Design, synthesis and evaluation of antioxidant and anti-inflammatory activities of novel resveratrol derivatives as potential multifunctional drugs.

Oxidative stress and inflammation responses are closely related to the occurrence and development of many diseases. Therefore, anti-oxidation and anti-inflammation have become hot spots in the treatment of diseases. A series of novel resveratrol derivatives which hybrid with benzoylhydrazines were designed, synthesized and assessed for their in vitro antioxidant and anti-inflammatory activity. Initially, the antioxidant abilities of resveratrol derivatives were investigated by DPPH, ABTS radical scavenging and FRAP assays. RAW 264.7 macrophages are routinely used to evaluate the antioxidant and anti-inflammatory activities of drugs, so we used it to construct cell models of oxidative stress and inflammation. Among all the derivatives, compound 5 exhibited superior ROS- and NO-inhibitory activities. The molecular mechanism detected by Western blotting showed that compound 5 could significantly activate the Nrf2 signaling pathway and up-regulate the expression of HO-1 to resist oxidative stress stimulated by H2O2. At the same time, it could down-regulate the expression of apoptosis-related proteins Caspase3 and PARP, alleviating cells damage and apoptosis. In addition, compound 5 dose-dependently inhibited the activation of NF-κB p65/iNOS and MAPKs signaling pathway.

Horizontal semicircular canal benign paroxysmal positional vertigo treated by acupuncture and moxibustion: A case report.

RATIONALE: Horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV) is a second common canal of Benign Paroxysmal Positional Vertigo (BPPV); its actual incidence may have been underestimated because of its complex pathogenesis. Although the canalith repositioning maneuver is the treatment of choice, it has a high recurrence rate, affecting some patients' lives and psychology. We submit a case report describing acupuncture and wheat grain moxibustion treatment for HSC-BPPV. PATIENT CONCERNS: A 70-year-old patient with HSC-BPPV had low acceptability of the otolith repositioning treatment strategy and reported intolerance during the procedure. He turned to acupuncture as a result of recurrent attacks of vertigo. DIAGNOSES: Horizontal semicircular canal benign paroxysmal positional vertigo. INTERVENTIONS: The intervention project was acupuncture followed by wheat grain moxibustion treatment, administered once every 2 days, 3 times a week. The whole treatment period lasted for 2 months. OUTCOMES: The patient's clinical symptoms of vertigo improved significantly after 8 weeks of acupuncture and wheat grain moxibustion treatment. The Dizziness Handicap Inventory (DHI) and Visual Vertigo Analogue Scale (VVAS) scores decreased, thus verifying that the severity of vertigo was reduced. LESSONS: This brief clinical report suggests that acupuncture therapy may be a complementary option for treating HSC-BPPV.

Design, synthesis, biological evaluation and molecular docking study of novel pleuromutilin derivatives containing substituted benzoxazole as antibacterial agents.

A series of pleuromutilin analogs containing substituted benzoxazole were designed, synthesised, and assessed for their antibacterial activity both in vivo and in vitro. The MIC of the synthesised derivatives was initially assessed using the broth dilution method against four strains of Staphylococcus aureus (MRSA ATCC 43300, S. aureus ATCC 29213, clinical isolation of S. aureus AD3 and S. aureus 144). Most of the synthesised derivatives displayed prominent in vitro activity (MIC ≤ 0.5 µg/mL). Compounds 50 and 57 exhibited the most effective antibacterial effect against MRSA (MIC = 0.125 µg/mL). Furthermore, the time-kill curves showed that compounds 50 and 57 had a certain inhibitory effect against MRSA in vitro. The in vivo antibacterial activity of compound 50 was evaluated further using a murine thigh model infected with MRSA (-1.24 log10CFU/mL). Compound 50 exhibited superior antibacterial efficacy to tiamulin. It was also found that compound 50 did not display significant inhibitory effect on the proliferation of RAW 264.7 cells. Molecular docking study revealed that compound 50 can effectively bind to the active site of the 50S ribosome (the binding free energy -7.50 kcal/mol).

Design, synthesis, and biological evaluation of novel pleuromutilin derivatives containing benzimidazoles as effective anti-MRSA agents.

A series of pleuromutilin derivatives containing benzimidazole were designed, synthesized, and evaluated for their antibacterial activities against Methicillin-resistant Staphylococcus aureus (MRSA) in this study. The in vitro antibacterial activities of the synthesized derivatives against four strains of S. aureus (MRSA ATCC 43300, S. aureus ATCC 29213, S. aureus 144, and S. aureus AD3) were determined by the broth dilution method. Among these derivatives, compound 58 exhibited superior in vitro antibacterial effect against MRSA (minimal inhibitory concentration [MIC] = 0.0625 µg/mL) than tiamulin (MIC = 0.5 µg/mL). Compound 58 possessed a faster bactericidal kinetic and a longer post-antibiotic effect time against MRSA than tiamulin. Meanwhile, at 8 µg/mL concentration, compound 58 did not display obviously cytotoxic effect on the RAW 264.7 cells. In addition, compound 58 (-2.04 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (-1.02 log10 CFU/mL) in reducing MRSA load in mice thigh infection model. In molecular docking study, compound 58 can successfully attach to the 50S ribosomal active site (the binding free energy is -8.11 kcal/mol). Therefore, compound 58 was a potential antibacterial candidate for combating MRSA infections.

Population pharmacokinetics and clinical outcomes of polymyxin B in paediatric patients with multidrug-resistant Gram-negative bacterial infections.

BACKGROUND: Current polymyxin B dosing in children relies on scant data. OBJECTIVES: To build a population pharmacokinetic (PK) model for polymyxin B in paediatric patients and assess the likely appropriateness of different dosages. METHODS: A total of 19 paediatric patients were enrolled to receive intravenous polymyxin B (1.33-2.53 mg/kg/day), and the median age was 12.5 (range 3.2-17.8) years. Serial plasma samples were collected at steady-state and modelled by population PK analysis. Clinical efficacy and nephrotoxicity of polymyxin B treatment were also assessed. RESULTS: PK data were adequately described by a two-compartment model with first-order elimination, and weight was a significant covariate of polymyxin B clearance. Clinical success occurred in 14 of 19 patients (73.7%) and only one patient developed acute kidney injury. The 28 day mortality was 10.5% (2/19). The steady-state polymyxin B exposure was 36.97 ±â€Š9.84 mg·h/L, lower than the therapeutic exposure of 50-100 mg·h/L. With the AUC24h/MIC target of 50, the dosage of 1.5-3.0 mg/kg/day had a probability of target attainments over 90% when MICs were <0.5 mg/L. CONCLUSIONS: Dose adjustment of polymyxin B needs to consider the MIC of infecting pathogens. Current polymyxin B dosing for paediatric patients may be acceptable when MICs are <0.5 mg/L.

Design, synthesis, biological evaluation and molecular docking studies of novel pleuromutilin derivatives containing nitrogen heterocycle and alkylamine groups.

A series of pleuromutilin derivatives containing alkylamine and nitrogen heterocycle groups were designed and synthesised under mild conditions. The in vitro antibacterial activity of these semisynthetic derivatives against four strains of Staphylococcus aureus (MRSA ATCC 43300, S.aureus ATCC 29213, S.aureus AD3, and S.aureus 144) were evaluated by the broth dilution method. Compound 13 was found to have excellent antibacterial activity against MRSA (MIC = 0.0625 µg/mL). Furthermore, compound 13 was further studied by the time-killing kinetics and the post-antibiotic effect approach. In the mouse thigh infection model, compound 13 exhibited superior antibacterial efficacy than that of tiamulin. Meanwhile, compound 13 showed a lower inhibitory effect than that of tiamulin on RAW264.7 and 16HBE cells at the concentration of 10 µg/mL. Molecular docking study revealed that compound 13 can effectively bind to the active site of the 50S ribosome (the binding free energy = -9.66 kcal/mol).

[Clinical observation of herb-separated moxibustion on segmental conception vessel combined with low-frequency TEAS for asthenospermia and oligospermia].

OBJECTIVE: To observe the clinical effect of herb-separated moxibustion on segmental conception vessel combined with low-frequency transcutaneous electrical acupoint stimulation (TEAS) for asthenospermia and oligospermia. METHODS: A total of 105 patients with asthenospermia and oligospermia were randomly divided into a combination group, a TEAS group and a medication group, 35 cases in each one. In the medication group, vitamin E capsules, coenzyme Q10 capsules，Wuzi Yanzong pills were taken. In the TEAS group, TEAS was applied at Shenshu (BL 23) and Pishu (BL 20), 2 Hz in frequency, 10-15 mA in intensity, once every 2 days, 30 min each time.On the base of the treatment as the TEAS group, herb-separated moxibustion on segmental conception vessel [Shenque (CV 8) to Zhongji (CV 3)] was applied in the combination group, once every 10 days. A total of 3 months were required in the 3 groups.Before treatment and 2, 3 months into treatment, the semen routine indexes (concentration, normal morphology rate, sperm motility), seminal plasma contents of superoxide dismutase (SOD) and malondialdehyde (MDA) and TCM syndrome score were observed in the 3 groups, and the clinical efficacy was evaluated. RESULTS: Compared before treatment, except for the sperm morphology 2 months into treatment in the medication group, the semen routine indexes 2, 3 months into treatment were improved in the 3 groups (P<0.01), and the semen routine indexes 2, 3 months into treatment in the combination group were superior to the medication group and the TEAS group (P<0.01). Compared before treatment, the seminal plasma contents of SOD were increased and MDA were decreased 2, 3 months into treatment in the 3 groups (P<0.01), and the changes of the combination group were larger than the medication group and the TEAS group (P<0.01). Compared before treatment, the TCM syndrome scores 2, 3 months into treatment in the combination group, and 3 months into treatment in the medication group and the TEAS group were decreased (P<0.01). The TCM syndrome scores 2, 3 months into treatment in the combination group were lower than the medication group and the TEAS group (P<0.01). The total effective rates in the combination group, the medication group and the TEAS group were 85.7% (30/35), 68.6% (24/35) and 65.7% (23/35), the clinical efficacy of the combination group was higher than the medication group and the TEAS group (P<0.05). CONCLUSION: Herb-separated moxibustion on segmental conception vessel combined with low-frequency TEAS can improve semen routine, reduce sperm oxidative stress damage for patients with asthenospermia and oligospermia, and the clinical efficacy is better than the medication and TEAS.

Deciphering the Relationship Between the Trough Concentration of Posaconazole and Its Efficacy and Safety in Chinese Patients With Hematological Disorders.

Posaconazole (PCZ) is effective in preventing and salvage treatment invasive fungal infections in patients with hematologic disorders. However, PCZ displays highly variable individual pharmacokinetics affecting its efficacy and safety. To investigate the correlation between PCZ concentration and efficacy and safety, the following key influencing factors were explored. A total of 285 trough plasma concentrations (Cmin) of 81 Chinese patients receiving PCZ oral suspension for prophylaxis or treatment of invasive fungal infections were collected in this study. The relationships between Cmin values and clinical response and hepatotoxicity were investigated as well as the incidence of clinical response under different Cmin values of PCZ with a logistic regression model. The concentration of PCZ showed remarkable differences among patients with haematologic disorders. PCZ Cmin values of 0.76 and 1.0 µg/mL were both associated with an over 80% probability of successful response to prophylaxis and treatment of fungal infections, respectively. No association between Cmin values and hepatotoxicity was noted (P > 0.05). Gender, albumin, and co-administration of proton pump inhibitor (PPI) were identified as independent factors influencing PCZ Cmin by multiple linear regression analysis. Furthermore, patients' C-reactive protein (CRP), albumin, and co-administration of PPI exhibited significant effects on the therapeutic window of patients receiving PCZ for prophylaxis. The plasma concentration is closely associated with therapeutic efficacy of PCZ. It is necessary to adjust the dosing regimens based on PCZ Cmin to obtain an optimal therapeutic response.

[Exploration of academic ideas on pricking blood therapy of Rumen Shiqin].

Through in-depth excavation and analysis of the pricking blood therapy mentioned in Rumen Shiqin, it is found that ZHANG Zi-he's pricking blood theory is mainly derived from Huangdi Neijing. Innovative development has been carried out on the basis of "brave innovation and careful verification", and at the same time, it has been practiced and summarized clinically to form its own unique pricking blood therapy. This article systematically summarizes formation of the theory, clinical application, characteristics, and influence on later generations of pricking blood therapy in Rumen Shiqin, with a view to inspiring scholars to have a more comprehensive understanding on the pricking blood therapy in Rumen Shiqin, and providing new ideas and reference for clinical application.

Tyrosine hydroxylase is crucial for pupal pigmentation in Zeugodacus tau (Walker) (Diptera: Tephritidae).

Tyrosine hydroxylase (TH) is the initial enzyme responsible for cuticle sclerotization and pigmentation in many insect species, but to date, no direct functional studies have focused on TH in Zeugodacus tau. Here, the 3336-bp full-length cDNA of TH was isolated from Z. tau, a notorious horticultural pest infesting fruits and vegetables. qRT-polymerase chain reaction revealed that ZtTH transcripts were highly abundant at the time of pupal tanning and during adult emergence and were expressed in the midgut, integument and head of molting larvae. The pupation and eclosion rates gradually decreased when the 1st-instar larvae were fed diets containing higher concentrations of the TH inhibitor 3-iodo-tyrosine (3-IT). Moreover, pupal weights were significantly decreased, and abnormal uncolored phenotypes were observed after 20 mg/g 3-IT was incorporated into the diet. In addition, the suppression of TH function (mediated by RNA interference) led to a decrease in TH mRNAs and eclosion rates, accompanied by less-pigmented phenotypes. There was a severe impairment of larval-pupal cuticle tanning, leading to pupae with less yellowish pigment or that were completely white and transparent, when we injected 2 µL of 24.4 mM or 73.27 mM 3-IT into 3rd-instar larvae or prepupae. These results suggest that TH is an important enzyme for the normal growth and pupal pigmentation of Z. tau and that TH is a potential gene target for use in the control of Z. tau.

Efficacy differences of electroacupuncture with single acupoint or matching acupoints for chemotherapy-induced nausea and vomiting: study protocol for a randomized controlled trial.

BACKGROUND: Previous studies have shown that acupuncture is beneficial for the alleviation of chemotherapy-induced nausea and vomiting. However, there is a lack of clinical evidence concerning the effects of acupoint-matching on chemotherapy-induced nausea and vomiting. METHODS/DESIGN: This is a parallel randomized controlled trial to evaluate the occurrence of nausea and vomiting after chemotherapy (the incidence of nausea and vomiting, frequency, VAS score, RINVR rating) as the main outcome for cancer. Quality of life, anxiety and depression scores are the secondary outcomes. Quality of life, anxiety and depression scores are the secondary phase. Use of remedy drugs, routine blood examination, and blood biochemical tests are the safety evaluation. We also compare the different effects of ST36 (single acupoint), CV12 (single acupoint), and ST36-CV12 matching groups. DISCUSSION: The results of this trial are expected to explore the effects of matching different acupoints and to offer biologic plausibility for the use of acupuncture in the treatment of chemotherapy-induced nausea and vomiting (CINV). TRIAL REGISTRATION: This trial is registered with clinicaltrials.gov NCT02195921 , The date of registration was 17 July 2014.

Influencing factors and interventional strategies for early enteral nutrition after gastric carcinoma surgery.

OBJECTIVE: The aim of this study is to investigate the factors influencing early enteral nutrition (EN) to develop guidelines after gastric carcinoma (GC) surgery, and to propose appropriate interventions. MATERIALS AND METHODS: A total of 118 GC patients have administrated EN 24 h after surgery and were divided into standard-achieving and nonstandard-achieving groups based on meeting 60% of energy needs. The clinical data of these two groups were retrospectively analyzed and compared. RESULTS: The intraoperative blood loss, proportion of those with body mass ≤60 kg, and those cases tolerating EN in the standard-achieving group were significantly greater than in the nonstandard-achieving group, and the differences were statistically significant (P < 0.05). Gender, age, operative time, catheter length, American Society of Anesthesiologists risk class, and postoperative exhaust time showed no statistically significant differences (P > 0.05). However, logistic regression analysis revealed that intraoperative blood loss, body mass, and EN tolerance were independent risk factors influencing achievement of standards for early postoperative EN in GC patients (P < 0.05). CONCLUSIONS: Individual differences should be considered when performing EN, and individualized nutritional support should be provided to improve the standard-achieving rate.

Crosstalk analysis of pathways in breast cancer using a network model based on overlapping differentially expressed genes.

Multiple signal transduction pathways can affect each other considerably through crosstalk. However, the presence and extent of this phenomenon have not been rigorously studied. The aim of the present study was to identify strong and normal interactions between pathways in breast cancer and determine the main pathway. Five sets of breast cancer data were downloaded from the high-throughput Gene Expression Omnibus (GEO) and analyzed to identify differentially expressed (DE) genes using the Rank Product (RankProd) method. A list of pathways with differential expression was obtained by gene set enrichment analysis (GSEA) of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The DE genes that overlapped between pathways were identified and a crosstalk network diagram based on the overlap of DE genes was constructed. A total of 1,464 DE genes and 26 pathways were identified. In addition, the number of DE genes that overlapped between specific pathways were determined, and the greatest degree of overlap was between the extracellular matrix (ECM)-receptor interaction and Focal adhesion pathways, which had 22 overlapping DE genes. Weighted pathway analysis of the crosstalk between pathways identified that Pathways in cancer was the main pathway in breast cancer.

[Identification of Nam Dinh virus in China].

During 2009-2012, the Nam Dinh virus (NDiv) was detected from the samples of Culex pipiens quinquefasciatus in Shenzhen China. In this study, cell culture,SYBR Green I based real time RT-PCR and RT-PCR were performed to analyze the cell susceptibility and other biological characteristics of the NDiV isolates. The results showed that C6/36 cell line was susceptible to four isolates of Culex pipiens quinquefasciatus. The "S" type amplification curve and specific melting curve were obtained in the realtime fluorescence quantitative RT-PCR based on SYBR Green I for the detection of the NDiV from the mosquito. The target bands from the RdRp gene and partial fragment of ZmHel1 gene were observed using agarose gel electrophoresis. Both the nucleotide and amino acid sequences of four Shenzhen isolates showed more than 99.00% homology with the Vietnam representative NDiV strain (02VN178). Phylogenetic analysis showed that four Shenzhen isolates shared the same evolution branch as the Vietnam representative NDiV strain. This is the first report of NDiV in China.

[Role of mass media during the severe acute respiratory syndrome epidemic].

OBJECTIVE: To understand the impact of effective interaction between public and media on the prevention and control of severe acute respiratory syndrome (SARS). METHODS: Based on the theory of field epidemiology, the traditional and modern technologies were brought forward. In the late period of SARS epidemic, investigation on knowledge, attitude and practice on SARS prevention and control among general population was conducted. RESULTS: During the 3 month period of SARS epidemic in Shenzhen, techniques of the "E-health and public health informatics" as an emerging fields were used to focus on population to eventually improve the health of entire population. Methods as television, radio, newspapers, magazines, printing and distribution of specific materials on SARS were included, and hotlines of telephone and mobile phone, web-based sites, electronic screening advertisements, and consultation or forum for the public etc. were used. Among 3405 subjects interviewed, more than 95% gave right answers on the SARS related questions. Most of them held the optimistic and scientific attitude. 80% of the population had taken the measures as recommended. 82.4% of the citizens were happy about the local government's action and 93.8% thought hospitals and healthcare workers should be respected and honored. CONCLUSION: Dealing with the urgent public health problems and emerging infectious diseases outbreak, epidemiologists need to keep good relations with media, and making use of modern electronic technologies to communicate with the public.