Radix aconiti lateralis preparata and Rhizoma zingiberis could improve the energy metabolism in rats, through influencing the metabolic process of sugar, lipid, and amino acid. It could also promote the production, storage, and utilization of energy by regulating the gene expression related to metabolism, which may be the main molecular mechanism of warming yang and dispelling cold for the treatment of the cold syndrome according to Chinese medicine theory.

Chitosanase is an enzyme that hydrolyzes chitosan, a β-(1–4) glucosamine polymer, into size-specific oligomers that have pharmaceutical and biological properties. The aim of the present work was to use the bipolar membrane technology, in particular the OH− stream produced by water splitting, for inactivation of chitosanase at alkaline pH in order to terminate the enzymatic reaction producing chitosan oligomers. The objectives consisted of studying the effect of pH: (a) on the stability of chitosanase, and (b) on the catalytic activity of chitosanase during chitosan hydrolysis. The enzyme was found to be stable in the pH range of 3–8 during at least 7 h, and partially lost its activity after 1 h at pH 8. The catalytic activity of chitosanase during chitosan hydrolysis decreased after pH adjustment by electrobasification. The reaction rate decreased by 50% from pH 5.5 to 6, whereas the reaction was completely inhibited at pH > 7. The decrease of reaction rate was due to chitosan substrate insolubilization and chitosanase denaturation at alkaline pH values.

Hemophagocytic syndrome (HPS) may be primary or secondary to malignancies, infections, autoimmune diseases, or drugs. In most cases, HPS occurs at the same time as the diagnosis of underlying malignancy or when it relapses. In rare situations, the neoplastic disease can be occult, even for more than a decade. We report the case of a 28-year-old woman admitted because of HPS. Treatment with etoposide for fulminant HPS was effective. Four months later, she was admitted again because of newly developed subcutaneous nodules and cellulitis-like skin lesions over her legs. Excisional biopsy of subcutaneous nodule showed subcutaneous panniculitis-like T-cell lymphoma. After etoposide, solumedrol, cytosine arabinoside, and cisplatin regimen chemotherapy, both skin lesions and subcutaneous nodules disappeared. In conclusion, for patients presenting with HPS and cellulitis-like skin lesions, occult lymphoma should be considered, which might not be diagnosed for months, even years. Adequate treatment, including steroid and chemotherapy against malignant lymphoma, should be started as soon as possible for patients with fulminant HPS because of its fatal course. [ J Formos Med Assoc 2007;106(2 Suppl):S55-S59]

Large intergenic long noncoding RNA p21 (lincRNA-p21) has recently shown to play an important role in biological functions. However, the biological role of lincRNA-p21 in vascular endothelial cells remains unclear. In the present study, we investigated the role of lincRNA-p21 in vascular endothelial cells through gain- and loss-of-function studies and found that lincRNA-p21 promoted cell apoptosis and induced cell cycle progression. Furthermore, lincRNA-p21 acted as an endogenous sponge by directly binding to miR-130b and decreased miR-130b expression. In addition, miR-130b reversed the inhibitory effect of lincRNA-p21 on the growth of vascular endothelial cells. Taken together, our data highlight the pivotal role of lincRNA-p21 in the growth of vascular endothelial cells.

and 4 surface swabs from the furniture and equipments within the ICU. All isolates, including those from patients, demonstrated identical PFGE patterns. The colonization of C. indologenes on a plastic pipe attached to the tap in the washing room may have led to the subsequent contamination of the ICU environment. On-site inspection also found that hand hygiene policy and infection control measures were not adequately implemented. Re-education of the personnel, removal of the contaminated water pipe, and daily cleaning of the environment with hypochlorite solutions successfully stopped the outbreak. Conclusions: The significant increase of C. indologenes HAI in the ICU was an outbreak probably originated from a contaminated water pipe used to clean sputum suction bottles. On-site inspection and intervention as well as the molecular typing analysis provided solid evidence and helped to terminate the outbreak.

Amyloid plaque is the hallmark and primary cause of Alzheimer disease. Mutations of presenilin-1, the gamma-secretase catalytic subunit, can affect amyloid-beta (Abeta) production and Alzheimer disease pathogenesis. However, it is largely unknown whether and how gamma-secretase activity and amyloid plaque formation are regulated by environmental factors such as stress, which is mediated by receptors including beta(2)-adrenergic receptor (beta(2)-AR). Here we report that activation of beta(2)-AR enhanced gamma-secretase activity and thus Abeta production. This enhancement involved the association of beta(2)-AR with presenilin-1 and required agonist-induced endocytosis of beta(2)-AR and subsequent trafficking of gamma-secretase to late endosomes and lysosomes, where Abeta production was elevated. Similar effects were observed after activation of delta-opioid receptor. Furthermore, chronic treatment with beta(2)-AR agonists increased cerebral amyloid plaques in an Alzheimer disease mouse model. Thus, beta(2)-AR activation can stimulate gamma-secretase activity and amyloid plaque formation, which suggests that abnormal activation of beta(2)-AR might contribute to Abeta accumulation in Alzheimer disease pathogenesis.

Background: Angiogenesis has been extensively studied in acute myeloid leukemia (AML). Lactate dehydrogenase (LDH), a common biochemical marker for tumor burden and anaerobic glycolysis, is a poor prognostic factor for AML. Regulated by hypoxia-induced factor, both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are responsive to cancer-related angiogenesis. To study the roles of serum LDH, VEGF and bFGF in AML angiogenesis, we investigated bone marrow vascularity in untreated AML patients, and analyzed its relationship to serum LDH, VEGF and bFGF levels. Methods: Eighteen (11 males, 7 females; mean age, 57.7 years) de novo, untreated AML patients were enrolled. Bone marrow vascularity was evaluated by staining bone marrow core biopsy tissue with endothelial cell marker CD31 or CD34. Serum LDH was determined with the Wroblewski-La Due method. Serum VEGF and bFGF were determined with enzyme-linked immunoassay. The relationship of LDH, VEGF and bFGF level to bone marrow vessel numbers was examined by linear regression. Results: Log LDH significantly correlated to AML bone marrow vascularity (r = 0.61; p = 0.007). VEGF and bFGF concentrations did not correlate with AML angiogenesis. Conclusion: These results suggest that serum LDH, but not VEGF and bFGF concentrations, can be used as a simple parameter for predicting vessel formation in AML bone marrow. [J Chin Med Assoc 2006;69(11):534–537]

Eosinophilic myocarditis is recognized by severe heart failure and marked eosinophilia infiltration resulting from different etiologies. Acute necrotizing eosinophilic myocarditis, the initial presentation of the disease, is rare and often fatal, with unique echocardiographic pictures, and followed by endocardial thrombosis and chronic endomyocardial fibrosis. We report a young female with acute lymphoblastic leukemia who presented fever and acute heart failure syndrome. The echocardiography showed severe left ventricle diastolic dysfunction with preserved ejection fraction. Systemic eosinophilia and the unique echocardiographic images made the diagnosis of acute necrotizing eosinophilic myocarditis. The patient survived after intensive cytotoxic chemotherapy including high-dose steroid.

Dear Editor, T-cell non-Hodgkin’s lymphomas (NHLs) are a group of heterogeneous diseases with more aggressive behavior and dismal outcome than B-cell NHLs and account for less than 10% of the cases of aggressive NHLs in Western countries [1]. The outcome of T-cell NHL is even worse when it occurs in combination with hemophagocytic lymphohistiocytosis (HLH); this combination presents with fever, cytopenia, liver dysfunction, hepatosplenomegaly, hypertriglyceridemia, and hyperferritinemia [2, 3]. We report the case of a patient who had angioimmunoblastic T-cell lymphoma (AITL) and HLH and was successfully treated by allogeneic hematopoietic stem cell transplant (HSCT) with a reduced-intensity conditioning (RIC) regimen. The patient was a 62-year-old woman who did not have any other systemic diseases and presented with fever of up to 38.5°C of 1-week duration; she lost 20 kg in 6 months as well. Physical examination showed neck lymph node enlargement and hepatosplenomegaly. Abdominal computed tomography showed hepatosplenomegaly and retroperitoneal lymphadenopathy. Cervical lymph node biopsy was performed and the biopsy specimen showed heterogeneous infiltration of medium-sized atypical lymphocytes, with proliferation of post-capillary venules (Fig. 1a) and features of hemophagocytosis (Fig. 1b); it was immunohistochemically positive for CD3 and CD4, but negative for CD8, CD30, CD56, and CD20. AITL was diagnosed on the basis of these biopsy results. In situ hybridization detected Epstein–Barr virus-encoded RNA. Bone marrow examination showed prominent hemophagocytosis, but without evidence of lymphoma involvement. The patient had normal prothrombin time, activated partial thromboplastin time, fibrinogen levels, and liver and renal functions. However, the presence of anemia (hemoglobin 8.4 gdl, reference range 12–14), hyperferritinemia (ferritin 26,400 μg l, reference range 10– 120), elevated lactate dehydrogenase (673 Ul, reference range 120–240), hypertriglyceridemia (triglyceride 278 mg dl, reference range

The construction of different types of substituted arenes was demonstrated through the photocyclization of 2-(fur-3-yl)ethenylarenes using a 3-furyl group as an isopropenyl equivalent synthon in the photocyclization reaction. The furan portion of the photocyclization intermediate could be fragmented via a base-induced elimination reaction to yield a series of substituted polyaromatics, including naphthalene, benzofuran, benzothiophene, phenanthrene, phenalene, acenaphthene, and triphenylene. Using different reagents, this method made it possible to introduce methyl or 2-hydroxyethyl groups as substituents at specific positions in these arenes.

Crustacean shells constitute the traditional and current commercial source of chitin. Conversely, the control of fungal fermentation processes to produce quality chitin makes fungal mycelia an attractive alternative source. Therefore, the exploitation of both of these sources to produce chitin in a concurrent process should be advantageous and is reported here. Three proteolytic Aspergillus niger (strains 0576, 0307 and 0474) were selected from a screening for protease activity from among 34 zygomycete and deuteromycete strains. When fungi and shrimp shell powder were combined in a single reactor, the release of protease by the fungi facilitated the deproteinization of shrimp-shell powder and the release of hydrolyzed proteins. The hydrolyzed proteins in turn were utilized as a nitrogen source for fungal growth, leading to a lowering of the pH of the fermentation medium, thereby further enhancing the demineralization of the shrimp-shell powder. The shrimp-shell powders and fungal mycelia were separated after fermentation and extracted for chitin with 5% LiCl/DMAc solvent. Chitin isolates from the shells were found to have a protein content of less than 5%, while chitin isolates from the three fungal mycelia strains had protein content in the range of 10-15%. The relative molecular weights as estimated by GPC for all chitin samples were in the 10(5) dalton range. All samples displayed characteristic profiles for chitin in their FTIR and solid-state NMR spectra. All chitin samples evaluated with MTT and Neutral Red assays with three commercial cell lines did not display cytotoxic effects.

Because glycine plays a prominent role in living creatures, an accurate and precise quantitative analysis method for the compound is needed. Herein, a new approach to analyze glycine by hydrophilic interaction chromatography (HILIC) coupled with electrospray ionization tandem mass spectrometry (ESI-MS/MS) was developed. This method avoids the use of derivatization and/or ion-pairing reagents. N-methyl- d -aspartate (NMDA) is used as the internal standard (IS). The mobile phase for the isocratic elution consisted of 10 mM ammonium formate in acetonitrile–water (70:30, v/v, adjusted to pH 2.8 with formic acid), and a flow rate of 250 μL/min was used. Two microliters of sample was injected for analysis. The signal was monitored in the positive multiple reaction monitoring (MRM) mode. The total run time was 5 min. The dynamic range was 40–2000 ng/mL for glycine in the biological matrix. The LLOQ (lower limit of quantification) of this method was 40 ng/mL (80 pg on column). The validated method was applied to determine the dynamic release of glycine from P19 embryonal carcinoma stem cells (ECSCs). Glycine spontaneously released from the ECSCs into the intercellular space gradually increased from 331.02 ± 60.36 ng/mL at 2 min in the beginning to 963.52 ± 283.80 ng/mL at 60 min and 948.27 ± 235.09 ng/mL at 120 min, finally reaching a plateau, indicating that ECSCs consecutively release glycine until achieving equilibration between the release and the reuptake of the compound; on the contrary, the negative control NIH/3T3 embryonic fibroblast cells did not release glycine. This finding will help to improve our understanding of the novel effects of neurotransmitters, including glycine, on non-neural systems.

Multiple organ dysfunction syndrome (MODS) is an important cause of morbidity and mortality in intensive care unit. A severe insult in the form of infection or trauma primes the host immune system so that a subsequent, relatively trivial insult produces systemic inflammation response syndrome, which can lead to MODS and death. Matrix metalloproteinase-9 (MMP-9) is stored in the tertiary granules of polymorphonuclear leukocytes. These cells are key effectors in acute inflammatory diseases, such as sepsis and MODS. Endotoxin leads to rapid release of MMP-9 from these granules in vitro and in vivo. However, the role of this enzyme in MODS, and whether it is associated with organ injury at the early stage of MODS remains unclear. This present work may study role of MMP-9 with the MODS rats that caused by trauma and infection and investigate the mechanism of organ injury at the early stage of MODS. Here, we developed a rat model for MODS caused by trauma and infection and analyzed the dynamic level of MMP-9 and determined the relationship between MMP-9 level and early phase of organ injury in MODS rat. The histological changes in pulmonary, renal, and hepatic tissue were observed by light microscope. The expressions of plasma MMP-9 proteins were detected by an enzyme linked immunosorbent assay and its levels in the pulmonary, renal, and hepatic tissue were detected by using immunohistochemistry, respectively. The results indicated that there were no significant improvements in histopathology of rats in control group. However, the pulmonary, renal, and hepatic damage were serious in MODS groups. The concentration of MMP-9 in plasma and tissues of MODS rats increased markedly at the early stage and were higher than that of the control group. Moreover, the MMP-9 level in plasma positively correlated with the levels of pulmonary, renal, and hepatic tissue. This study clearly shows that MMP-9 is good biomarker to predict the severity of injury organ at the early phase of MODS.

Hemophagocytic lymphohistiocytosis (HLH), presenting with fever, cytopenia, liver dysfunction, hepatosplenomegaly, hypertriglyceridemia, and hyperferritinemia, is associated with various etiologies, including infections, collagen vascular diseases, and malignancies. The present report describes a 28-year-old woman who developed HLH combined with autoimmune hemolytic anemia (AIHA) at 23 weeks of gestation. Without response to corticosteroid, the patient completely recovered from both HLH and AIHA after termination of the pregnancy. Pregnancy-induced immune dysregulation and cytokine overproduction in genetically susceptible women may play critical roles in HLH. The differential diagnosis of pregnant women with fever and cytopenia should include HLH. Pregnancy termination should be considered when pregnancy-induced HLH is refractory to medical treatment.

Here, we report an unusual case of gastric anaplastic large cell lymphoma (ALCL), lymphohistiocytic variant, in a 70-year-old female patient who presented with epigastric pain, tarry stool and body weight loss. Endoscopic and imaging findings revealed a Bormann type II tumor in the stomach with perigastric lymphadenopathy and multiple tumor nodules in the liver. Total gastrectomy and liver biopsy were performed. Histologically, both gastric and hepatic tumors demonstrated anaplastic large neoplastic cells scattered among numerous reactive histiocytes. Immunostaining of these tumor cells reacted positively for CD30, CD3, CD45 RO/UCHL1, and negatively for epithelial membrane antigen, CD68, lysozyme, CD15, CD79a, CD138, PAX5 and anaplastic lymphoma kinase. Both the morphologic and immunophenotypic findings supported the diagnosis of gastric ALCL of lymphohistiocytic variant with liver metastasis. This patient then received chemotherapy and was still alive after 17 months of follow-up, without evidence of residual disease.

Takayasu’s arteritis (TA) is a vasculitis characterized by inflammation and obliteration of intermediate to large-size arteries. We report a case of Takayasu’s arteritis with a presentation of bilateral pulmonary nodular infiltrates in a 21-year-old man. An open-lung biopsy showed characteristic changes of extra-vascular granulomatosis. To our knowledge, this has not been described previously in the literature.

Dear Editor, Hepatitis B virus (HBV) reactivation is a serious problem for patients with malignancy when receiving cytotoxic chemotherapy, especially for lymphoma patients [1]. Pei et al. [2] demonstrate that Rituximab-based chemotherapy regimen increases risk of HBV reactivation. For patients with positive HBV surface antigen (HBsAg), the consensus in Taiwan is prophylaxis with anti-HBV drugs during and 3 to 6 months after chemotherapy. With more evidence for use of Rituximab in 2-year maintenance therapy for follicular lymphoma [3] and for further treatment of diffused large B cell lymphoma, it remains unclear whether HBV prophylaxis during Rituximab maintenance therapy is indicated. Here, we present a 41-year-old woman with nonHodgkin's lymphoma (NHL) who died of HBV reactivation during Rituximab maintenance therapy. This patient was diagnosed as NHL, diffused large B cell stage IV, with initial presentation of abdominal fullness. Because of positive HBsAg, she received Lamivudine 100 mg per day during her six cycles of R-CHOP regimen (375 mg/M Rituximab, 750 mg/M cyclophosphamide, 50 mg/M Adriamycin, 1.4 mg/M vincristine, and 40 mg/ M prednisolone for 5 days). She achieved complete remission after this full course of chemotherapy, as shown by negative image findings of computer tomography and positron emission tomography. This patient received lamivudine daily for another 6 months after chemotherapy. She then entered a clinical trial of Rituximab maintenance therapy with schedule of 375 mg/M every 2 months for 2 years. Unfortunately, she suffered from reactivation of HBV, and fulminant hepatitis about 30 days after the ninth treatment with Rituximab. Her liver function is shown in Fig. 1. The patient's HBV DNA was 8.87×10 IU. There were no detectable mutations. We shifted her anti-HBV drug to Entecavir 1 mg per day, but she was not responsive. This patient eventually died of fulminant hepatitis. Rituximab-induced profound hypogammaglobulinemia and impaired humoral immune response have been demonstrated and might be responsible for HBV reactivation [4,5]. There is no consensus of HBV prophylaxis during Rituximab single therapy because only a few cases of HBV reactivation are reported [6,7]. Even if it is highly effective [8], one of the serious problems of HBV prophylaxis with lamivudine comes from its high resistance, which is about 25% annually [9]. For those receiving long-term Rituximab therapy, Entecavir may be a better option because it has minimal resistance rate after 5-years of use in patients with chronic hepatitis B [10]. C.-H. Cho :W.-L. Hwang :C.-L. Teng (*) Division of Hematology/Oncology, Department of Medicine, Taichung Veterans General Hospital, 160, Section 3, Chungkang Road, Taichung 407, Taiwan e-mail: drteng@vghtc.gov.tw

Dear Editor, We report a patient of monoclonal gammopathy of undetermined significance (MGUS) with manifestation of pyoderma gangrenosum refractory to steroids and chemotherapy. Both the M-protein and pyoderma gangrenosum disappeared after autologous peripheral blood stem cell transplantation (PBSCT). A 33-year-old man suffered from rapidly enlarging pustular papules and plagues that ulcerated the necrotic base over his left leg 5 years ago (Fig. 1a). His serum immunoelectrophoresis revealed IgA-λ monoclonal gammopathy (IgA 782 mg/dL, normal 70–400 mg/dL; κ/λ 1.17, normal 1.35–2.69). Bone marrow examination disclosed slight plasmacytosis, which was less than 10% of all the nucleated cells (Fig. 1b). Without anemia (hemoglobin, 12.7 mg/dl; normal, 12–14 mg/dl), thrombocytopenia (platelet count, 426×10/l; normal, 150–430×10/l), osteolytic lesions, and impaired renal function, he was diagnosed as MGUS, IgA-λ, complicated with pyoderma gangrenosum. The patient was initially treated with methylprednisolone pulse therapy, but the response duration was short. He was then treated as having myeloma, but neither thalidomide nor chemotherapy with vincristine, Adriamycin, and Decadron regimen (VAD) was effective. High-dose cyclophosphamide (4 g/M) was given, and his peripheral blood hematopoietic stem cells were collected. Consequently, he received autologous PBSCT with 6.5×10/kg CD34+ cells infusion. Conditioning regimen included total body irradiation (6 Gy) and melphalan (140 mg/M). After the PBSCT, his skin has been free of lesions for 18 months (Fig. 1c). Serum immunoelectrophoresis could not detect the IgA-λ M-protein either. As a pre-malignant plasma cell proliferative disorder, MGUS has a lifelong risk of progression to multiple myeloma [1]. Different from those with myeloma, patients with MGUS have less than 10% plasma cells in bone marrow and do not require any treatment [2]. Various kinds of skin disorders have been associated with monoclonal gammopathy [3]. Some of these dermatologic disorders directly relate to the malignant plasma cells infiltration, but some are associated with the Mprotein. It is uncommon, however, that patients with MGUS manifest severe dermatologic diseases, especially pyoderma gangrenosum. A study from Mayo Clinic shows that nine of 86 patients with pyoderma gangrenosum had monoclonal gammopathy and seven had IgA [4]. Demitsu et al. report a patient of IgA MGUS-related neutrophilic, urticaria-like C.-M. Chang :W.-L. Hwang : C.-L. Teng (*) Division of Hematology/Oncology, Department of Medicine, Taichung Veterans General Hospital, 160, Section 3, Chungkang Road, Taichung 407( Taiwan, Republic of China e-mail: drteng@vghtc.gov.tw

Primary splenic lymphoma (PSL) is a rare disease with ambiguous definition, comprising less than 1% of non-Hodgkin's lymphoma. Even rarer is PSL combined with hemophagocytic lymphohistiocytosis (HLH), which has presentations of fever, cytopenia, hepatosplenomegaly, hyperferritinemia, and phagocytosis of hematopoietic cells in the reticuloendothe-lial system. We report the case of a 77-year-old man who presented with HLH initially. Refusing diagnostic splenectomy, he received chemotherapy. Spontaneous splenic rupture occurred after chemotherapy. In the following emergency operation, PSL was diagnosed. He received another 5 courses of chemotherapy with the R-CNOP regimen (rituximab, cyclophosphamide, mitoxantrone, vincristine, prednisolone). Now he has no residual or relapsed disease. Diagnostic splenectomy for adult HLH patients without definite etiologies may play an important role. [J Chin Med Assoc 2008;71(4):210–213]