Oxidative stress could destroy the structures and functions of many biological molecules (such as nucleic acids,proteins,lipids) and undermine many physiological activities,such as gene expression regulation,cell signal transduction,substance uptake and intracellular transport,thus leading to many tissue and organ pathological damages. Carnosic acid,rich in rosemary (Rosmarinus officinalis L.),could retard or prevent oxidative stress by activating the cellular antioxidant system (such as Nrf2-Keap1,Sirt1 signaling pathway) or inhibiting pro-oxidant signaling pathways (such as NF-κB,AGEs,etc.) to scavenge reactive oxygen species. It exhibits favorable effects on the prevention and treatment of oxidative stress-related diseases involving nervous system,retina,cardiovascular,liver,etc. The modulation mechanisms of carnosic acid on these diseases are summarized in this review,which shall provide a reference for promoting the clinical applications of carnosic acid.

Long-term consumption of olive oil helps reduce the risks of developing a series of diseases including cardiovascular disease, nervous system disease, cancer, etc. The minor compounds of olive oil, especially the star molecule--hydroxytyrosol, play an important role in these beneficial effects on human health. As a polyphenolic compound, hydroxytyrosol not only act as antioxidant and scavenge oxidizing substances directly, but also inhibit oxidative stress by regulating the Nrf2 antioxidant system. Thus, hydroxytyrosol has great potential in the prevention and treatment of oxidative damage related diseases. This review focuses mainly on recent progresses in pharmacological effects of hydroxytyrosol on nervous system disease, angiocardiopathy, metabolic syndrome, inflammation and cancer.

Objective To observe the effect of Chinese medicine Tangshenling, which can increase function of spleen and kidney and, remove blood stasis, on early Diabetic Nephropathy, and explore the mechanism. Methods 70 cases of early diabetic nephropathy were observed for comparation with 2 months as a course of treatment. The observing indexes were clinical symptoms, blood fat, blood sugar, HbA1C, UAER, Urine ?2-MG. Results Tangshenling could evidently not only improve the symptoms of early DN patients but also decrease blood fat, blood sugar, UAER, HbA1C and Urine ?2-MG. Conclusion Tangshenling could improve the high blood sugar, high blood fat of the early DN patients, decrease UAER, protect kidney function, which proves Tangshenling has definite curative effect on early DN.

Silent mating type information regulator 2-related enzymes or sirtuin family proteins are nicotinamide adenine dinucleotide (NAD

BACKGROUND: Digit amputation coupled with neighboring composite skin loss frequently occurs. Conventional treatment for this lesion is somewhat less desirable in that it either results in shortened or lost fingers as well as delayed skin resurfacing. Therefore, the curative effect is not satisfactory.OBJECTIVE: To observe free forearm venous flap for soft-tissue reconstruction in digit amputation accompanied with neighboring soft tissue loss and postoperative rehabilitation and its effect on functional recovery.DESIGN: Before-and-after controlled observational trial based on the patients.SETTING: Department of orthopedics of a university hospital.PARTICIPANTS: Totally 11 patients, 8 males and 3 females aged 20 to 45years, who were treated between October 2000 and May 2004 in the Department of Orthopedics, Third Affiliated Hospital of Sun Yat-sen University,for digit amputations accompanied with composite skin flaps avulsed in dorsal fingers or hand, were recruited.METHODS: Eleven free venous flaps measuring 1. 5 cm × 1.0 cm to 5 cm × 6. 5 cm from anteromedial ipsilateral forearms were elevated and transferred to the defected sites either antegradely or retrogradely with respect to the nature of the defects. Microvascular anastomosis was performed at both ends of the flaps to the wounds in an end-to-end fashion. Digit replantations in 13 digits were performed simultaneously at one stage. The donor sites were closed primarily by direct suturing or skin grafting. After operation, early rehabilitation was initiated under professional guidance.RESULTS: Complete healing was achieved in 9 out of 11 venous flaps and 12 out of 13 replanted digits. After one-year follow-up, finger motion function in seven cases was satisfactory; however, all the flaps presented diminished sensation.CONCLUSION: The free venous flap from anteromedial forearm is an alternative flap for soft-tissue reconstruction in digit amputation. Easy access,ideal thickness, and good pliability are the advantages of the flap whereas limited sensory recovery is the main shortcoming.

Due to their high catalytic activity and substrate specificity, enzymes have broad applications in commodity chemistry, medicine, food manufacturing, pollution prevention and control, etc. However, their actual applications are compromised by disadvantages such as difficulty to separate and purify, high cost and poor stability. It is of great significance to explore artificial substitutes for enzymes. Ferroferric oxide nanoparticles were reported to have peroxidase-like activity by Dr. Xiyun Yan for the first time in 2007. Since then the researches about nanomaterials with catalytic activities have emerged in large numbers. In addition to peroxidase-like activities, nanomaterials also possessed many enzyme-like catalytic activities such as oxidase, superoxide dismutase and catalase. Nanomaterials with enzyme-like activities are usually referred as nanozymes. As an alternative to natural enzymes, nanozymes possess characteristics such as low costs, easy mass production, high stability and adjustable activity. Those nanozyme characteristics have broad applications in environmental monitoring and management, disease diagnosis and treatment, food safety control, etc. However, low catalytic efficiency and specificity limit further applications of nanozymes. Therefore, enhancing the catalytic activities and selectivity of nanozymes will promote their applications. The catalytic activity of nanozymes can be regulated by changes in nanomaterials (size, morphology and surface modification) and catalytic reaction conditions (temperature, pH, accelerators, light irradiation, etc.), mixing of different nanomaterials, nanomaterial hybridization, and so on. The most widely used catalytic activity of nanozymes is peroxidase-like activity. This review summarizes the strategies to enhance peroxidase-like activities of nanomaterials, mainly focuses on catalytic efficiency and substrate specificity. It is expected that readers can have a comprehensive understanding of the strategies to enhance the enzyme-like activity of nanomaterials.

Objective: To investigate the effect and related mechanism of homocysteine (Hcy) on calcium overload in neonatal rat atrial cells (NRICs). Methods: NRICs were assigned to 9 groups after culture for 3 days: (1) control group; (2) Hcy group (0, 50, 100, 200, 500 μmol/L for 48 hours); (3) antioxidant group (NAC, 10 μmol/L for 24 hours); (4) Hcy+NAC group (500 μmol/L Hcy for 48 hours, then treated with 10 μmol/L NAC for 24 hours); (5) calcium/calmodulin dependent protein kinase Ⅱδ (CaMKⅡδ) inhibitor group (KN-93, 3 μmol/L KN-93 for 5 hours); (6) specific sodium current inhibitor group (ELE, 1 μmol/L ELE for 5 hours); (7) Hcy+KN-93 group (500 μmol/L Hcy for 48 hours, then treated with 3 μmol/L KN-93 for 5 hours); (8) Hcy+ELE group (500 μmol/L Hcy for 48 hours, then treated with 1 μmol/L ELE for 5 hours; (9) Hcy+KN-93+ELE group (500 μmol/L Hcy for 48 hours, then treated with 3 μmol/L KN-93 and 1 μmol/L ELE for 5 hours). Moreover, NRICs were also treated with CaMKⅡδ-siRNA lentivirus, and Nav1.5-siRNA lentivirus, negative lentivirus carrier containing green fluorescent protein (GFP) for 24 hours. The MOI values of the three groups were 10. Infection efficiency of lentivirus was determined by observing the percentage of GFP fluorescence under inverted fluorescence microscope after transfection for 24 hours, and cultured regularly with simultaneous Puro screening, then cells were grouped as Hcy+CaMKⅡδ-siRNA group, Hcy+Nav1.5-siRNA group and Hcy+negative group. The concentration of Ca²⁺ in NRICs ([Ca²⁺]i) of various groups was detected through Fluo-4/AM fluorescence probe, then 2', 7'- two chlorofluorescein diacetate (DCFH-DA) was used as a probe to detect reactive oxygen species (ROS) in NRICs by flow cytometry. The malondialdehyde (MDA) was detected by the activity of superoxide dismutase (SOD) and xanthine oxidase was detected by thiobarbituric acid colorimetry. The protein and mRNA expression level of CaMKⅡδ and Nav1.5 in NRICs were detected by Western blot and quantitative real-time PCR. Results: (1) ROS, MDA and SOD were similar between NAC group and control group, ROS and MDA were significantly increased, while SOD was significantly reduced in Hcy group in a concentration-dependent manner. (2) [Ca²⁺]i: The level of [Ca²⁺]i was (155.57+7.25), (187.43+13.07), (248.98+27.22) and (307.36+15.09) nmol/L in 50, 100, 200 and 500 μmol/L Hcy groups, which was significantly higher than that in the control group ((123.18+7.24) nmol/L, P<0.01). In addition, the level of [Ca²⁺]i in Hcy+NAC group ((222.87+23.71)nmol/L) was significantly lower than that in Hcy 500 μmol/L group ((305.15+39.45) nmol/L, P<0.05), while [Ca²⁺]i level was similar between NAC group and the control group. (3) The protein expression of CaMKⅡδ and Nav1.5 was significantly upregulated in Hcy groups than in the control group. The protein expression level of CaMKⅡδ-Thr287 was significantly lower in NAC group than in Hcy 500 μmol/L group (P<0.01), however, there was no significant difference on the protein expression levels of CaMKⅡδ-Thr287 and Nav1.5 between NAC group and control group (all P>0.05). (4) The protein expression levels of CaMKⅡδ-Thr287 and the concentration of [Ca²⁺]i were significantly lower in Hcy+KN-93 group and Hcy+KN-93+ELE group than in Hcy 500 μmol/L group (P<0.05). [Ca²⁺]i concentration was significantly lower in Hcy+KN-93 group, Hcy+ELE group and KN-93+ELE+Hcy group than in Hcy 500 μmol/L group (P<0.05). (5) The mRNA and protein expression levels of CaMKⅡδ and Nav1.5 in each group infected with lentivirus: the GFP expression was ideal post lentivirus transfection for 24 hours (up to 90%), which was significantly lower in the CaMKⅡδ-siRNA group and Nav1.5-siRNA group than in the negative infection group (all P<0.05), which was similar between negative infection group and control group (P>0.05). Moreover, the mRNA and protein expression levels of CaMKⅡδ and CaMKⅡδ-Thr287 was significantly lower in Hcy+Nav1.5-siRNA group than in Hcy+negative infection group (P<0.05). The protein and mRNA levels of Nav1.5 were similar between Hcy+CaMKⅡδ-siRNA group and Hcy+negative infection group (P>0.05). Conclusions Hcy can induce calcium overload in NRICs by increasing oxidative stress, upregulating the sodium channel protein, and activating the late sodium current and phosphorylating CaMKⅡδ.

The present study explored the mechanism of Fagopyri Dibotryis Rhizoma(FDR) and its main active components in the treatment of acute lung injury(ALI) based on the network pharmacology and the in vitro experiments. The main active components of FDR were obtained from the TCMSP database and screened by oral bioavailability and drug-likeness. The related target proteins of FDR were retrieved from the PubChem database, and the target genes related to ALI were screened out from the GeneCards database. A protein-protein interaction(PPI) network of compound target proteins and ALI target genes was constructed using STRING 11.0. Ingenuity Pathway Analysis(IPA) platform was used to analyze the common pathways of the potential compound target proteins of FDR and ALI target genes, thereby predicting the key targets and potential signaling pathways of FDR for the treatment of ALI. Finally, the potential pathways and key targets were verified by the in vitro experiments of lipopolysaccharide-induced RAW264.7 cells intervened by epicatechin(EC), the active component of FDR. The results of network pharmacology showed that 15 potential active components such as EC, procyanidin B1, and luteolin presumedly functioned in the treatment of ALI through nuclear transcription factor-κB(NF-κB) signaling pathway, transforming growth factor-β(TGF-β) signaling pathway, and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway through key targets, such as RELA(P65). The results of in vitro experiments showed that 25 μmol·L~(-1) EC had no toxicity to cells and could inhibit the expression of the p65-phosphorylated protein in the NF-κB signaling pathway to down-regulate the expression of downstream inflammatory cytokines, including tumor necrosis factor-α(TNF-α), IL-1β and nitric oxide(NO), and up-regulate the expression of IL-10. These results suggested that the therapeutic efficacy of FDR on ALI was achieved by inhibiting the phosphorylation of p65 protein in the NF-κB signaling pathway and down-regulating the level of proinflammatory cytokines downstream of the signaling pathways.
Acute Lung Injury/genetics* ; Lipopolysaccharides ; NF-kappa B/metabolism* ; Rhizome ; Signal Transduction

Objective To investigate the clinical characteristics and risk factors of secondary infection in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).Methods One hundred and eighteen patients newly diagnosed with AAV at the institute of nephrology,Tongji hospital affiliated to Huazhong university of science and technology,from 2012 to 2017,were analyzed retrospectively.Induction therapy included single corticosteroids,combination of corticosteroids with cyclophosphamide and combination of corticosteroids with other immunosuppressive agents.End point was defined as moderate to severe infection which was diagnosed by the clinical and radiological manifestation as well as microbiological evidences.The infection-related survival curve was drawn to reflect the time when the infection occurred.The clinical baseline variables in patients with and without infection were compared.Multivariate Logistic regression model was used to determine the independent predictors of infection.Receiver-operating characteristic curve (ROC) was plotted for evaluating the predictive value of lymphocyte on moderate to severe infection.Results During followup of median 3 months (1-30 months),88 infection episodes were found in 63 (53.4％) patients,of which 54 times (61.4％) occurred within 6 months after treatment,46 times (52.3％) happened within 3 months after treatment.The most common organ of infection was lung (62.5％),and the most common pathogen was bacteria (51.1％).Multivariate Logistic regression model showed that lung involvement (OR=4.44,95％ CI 1.59-12.41),moderate reduction of lymphocyte in follow-up (OR=5.69,95％ CI 2.05-15.85) and severe lymphocyte reduction (OR=36.28,95％CI 3.45-381.17) were independent risk factors of secondary infection in AAV patients (all P ＜ 0.05).ROC curve showed that the area under the curve of lymphocyte as a predictor of severe infection was 0.767 (95％ CI 0.64-0.89,P ＜ 0.05).Based on lymphocyte less than 0.49× 109/L which was the cut-off value for predicting severe infection,the sensitivity and the specificity were 83.9％ and 71.9％,respectively.Conclusions Lung involvement and moderate-severe lymphopenia during follow-up are independent risk factors of secondary infection in AAV patients.Hence,physician should pay more attention to those patients,and adjust treatment in time to avoid the occurrence of infection.

Dry granulation technology is a great innovation in granulation technology,which saves many intermediate links and reduces many intermediate costs. It is closely related to the characteristics of materials,dry granulation equipment and process. Dry granulation technology is a systematic engineering science covering many technical fields. The process of dry granulation involves complex mathematical model mechanisms of temperature field,pressure field and velocity field,closely related to the characteristics of materials and drying equipment. However,due to the late start of research on dry granulation technology of traditional Chinese medicine,basic research is still weak. The research on dry granulation technology has achieved great results in the fields of food,chemical industry,agriculture and forestry,showing great reference significance. The advantage of dry granulation of traditional Chinese medicine is that it can be directly granulated by adding an appropriate amount of auxiliary materials in the extract powder of traditional Chinese medicine,without the need of wetting,mixing,drying and other processes. The process is simple and can effectively guarantee the quality of traditional Chinese medicine. The granules obtained by the dry granulation technique are important intermediates for preparing the solid preparations of traditional Chinese medicines,which would directly affect the subsequent molding process and the quality of the preparation products. Therefore,based on the characteristics of dry granulation method in traditional Chinese medicine and by referring to the advanced research results of dry granulation technology in other fields,we would discuss the research ideas of dry granulation in traditional Chinese medicine in terms of the mechanism of dry granulation equipment,technology,on-line detection technology and mathematical model of dry granulation process,hoping to provide reference for the research of dry granulation method in traditional Chinese medicine.
Desiccation ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Models, Theoretical ; Powders ; Quality Control ; Technology, Pharmaceutical