A test strip electrochemical disposable by 3D MXA/AuNPs DNA-circuit for the detection of miRNAs.

The simple and reliable detection of microRNAs is of great significance for studying the biological functions, molecular diagnosis, disease treatment and targeted drug therapy of microRNA. In this study, we introduced a novel Ti3C2Tx (MXene) aerogels (denoted as MXA) composite gold nano-particles (AuNPs)-modified disposable carbon fiber paper (CFP) electrode for the label-free and sensitive detection of miRNA-155. Firstly, in the presence of MXene, graphene oxide (GO) and ethylenediamine (EDA), the 3D MXene hydrogel was formed by self-assembly method, and then adding the freeze-dried 3D MXA dropwise to CFP. Subsequently, electrodepositing AuNPs on the CFP/MXA was done to construct a 3D disposable DNA-circuit test strip with excellent interface. Under the optimum experimental conditions, the detection limit of 3D disposable DNA circuit strip for miRNA-155 was 136 aM (S/N = 3). The CFP/MXA/AuNPs (CMA) electrode also has a wide dynamic range (20 fM to 0.4 µM), with a span of 4 orders of magnitude. Notably, we also tested the practicality of the sensor in 8 clinical samples. The technological innovations in the detection and quantification of microRNA in this work may be helpful to the study new aspects of microRNA biology and the development of diagnosis.

FGFR4 provides the conduit to facilitate FGF19 signaling in breast cancer progression.

Although genetic amplification and overexpression of the fibroblast growth factor 19 (FGF19) gene are found in human breast cancer, mechanisms that contribute to such functional alterations remain elusive. We report here that high expression of FGF19 is associated with the aggressive malignant behavior and poor survival outcome of breast cancer patients. FGF19 is particularly highly expressed in luminal molecular subtype of breast tumors and its expression levels are positively associated with its secretion levels from breast cancer cells. Genetic knockout of FGF19 significantly induces repression of breast tumor progression and metastasis in either an orthotopic mouse model of breast cancer or an experimental metastasis model. The FGF19 specific receptor, FGFR4, can be activated and subsequently upregulate AKT signaling in breast cancer cell upon FGF19, which is critical for oncogenic role of FGF19. Inactivation of FGFR4 by its inhibitor BLU9931 significantly attenuates FGF19-induced tumor-promoting activity, suggesting interruption of FGFR4 function is sufficient to affect FGF19-driven breast cancer. Overall, these insights support the idea that targeting FGFR4 in breast cancer cells overexpressing FGF19 may represent an effective strategy to suppress cancer development, progression, and metastasis.

Survival benefit of pure dose-dense chemotherapy in breast cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Dose-dense chemotherapy is a widely accepted regimen for high-risk breast cancer patients. However, conflicting survival benefits of pure dose-dense chemotherapy have been reported in different randomized controlled trials (RCTs). This meta-analysis aimed to further assess the efficacy and safety of pure dose-dense chemotherapy in breast cancer. METHODS: A literature search of electronic databases and websites was performed to identify phase III RCTs reporting the efficacy and toxicity of pure dose-dense chemotherapy. The endpoints of interest were overall survival (OS), disease-free survival (DFS), and toxicities. The hazard ratios (HRs) of death and recurrence and the odds ratios (ORs) of adverse events were estimated and pooled. RESULTS: Seven studies (five trials) were eligible, encompassing a total of 9851 patients. Patients treated with dose-dense chemotherapy obtained better DFS (HR = 0.83; 95% CI 0.75-0.91; p = 0.0001) than those treated with the conventional schedule, while OS benefit of dose-dense chemotherapy was less impressive (HR = 0.86; 95% CI 0.73-1.02; p = 0.08). However, significant OS benefit was observed in node-positive patients (HR = 0.77; 95% CI 0.66-0.90; p = 0.001). The incidence of anemia, pain, and transaminase elevation was higher in the dose-dense chemotherapy arm. CONCLUSIONS: Dose-dense chemotherapy leads to better prognosis; these findings suggest that it may be a potentially preferred treatment for breast cancer patients, particularly for women with lymph node involvement. However, more RCTs are warranted to better define the best candidates for dose-dense chemotherapy.

[Mutation analysis of the PAH gene in children with phenylketonuria from the Qinghai area of China].

OBJECTIVE: To study the mutation characteristics of the phenylalanine hydroxylase (PAH) gene in children with phenylketonuria (PKU) from the Qinghai area of China, in order to provide basic information for genetic counseling and prenatal diagnosis. METHODS: Mutations of the PAH gene were detected in the promoter and exons 1-13 and their flanking intronic sequences of PAH gene by PCR and DNA sequencing in 49 children with PKU and their parents from the Qinghai area of China. RESULTS: A total of 30 different mutations were detected in 80 out of 98 mutant alleles (82%), including 19 missense (63%), 5 nonsense (17%), 3 splice-site (10%) and 3 deletions (10%). Most mutations were detected in exons 3, 6, 7, 11 and intron 4 of PAH gene. The most frequent mutations were p.R243Q (19%), IVS4-1G>A (9%), p.Y356X (7%) and p.EX6-96A>G(5%). Two novel mutations p.N93fsX5 (c.279-282delCATC) and p.G171E (c.512G>A) were found. p.H64fsX9(c.190delC) was documented for the second time in Chinese PAH gene. The mutation spectrum of the gene PAH in the Qinghai population was similar to that in other populations in North China while significantly different from that in the populations from some provinces in southern China, Japan and Europe. CONCLUSIONS: The mutations of PAH gene in the Qinghai area of China demonstrate a unique diversity, complexity and specificity.

An ultrasensitive and point-of-care sensor for the telomerase activity detection.

Telomerase owns great application potential in diagnosis, therapy, prognosis, and drug screening of cancers. Thus, the ultrasensitive and point-of-care detection of telomerase activity meets the clinical demands extremely. Here, a sensor based on telomerase extends activators to unlock the ssDNase activity of CRISPR/Cas12a was created for the first time to detect the telomerase activity. Based on the fluorescence or CRISPR/Cas12a-based lateral flow assay, we achieve the ultrasensitive and point-of-care detection of telomerase activity in MCF-7 cells low to 57 cells·mL-1 and 5.7 × 102 cells·mL-1 in about 1 h, respectively. Besides, the detection of telomerase activity in different subtype breast cancer cells indicates that the proposed sensor possesses potential in the classification of breast cancer cell subtypes.

Naked-eye detection of site-specific ssRNA and ssDNA using PAMmer-assisted CRISPR/Cas9 coupling with exponential amplification reaction.

Accurate and effective detection of single-stranded nucleic acids is vital in both disease diagnosis and pathological studies. Hence, we develop a PAMmer-assisted CRISPR/Cas9 system mediated G4-EXPAR (Cas-G4EX) strategy for site-specific detection of ssRNA and ssDNA. PAMmer-assisted CRISPR/Cas9 executes the site-specific cleavage of target ssRNA or ssDNA and released product fragment with the desired sequence at the 3'-terminal. This fragment serves as a primer to activate subsequent sequence-dependent exponential amplification reaction (EXPAR). The G-rich EXPAR products assembles with hemin to form a G-Quadruplex (G4/hemin). G4/hemin catalyzes ABTS-H2O2 system with the appearance of vivid green color, realizing naked-eye analysis. Cas-G4EX integrates the superiority of CRISPR/Cas9 and EXPAR, presenting outstanding site-specific recognition and high-performance amplification efficiency. Meanwhile, the programmability of CRISPR/Cas9 system makes the proposed method become a universal detection paradigm for any ssRNA or ssDNA. Cas-G4EX assay shows the linear relationship from 250 aM to 2.5 nM for ssRNA detection with the actual LOD of 250 aM, and that ranges from 100 aM to 1 nM for ssDNA detection with the actual LOD of 100 aM. Additionally, the acceptable recoveries of 101.48%-109.61% for ssRNA and 93.25%-111.98% for ssDNA in real detection of human serum are obtained for detection of single-strand nucleic acid in real samples. Cas-G4EX also exhibits the excellent discrimination for single-base mutation of single-stranded nucleic acids. Therefore, Cas-G4EX assay provides a promising platform in the applications of molecular diagnosis and pathological analysis.

A Methodology for Ultrasensitive Detection of Sequence-Specific DNA or Uracil-DNA Glycosylase Activity.

Ultrasensitive detection of sequence-specific DNA and uracil-DNA glycosylase (UDG) activity shows great practical significance in clinical diagnostic and biomedical studies. Here, a methodology based on a CRISPR/Cas12a system coupled with enhanced strand displacement amplification (E-SDA) was innovatively established for sequence-specific DNA or UDG activity detection. Sequence-specific DNA or DNA primers processed by UDG and Endonuclease IV can initiate E-SDA, generating auxiliary DNA chains, which act as activators to unlock the indiscriminate collateral cleavage activities (trans-cleavage) of the CRISPR/Cas12a. Then, the activated CRISPR/Cas12a, which intrinsically possesses the ability of significant signal amplification, can indiscriminately cleave the added cleavage reporters in the system. Thus, the multistep amplification of the method was obtained. Under the selected experimental conditions, the established method can achieve an actual sensitivity of sequence-specific DNA up to 100 aM within 2.5 h or ultralow UDG activity (3.1×10-5 U/mL) detection within 3.5 h. We believe that the proposed method will have great potential for practical application in ultrasensitive detection of sequence-specific DNA or UDG activity.

Terminal deoxynucleotidyl transferase induced activators to unlock the trans-cleavage of CRISPR/Cpf 1 (TdT-IU- CRISPR/Cpf 1): An ultrasensitive biosensor for Dam MTase activity detection.

DNA adenine methylation methyltransferase (Dam MTase) plays an important role in gene expression and cell development, and involves in some development of tumors. There are many methods to detect Dam MTase activity, yet they have some shortcomings such as high cost, limited detection limit and complicated operation. Here, a new fast and simple multiple amplification strategy based on terminal deoxynucleotidyl transferase induced activators to unlock the collateral cleavage activities (trans-cleavage) of CRISPR/Cpf 1 (TdT-IU-CRISPR/Cpf 1) was firstly established. Based on this, a new fluorescent biosensor for Dam MTase activity detection was proposed. Importantly, the proposed biosensor does not require strict control over the temperature changes, and has ultrasensitive detection with limit of detection as low as 1.26 × 10-3 U/mL. Moreover, the novel biosensor can not only be applied for screening the inhibitors for Dam MTase activity, but also can detect its activity in complex biological samples. The newly established multiple amplification strategy TdT-IU-CRISPR/Cpf 1 and the proposed biosensor for Dam MTase activity will be of great significance in biomedical testing and clinical diagnostics.

Up-regulation of IRAK-M is essential for endotoxin tolerance induced by a low dose of lipopolysaccharide in Kupffer cells.

BACKGROUND: Endotoxin tolerance (ET) is an important mechanism to maintain the homeostasis of Kupffer cells (KCs), because KCs are continually exposed to various pathogen-associated molecular patterns including lipopolysaccharide (LPS). ET involves multiple changes in cell signal transduction pathways; however, not all signaling pathways are down-regulated and some proteins are up-regulated. The latter proteins may be counter regulatory, including interleukin-1 receptor-associated kinase M (IRAK-M) expression. The aim of this study is to clarify weather or not IRAK-M is involved in the mechanisms of ET in KCs through dampening nuclear factor-kappa B (NF-kappaB) mediated pathway. MATERIALS AND METHODS: KCs isolated from male C57BL/6J mice were seeded in 24-well plates at 1 x 10(6) cells/well and cultured overnight prior to transfection, were randomly divided into two groups: the pIRAK-M-short hairpin RNA (shRNA) group (transfected with IRAK-M shRNA) and the control group (transfected with control vector); 24 h after transfection, the two groups were further randomly divided into two subgroups: non-endotoxin pretreatment group (incubation in Dulbecco's modified Eagle's medium [Invitrogen, Carlsbad, CA] with 10% fetal bovine serum) and endotoxin pretreatment group (incubation in the same medium containing 10 ng/mL LPS), named pIRAK-M-EP, pIRAK-M-NEP, pCV-EP, and pCV-NEP, respectively. Each subgroup contained 6 wells; 24 h later, fresh media containing LPS (100 ng/mL) was added to each subgroup and incubated for an additional 3 h. The expression of IRAK-M gene and protein level were determined by reverse transcription-polymerase chain reaction and Western blot, the activities of NF-kappaB were estimated by electrophoretic mobility shift assay and enzyme-linked immunosorbent assay, and the supernatant tumor necrosis factor-alpha levels were analyzed by enzyme-linked immunosorbent assay. RESULTS: The recombinant plasmid of pIRAK-M-shRNA specifically inhibited IRAK-M expression after it was transfected into KCs. At 3 h after 100 ng/mL LPS was added to the medium, IRAK-M expression was significantly induced in pCV-EP than that in pCV-NEP; however, there was no difference between pIRAK-M-NEP and pIRAK-M-EP, accompanied with lowest level of NF-kappaB activation and tumor necrosis factor-alpha levels in pCV-EP, and a dramatic enhancement in the other three groups (P < 0.01). CONCLUSIONS: Although a primary low dose of LPS stimulation obviously attenuated KCs response to the second LPS stimulation, the inhibitive influences were partly refracted in pIRAK-M-EP than in pCV-EP, indicating that the absence of IRAK-M caused abnormal enhancement of inflammatory effects. IRAK-M negatively regulates toll-like receptors signaling and involves in the mechanisms of ET in KCs through dampening NF-kappaB mediated pathway; therefore it may be a key component of this important control system, and a new target for the clinical treatment of sepsis.

[Heterogeneity changes in secretion ability of monocyte/macrophage and its significance after trauma hemorrhage in rat].

OBJECTIVE: To investigate the relationship between the heterogeneity in secretion ability of monocyte (Mo)/macrophage and the immune dysfunction after severe trauma. METHODS: Twenty-four healthy Wistar rats were randomly divided into normal control group and trauma hemorrhage 1, 4 and 7 days groups. The contents of interleukin-6 (IL-6) and IL-10 secretion of Mo/macrophage from different anatomical regions were determined by radioimmunoassay. RESULTS: (1)In normal rats, the ability to secrete IL-6 and IL-10 was different among alveolar macrophages (AM), peritoneal macrophages (PM) and Mo. PM showed the highest ability to secrete IL-10 while Mo had the highest ability to secrete IL-6. (2)After trauma hemorrhage, the secretion of IL-6 and IL-10 by AM were increased dramatically. On the contrary, the secretion of IL-6 by PM was declined from the 1st day to the 4th day, then increased even over that of the normal control group on the 7th day. However, the secretion of IL-10 by PM was significantly elevated on the 1st day after trauma hemorrhage, peaking on the 4th day, and only slight lowering was found on the 7th day. The secretion of IL-6 by Mo was declined gradually all the time, reaching the lowest point on the 7th day. On the contrary, the secretion of IL-10 by Mo was increasing, reaching its peak on the 7th day. CONCLUSION: The heterogeneity of secretion ability of Mo/macrophage obtained from different anatomical regions is present under normal condition, and is more obvious following a severe injury. This change may play an important role in the immune dysfunction and the development of complications after trauma.

[Application of proteomic technology in the study on infection].

Proteomics is aimed to illuminate the expression and function pattern of global protein in given organism, tissue, cell or subcellular structure. And its technical platform consists of high throughout protein separation and identification technology combined with bioinformatic technology. In many research fields, proteomic technology provided comprehensive, dynamic, and reticular proteome information critical for the understanding of the molecular mechanism of disease processes or life phenomena. As infection is one of the most basic etiological factors, the strategy and technology of proteomics would be very useful in isolation and identification of pathogen proteome, host immune cellular proteome, infection-related proteins, vaccine candidate antigens, biomarkers and drug target proteins, which would then obviously promote the processes of infection-related research, such as pathogen, host response, mechanism of infection as well as the prophylaxis, diagnosis, and therapy of infection.

A regulatory loop involving miR-29c and Sp1 elevates the TGF-ß1 mediated epithelial-to-mesenchymal transition in lung cancer.

Specificity protein1 (Sp1) is required for TGF-ß-induced epithelial-to-mesenchymal transition (EMT) which has been demonstrated to aggravate the progression of cancer including lung cancer. microRNA-29c (miR-29c) is identified to inhibit EMT, but the correlation between miR-29c and Sp1 in human lung cancer remain incompletely clarified. Here, we confirmed decreased expression of miR-29c and enhanced expression of Sp1 in lung cancer tissues (n = 20) and found that Sp1 could be targeted and inhibited by miR-29c. Besides, the expression of miR-29c was down-regulated in high-metastatic lung cancer cell lines and TGF-ß1-treated cells. The inhibition of miR-29c or overexpression of Sp1 in 95C and A549 cells dramatically enhanced the cell migration and invasion, and also induced the decrease in the expression of epithelial markers, e.g. thyroid transcription factor 1 (TTF-1) and E-cadherin, together with an increase in mesenchymal markers including vimentin, α-smooth muscle actin (α-SMA), which could be restored by overexpression of miR-29c mimics during the TGF-ß-induced EMT. Moreover, dual-luciferase reporter assay was performed and the results indicated that miR-29c/Sp1 could form an auto-regulatory loop with TGF-ß1, which impaired TGFB1 transcription. Furthermore, miR-29c overexpression could abrogate the tumor progression and inhibit the Sp1/TGF-ß expressions in vivo, indicating that miR-29c could be a tumor suppressor and repress the Sp1/TGF-ß axis-induced EMT in lung cancer.

[The role of myeloid differential protein-2 in innate immunity].

As typical PRRs (pattern-recognition receptors), TLRs (Toll-like receptors) play an important role during innate immunity recognition. MD-2 (myeloid differential protein-2) may contain distinct functional domains that can separately and simultaneously bind TLRs (TLR4 or TLR2) and TLR ligands, such as lipopolysaccharide (LPS). The special structure of MD-2 may result in its three main functions: (1) An association with TLR4 that amplifies TLR4 responsiveness to ligands, especially LPS. (2) Enabling TLR2-mediated responses to LPS and enhancing TLR2-mediated responses to bacteria and their cell wall components. (3) Increasing the expression of TLR2 and TLR4 and possibly influencing the correct intracellular distribution of TLR4. Importantly, while MD-2 regulation of TLR expression and distribution is well established, determining whether the interaction is direct or not will require further study. Thus, MD-2 is not only an assistant molecule of TLR4 but is also a key regulatory molecule in innate immunity, and may play important roles during infection, inflammation, immune responses and many other pathologic and physiologic processes.

[The use of gene expression differential display analysis technics in trauma research].

Gene is the regulation core of cell proliferation, differentiation and maturation. It is also the decisive factor of occurrence, progression and prognosis of many diseases. The changes in gene expression will inevitably lead to many kinds of abnormal in cells, tissue, organs even in whole biological organism. Trauma, as well as other stimulators, may bring a series complications through the abnormal expression of genes following injury. With the development of bioinformatics and molecular biology, a series of assays (so called gene expression differential display analysis technics, such as DNA microarray) have been established, which have been used to analyze differentially expressed genes effectively. These methods have been widely used in the research of tumor and other disease. This review will focus to some usage of the ways in traumatology.

[Effect of endotoxin pretreatment-induced glycogen synthase kinase-3 inhibition on glycogen metabolism in rat liver and the mechanism].

OBJECTIVE: To investigate the changes in the functional activity of glycogen synthase kinase-3 (GSK-3) in the hepatic tissue after endotoxin (lipopolysaccharide, LPS) tolerance and explore the effects of LPS-induced GSK-3 inhibition on glycogen metabolism in the liver. METHODS: Male SD rats were randomly divided into normal control, endotoxin pretreatment and GSK-3 inhibitor (lithium chloride) groups with corresponding pretreatments prior to a large dose of LPS challenge (10 mg/kg) to induce liver injury. Glycogen deposition and content in the hepatic tissue was detected using periodic acid-Schiff (PAS) staining and a glycogen quantification kit, respectively. Western blotting was performed for semi-quantitative analysis of protein level and inhibitory phosphorylation of GSK-3, and a Coomassie brilliant blue G-250-based colorimetric assay was used to detect calpain activity in the liver. RESULTS: Glycogen content in the liver decreased significantly after LPS challenge in all the 3 groups (P<0.05) but showed no significant difference among the groups (P>0.05). Both LPS and lithium chloride pretreatments caused a significant increase of liver glycogen content (P<0.05). LPS pretreatment induced inhibitory phosphorylation of GSK-3ß (P<0.05) and partial cleavage of GSK-3α but did not affect the expression of GSK-3 protein (P>0.05). Large-dose LPS challenge significantly increased the activity of calpain in the liver tissue (P<0.05) to a comparable level in the 3 groups (P>0.05). CONCLUSION: Endotoxin pretreatment induces inhibitory phosphorylation of GSK-3ß and partial cleavage of GSK-3α and promotes the deposition of liver glycogen but does not affect the activity of calpain, which may contribute to an increased glycogen reserve for energy supply in the event of large-dose LPS challenge.

Identification of synthetic peptides that inhibit lipopolysaccharide (LPS) binding to myeloid differentiation protein-2 (MD-2).

Many studies have suggested that the synergic effect of myeloid differential protein-2 (MD-2) on bacterial lipopolysaccharide (LPS) stimulation of toll-like receptor 4 (TLR4) may be a critical step during the LPS-TLR4 response signaling pathway. We performed a bioinformatic analysis on the MD-2 protein and identified the amino acid sequence NH2-FSKGKYKCV-COOH (K128-132) as a possible key sequence involved in the binding between MD-2 and LPS. We then screened a random phage display peptide library using this sequence as bait in order to identify antagonistic peptides. After 3 rounds of selection, 3 positive clones were identified. All 3 peptides were shown to inhibit, in a dose-dependent manner the production of tumor necrosis factor-α and interleukin-6 in human U937 and THP-1 cell lines as well as human peripheral blood monocytes stimulated by LPS. Only 2 of the 3 peptides were able to bind MD-2 directly as shown by sulfo-SBED biotin label transfer experiments. BALB/C mice were used to estimate the protection of these peptides from LPS challenge, and 2 of the 3 peptides (Lys-Thr-Val-Pro-Asp-Asn-His and Ile-Gly-Lys-Phe-Leu-Tyr-Arg) reduced mortality of the challenged mice from 100% to 53.8%. This study has demonstrated that interfering with the binding between MD-2 and LPS might be a potential therapeutic strategy for treating LPS-induced sepsis, and in doing so has identified 2 potential peptide candidates.

Triggering receptor in myeloid cells (TREM-1) specific expression in peripheral blood mononuclear cells of sepsis patients with acute cholangitis.

To determine its relationship with acute cholangitis (AC), we sought to quantify expression of triggering receptor expressed on myeloid cells (TREM-1) in peripheral blood mononuclear cells (PBMC) of sepsis patients with AC. Peripheral blood samples of 42 AC patients and 48 patients with AC of severe type (ACST) were collected from January to September, 2008 and tested for TREM-1 mRNA by RT-PCR and protein expression by immunocytochemistry and Western blotting. ELISA and immunoturbidimetry were employed to detect the changes of TNF-alpha or C-reactive protein in the serum respectively. TREM-1 expression was higher in ACST group than in AC group (P < 0.01). TREM-1 was positive in mononuclear cells by immunochemistry in both groups before operative therapy, but the positive expression rate decreased at 48 h postoperatively. Compared with healthy controls, TREM-1 protein expression levels were up-regulated in sepsis patients with AC. TREM-1 expression has highly sensitivity and specificity in sepsis patients with AC or ACST. TREM-1 is up-regulated in PBMC of AC patients, and has higher sensitivity and specificity than other clinical inflammation markers, suggesting its importance in AC-induced sepsis.

[Expression of human triggering receptor expressed on myeloid cells 1 in peripheral blood mononuclear cells of patients with acute obstructive suppurative cholangitis].

OBJECTIVE: To investigate the expression pattern of human triggering receptor expressed on myeloid cells 1 (TREM-1) mRNA in peripheral blood mononuclear cells and its clinical significance in acute obstructive suppurative cholangitis (AOSC). METHODS: Peripheral blood mononuclear cells were collected from 36 patients with AOSC and 40 healthy adults. TREM-1 mRNA was determined by semi-quantitative RT-PCR, and TREM-1 protein by immunocytochemistry. Enzyme-linked immunosorbent assay (TNF-alpha) was used to detect the level of tumor necrosis factor-alpha (TNF-alpha), and immunoturbidimetry employed to detect C reactive protein. RESULTS: The expression of TREM-1 mRNA relative to beta-actin was 1.007-/+0.252 in patients with AOSC, significantly higher than that in the healthy adults (0.457-/+0.053, P<0.05). The two groups also showed significantly different TREM protein expression (P<0.01). The AOSC patients exhibited significantly higher levels of TNF-alpha and C reactive protein than the healthy adults (P<0.01). CONCLUSION: The expression of human TREM-1 in peripheral blood mononuclear cells is up-regulated obviously in early stage of AOSC, probably suggesting an important role of TREM-1 in the development of AOSC.

A discovery of low hydraulic resistance channel along meridians.

A hydro-mechanic model was put forward to study the fundamental nature of acupuncture meridians. The basic state of low hydraulic resistance was tested on humans and mini pigs using three methods. The first, a modified Guyton's method, proved that there was lower hydraulic resistance on meridians compared with nonmeridians. The second scanning method involved a single pressure transducer that can find the lowest resistance point in tissue, and the third method used two transducers and provided a more stable measurement. Using the latter method, low hydraulic resistance points were found very close to low impedance points along meridians. The transmission of artificial interstitial fluid pressure waves was measured to examine their connection to the low resistance points, with the result that a good connection between the points was confirmed. This means the points form channels along the meridians that we refer to as low hydraulic resistance channels. The channel was imaged through isotopic tracing and a migration of isotope (99m)Te could be found along the channel. The layer of the channel was detected by injecting Alcian blue and the track was found beneath the skin. All of the above experiments suggest the existence of a new type of channel in living tissues that has not yet been described in modern science, but coincides quite well with the Qi channel theory of traditional Chinese medicine.