[Research on ontology construction of acupuncture effect based on ISO/TS 16843-6: 2022].

In order to specify the information expression of acupuncture effect and realize the knowledge reuse and sharing, in view of animal experiments and clinical trials, the relevant knowledge of acupuncture effect is allocated. Using seven-step method and Protégé5.5.0 tool, the ontology of acupuncture effect is constructed on the base of ISO/TS 16843-6: 2022. A total of 199 classes are constructed, including 7 categories (acupuncture point, acupuncture therapy, needling method, biological process, genes and gene products, disorder, and anatomic structure), 12 object properties, 1 108 instances and 5 123 axioms. A semantic network with the characteristics of acupuncture and moxibustion is established and the structured expression for the knowledge of acupuncture effects is obtained, which lays the foundation for the innovation and development in the field of acupuncture and moxibustion.

Evaluation Model for Hospital Response Capability for Public Health Emergency.

OBJECTIVES: We aimed to explore and create an evaluation model to assess hospital response capability for a public health emergency (PHE). METHODS: Grounded theory was used to construct a comprehensive evaluation index system. Combining with the index system and previous studies and policy documents, we investigated surge capability of hospitals in a PHE. The factor analysis method was used to establish the model. RESULTS: The comprehensive evaluation system with 11 primary and 30 secondary indicators was constructed. A total of 89 secondary and tertiary hospitals were surveyed in China. The evaluation model (C = 0.587C1 + 0.151C2 + 0.140C3 + 0.122C4) was established. Four factors were identified, namely, preparation factor, treatment factor, emergency awareness factor, and prehospital first-aid factor. CONCLUSIONS: A public health emergency could bring huge losses and a capable hospital response was necessary. There was an urgent need to evaluate hospital capability for a PHE.

PuMYB21/PuMYB54 coordinate to activate PuPLDß1 transcription during peel browning of cold-stored "Nanguo" pears.

Refrigeration is commonly used to extend the storage life of "Nanguo" pears, but fruit in long-term refrigeration is prone to peel browning, which is related to membrane lipid degradation. To determine the mechanism of membrane lipid degradation, we identified two R2R3-MYB transcription factors (TFs), PuMYB21 and PuMYB54, from "Nanguo" pears, which were notably expressed in response to cold stress and during the peel-browning process. The results from yeast one-hybrid, electrophoretic mobility shift, and transient expression assays indicated that both PuMYB21 and PuMYB54 directly bind to the promoter of PuPLDß1 (a key enzyme catalyzing the hydrolysis of membrane phospholipids) and activate its expression, which probably enhances the degradation of membrane phospholipids and eventually results in peel browning. Moreover, the overexpression of PuMYB21 and PuMYB54 can greatly activate the transcription of endogenous PuPLDß1 in both "Nanguo" pear fruits and calli, and their silencing can inhibit its transcription. Furthermore, yeast two-hybrid, bimolecular fluorescence complementation, and pull-down assays verified that PuMYB21 interacts with PuMYB54 to enhance the expression of PuPLDß1. In summary, we demonstrate that PuMYB21 and PuMYB54 may have roles in membrane lipid metabolism by directly binding to the downstream structural gene PuPLDß1 during the low temperature-induced peel browning of "Nanguo" pears.

Transcriptome analysis of harvested bell peppers (Capsicum annuum L.) in response to cold stress.

Bell peppers are valued for their plentiful vitamin C and nutritional content. Pepper fruits are susceptible to cold storage, which leads to chilling injury (CI); however, the crucial metabolic product and molecular basis response to cold stress have not been elucidated definitely yet. To comprehensively understand the gene regulation network and CI mechanisms in response to cold stress on a molecular level, we performed high-throughput RNA-Seq analysis to investigate genome-wide expression profiles in bell peppers at different storage temperatures (4 °C and 10 °C). A total of 61.55 Gb of clean data were produced; 3863 differentially expressed genes (DEGs) including 1669 up-regulated and 2194 down-regulated were annotated and classified between the CI group and control. Together, a total of 41 cold-induced transcription factor families comprising 250 transcription factors (TFs) were identified. Notably, numerous DEGs involved in biomembrane stability, dehydration and osmoregulation, and plant hormone signal transduction processes were discovered. The transcriptional level of 20 DEGs was verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Our results present transcriptome profiles of bell peppers in response to cold stress; the data obtained may be useful for the identification of key candidate genes and elucidation of the mechanisms underlying membrane damage during chilling injury.

Reprogramming factors induce proliferation and inhibit apoptosis of melanoma cells by changing the expression of particular genes.

Uncontrolled proliferation and defective apoptosis are two major factors responsible for maintaining the malignant properties of melanoma cells. Our previous study demonstrated that induced expression of four reprogramming factors remodeled the phenotype of B16­F10 mouse melanoma cells into melanoma stem cells. The present study was conducted to investigate the effect of the four Yamanaka reprogramming factors, namely Oct4, Sox2, Klf4 and c­Myc (OSKM), on the proliferation and apoptosis of melanoma cells, and to identify the responsible molecular signals. The results identified that expression of the four reprogramming factors was highly induced by doxycycline treatment in the stable melanoma cell clone that was transfected with a plasmid expressing these factors, driven by the Tet­On element. It was further confirmed that induced expression of these factors enhanced the proliferation and suppressed the apoptosis of the melanoma cells. In addition, induced OSKM expression increased cell proliferation, accelerated the progression of the cell cycle, and upregulated the mRNA expression levels of Janus kinase 2 (JAK2) and Cyclin­B1. Induced expression of these factors also decreased the apoptosis, as well as upregulated B­cell lymphoma 2 (BCL­2) and downregulated BCL­2­associated X (BAX) mRNA expression levels. Taken together, the results suggested that upregulated JAK2 and Cyclin­B1 may be responsible for the enhanced proliferation of melanoma cells, and that BCL­2 upregulation and BAX downregulation may account for the suppressed apoptosis of these cells.

Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations.

The main goal of our study was to characterize the population pharmacokinetics of vancomycin in critically ill Chinese neonates to develop a pharmacokinetic model and investigate factors that have significant influences on the pharmacokinetics of vancomycin in this population. The study population consisted of 80 neonates in the neonatal intensive care unit (ICU) from which 165 trough and peak concentrations of vancomycin were obtained. Nonlinear mixed effect modeling was used to develop a population pharmacokinetic model for vancomycin. The stability and predictive ability of the final model were evaluated based on diagnostic plots, normalized prediction distribution errors and the bootstrap method. Serum creatinine (Scr) and body weight were significant covariates on the clearance of vancomycin. The average clearance was 0.309 L/h for a neonate with Scr of 23.3 µmol/L and body weight of 2.9 kg. No obvious ethnic differences in the clearance of vancomycin were found relative to the earlier studies of Caucasian neonates. Moreover, the established model indicated that in patients with a greater renal clearance status, especially Scr < 15 µmol/L, current guideline recommendations would likely not achieve therapeutic area under the concentration-time curve over 24 h/minimum inhibitory concentration (AUC24h/MIC) ≥ 400. The exceptions to this are British National Formulary (2016-2017), Blue Book (2016) and Neofax (2017). Recommended dose regimens for neonates with different Scr levels and postmenstrual ages were estimated based on Monte Carlo simulations and the established model. These findings will be valuable for developing individualized dosage regimens in the neonatal ICU setting.

Realization of Functional Complete Stateful Boolean Logic in Memristive Crossbar.

Nonvolatile stateful logic computing in memristors is a promising paradigm with which to realize the unity of information storage and processing in the same physical location that has shown great feasibility for breaking the von Neumann bottleneck in traditional computing architecture. How to reduce the computational complexity of memristor-based logic functions is a matter of concern. Here, based on a general logic expression, we proposed a method to implement the arbitrary logic of complete 16 Boolean logic in two steps with one memristor in the crossbar architecture. A representative functional complete NAND logic is successfully experimentally demonstrated in the filamentary Ag-AgGeTe-Ta memristors to prove the validity of our method. We believe our work may promote the development of the revolutionary logic in memory architectures.

S-benzyl-cysteine-mediated cell cycle arrest and apoptosis involving activation of mitochondrial-dependent caspase cascade through the p53 pathway in human gastric cancer SGC-7901 cells.

S-benzyl-cysteine (SBC) is a structural analog of S-allylcysteine (SAC), which is one of the major water- soluble compounds in aged garlic extract. In this study, anticancer activities and the underlying mechanisms of SBC action were investigated and compared these with those of SAC using human gastric cancer SGC-7901 cells. SBC significantly suppressed the survival rate of SGC-7901 cells in a concentration- and time-dependent manner, and the inhibitory activities of SBC were stronger than those of SAC. Flow cytometry revealed that SBC induced G2-phase arrest and apoptosis in SGC-7901 cells. Typical apoptotic morphological changes were observed by Hoechst 33258 dye assay. SBC-treatment dramatically induced the dissipation of mitochondrial membrane potential (Δψm), and enhanced the enzymatic activities of caspase-9 and caspase-3 whilst hardly affecting caspase-8 activity. Furthermore, Western blotting indicated that SBC-induced apoptosis was accompanied by up-regulation of the expression of p53, Bax and the down-regulation of Bcl-2. Taken together, this study suggested that SBC exerts cytotoxic activity involving activation of mitochondrial-dependent apoptosis through p53 and Bax/Bcl-2 pathways in human gastric cancer SGC-7901 cells.

Macrophages and T lymphocytes are the predominant cells in intimal arteritis of resected renal allografts undergoing acute rejection.

BACKGROUND: In acute renal allograft rejection, T-cell-mediated processes have been generally regarded as dominant. Although there is recent evidence that macrophages play important roles in acute vascular rejection, less is known about the exact proportion of immunocytes in the intimal arteritis of renal allografts with unfavorable outcomes. METHODS: By immunohistochemical staining using nine primary antibodies, we classified the proportions of infiltrating immunocytes in intimal arteritis and glomerulitis in five allografts resected because of acute irreversible graft failure. RESULTS: All five allografts had features of antibody-mediated rejection based on criteria established by the Banff classification. In intimal arteritis, CD3+ T-lymphocytes accounted for 30.6±13.3% of the immunocytes and macrophages for 40.4±9.2%. 45.4% of the T-cells were CD8+ cytotoxic T-cells. Neutrophils were also present but accounted for a relatively low proportion of the cells (8.8±8.6%). B-cells and plasma cells all accounted for <5% of the immunocytes. NK cells were readily detected (4.2±4.2%). When we compared types of arteritis, the CD15+ neutrophils accounted for as many as 27.8±15.1% of immunocytes in V3 vasculitis and only 1.0±1.4% in V2 vasculitis. CD3+ T-lymphocytes accounted for 25.8±7.3% of immunocytes in V3 vasculitis and 41.5±7.9% in V2 vasculitis. In glomerulitis, the immunocytes were mainly macrophages (53.1±9.1%) and neutrophils (34.6±9.9%). CONCLUSION: Macrophages and T-lymphocytes accounted for the highest percentage of immunocytes in the intimal arteritis of irreversible renal failure associated with antibody-mediated rejection. 45.4% of the T-cells were CD8+ cytotoxic T-cells. Neutrophils and NK cells were also present in these lesions. The proportion of neutrophils in V3 vasculitis was much higher than in V2 vasculitis. These observations suggest that besides macrophages and T-lymphocytes, neutrophils may also play a role in the more severe arterial lesion. To our knowledge this is the first report of this observation. Macrophages and neutrophils were the main inflammatory cells in the glomerulitis of acute rejection.

Effect of matrine on the expression of substance P receptor and inflammatory cytokines production in human skin keratinocytes and fibroblasts.

Matrine is a kind of alkaloid found in certain Sophora plants, which has been extensively used in China for the treatment of viral hepatitis, cancer, cardiac diseases and skin diseases (such as atopic dermatitis and eczema). It also has been confirmed that substance P (SP) and its receptor (neurokinin-1 receptor, NK-1R) are involved in the pathogenesis of inflammatory skin disorders. So the present study was designed to investigate the effect of matrine on the expression of NK-1R and cytokines production induced by SP in HaCaT cells (a human epidermal keratinocyte cell line) and dermal fibroblasts. In addition, cell viability was also evaluated. The results showed that matrine inhibited the expression of NK-1R in HaCaT cells and fibroblasts. SP induced the production of interleukin (IL)-1beta, IL-8, interferon (IFN)-gamma, and monocyte chemotactic protein (MCP)-1 in both cell types. Matrine 5-100 microg/mL had little effect on cell viability. It inhibited SP-induced IL-1beta, IL-8 and MCP-1 production in HaCaT cells and fibroblasts, while it increased the production of IFN-gamma in HaCaT cells. Both SP and matrine had no effect on the secretion of IL-6. These findings suggest that matrine may have potential treatment function on SP related cutaneous inflammation by inhibition of the expression of substance P receptor and regulation of the production of inflammatory cytokines.

[Effect of cetirizine hydrochloride on the expression of substance P in IgE-mediated triphasic cutaneous reaction].

AIM: To investigate the effect of cetirizine hydrochloride on the expression of neuropeptide substance P (SP) in IgE-dependent triphasic cutaneous reaction induced by dinitrofluorobenzene (DNFB) in the ears of BALB/c mice. METHODS: BALB/c mice were passively sensitized by intravenous infection of anti-DNP IgE monoclonal antibody 24 h before DNFB challenge. Skin reaction was elicited by applying DNFB to both sides of each ear of sensitized mice. Mice were treated with cetirizine (1 and 10 mg x kg)-1), ig). The ears were removed for pathohistological examination and immunohistochemical staining of SP at different designated times after challenge. The contents of SP in the skin of mouse ear were determined by radioimmunoassay (RIA). RESULTS: The mice exhibited a triphasic cutaneous reaction with an immediate-phase response (IPR) at 1 h, a late-phase response (LPR) at 24 h and a very late-phase response (vLPR) at 7 days after challenge with DNFB. The expression of SP in different phases increased gradually. Cetirizine (1 and 10 mg x kg(-1)) was shown to significantly inhibit the ear swellings induced by the IPR (P < 0.01), while no obvious effect on the vLPR. The SP contents in ear skin of triphasic cutaneous reaction were decreased by cetirizine. CONCLUSION: SP is considered to be involved in the pathogenesis of allergic dermatitis. Cetirizine hydrochloride can inhibit the expression of SP in IgE-dependent triphasic cutaneous reaction. It might be part of the mechanisms of anti-anaphylaxis of cetirizine.

[Relativities between lattice changes and the function of dissolution improvement of poorly soluble drug silymarin based upon PEG 6,000 solid dispersion system].

AIM: To investigate the lattice mechanisms involved in the increased dissolution effect of polyethylene glycol (PEG 6,000) dispersion system on poorly soluble drug silymarin (SILY). METHODS: Fusion method was used to prepare the solid dispersions of SILY with PEG 6,000. Evaluation of the improvement of dissolution was performed with dissolution studies in vitro. X-ray powder diffraction combined with diffraction peak pattern-fitting procedure were applied to quantitatively analyze the changes of lattice parameters. The interaction of SILY and PEG 6,000 was also determined with Fourier transform-infrared (FT-IR) spectroscopy. RESULTS: The dissolution rate of SILY was considerably increased when formulated in solid dispersion of PEG 6,000 as compared to pure SILY. The datum from the X-ray diffraction showed the changes in the lattic spacings and particular diffraction peaks (position and the intensity) of PEG 6,000 and SILY. These could explain the increased rate of SILY released from solid dispersion system. The information of FT-IR spectroscopy showed the absence of well-defined drug-polymer interaction. CONCLUSION: The dissolution improvement of poorly soluble SILY from solid dispersion of PEG 6,000 can be illuminated by the changes of the lattice parameters of PEG 6,000 and the drug.