Proteomics and phosphoproteomics to study Tuina reverses capsule fibrosis in frozen shoulder: a research report based on rats.

Frozen shoulder (FS) is a common disorder often treated with Tuina, but the mechanisms involved remain unclear. We employed proteomics and phosphoproteomics to investigate the mechanisms associated with the treatment of capsule fibrosis in FS rats. We used a method composed of three weeks of cast immobilization to establish a model of FS. We then administered Tuina once daily for 14 days, evaluated glenohumeral range of motion (ROM), assessed histological changes, and identified differentially expressed proteins (DEPs) using proteomics and phosphoproteomics. This study demonstrated that Tuina could improve glenohumeral ROM and reserve capsule fibrosis in FS rats. Proteomics revealed proteins regulated by Tuina belonging to the PI3K-AKT and ECM receptor interaction signaling pathways. Phosphoproteomics detected differentially phosphorylated proteins regulated by Tuina to be enriched in the MAPK signaling pathway. The combination of proteomics and phosphoproteomics for Protein-Protein Interaction (PPI) network analysis revealed that the phosphorylation of Myh3 and Srsf1 with a node degree larger than the average degree were considered the central regulatory protein modulated by Tuina to reverse capsule fibrosis. Thbs1, Vtn, and Tenascin-W were significantly enriched in PI3K-AKT and ECM receptor interaction signaling pathways and highly expressed in model rats. Tuina resulted in reduced expression of these proteins. Our findings demonstrated some of mechanisms behind the reversal of FS capsule fibrosis following Tuina, a scientific medical therapy for FS patients.

Effect of exogenous bile salts supplementation on the performance and hepatic lipid metabolism of aged laying hens.

Bile acids (BA), a series of hydroxylated steroids secreted by the liver, are involved in the digestion and absorption of dietary fats. In the present study, the effect of exogenous BAs on the performance and liver lipid metabolism of laying hens was investigated. Three hundred and sixty 50-wk-old Hy-line Brown hens were randomly allocated into three groups and subjected to one of the following treatments: fed with the basal diet (control, Con), the basal diet supplemented with 0.1 g/kg (0.1 g/kg BAs), or 0.2 g/kg (0.2 g/kg BAs) porcine BAs. Laying performance, egg quality, and blood parameters were measured during the 8-wk experimental period. The expression of genes related to hepatic lipid metabolism was determined at the end of experiment. The results showed that BAs treatments had no influence (P > 0.05) on laying rate, egg weight, and feed efficiency. BAs treatment, however, significantly decreased mortality of hens (P = 0.006). BAs treatment showed a transient negative influence on eggshell quality at week 4 but not at week 8. The yolk color on week 8 was increased by BAs treatments (P < 0.0001) compared to control. The duodenum index showed a tendency to be increased (P = 0.053) and jejunum index were increased (P = 0.007) by BAs treatment. Compared to control, BAs treatments decreased lipid droplet content (P < 0.0001) and TG content (P = 0.002) of liver. Fatty acid synthase activity was also decreased as an effect of BAs dietary supplementation. Compared to the control group, 0.1 g/kg BAs treatment increased (P < 0.05) the mRNA expression of genes Farnesoid X receptor (FXR) (P = 0.042), cytochrome P450 family 7 subfamily A member 1 (CYP7A1) (P = 0.002), and cytochrome P450 family 8 subfamily B member 1 (CYP8B1) (P = 0.017), fatty acid synthase (FAS) (P = 0.020), acetyl-CoA carboxylase (ACC) (P = 0.032), sterol regulatory element binding protein-1c (SREBP-1c) (P = 0.037), proliferator-activated receptor gamma (PPARγ) (P = 0.002), apolipoprotein B (APO-B) (P = 0.020), and very low density lipoprotein receptor (VLDLR) (P = 0.024). In conclusion, the addition of exogenous BAs reduces lipid accumulation in liver. BA supplementation reduces the mortality of hens and improves egg yolk color, with no unfavorable effect on laying performance. The result suggests that suppressed FAS activity is involved in the reduced hepatic lipid accumulation by BAs treatment.

Fatty liver hemorrhagic syndrome is one of the most common diseases in laying hens and is a metabolic disease characterized by disorders of lipid metabolism in the liver, manifested by fatty liver degeneration and varying degrees of hemorrhage, which often occurs in caged hens in good condition and with high egg production rates. Bile acids (BA), a group of hydroxylated steroids synthesized from cholesterol in the liver, play an important role in lipid metabolism. This study aimed to examine the effects of dietary addition of different levels of BAs on the production performance and liver fat metabolism of 50-wk-old Hy-line Brown hens. The result indicates that the addition of exogenous BAs reduces lipid accumulation in liver. BAs supplementation reduces the mortality of hens and improves egg yolk color, with no other unfavorable side effects on laying performance. The results of the present study suggest that suppressed fatty acid synthase activity is involved in the reduced hepatic lipid accumulation as an effect of BAs dietary supplementation.

Tuina in a Frozen Shoulder Rat Model: An Efficient and Reproducible Protocol.

Frozen shoulder (FS) is a common condition with no defined optimal therapy. Tuina therapy, a traditional Chinese medicine (TCM) technique used to treat FS patients in Chinese hospitals, has demonstrated excellent results, but its mechanisms are not fully understood. Building on a previous study, this work aimed to develop a Tuina protocol for an FS rat model. We randomly divided 20 SD rats into control (C; n = 5), FS model (M; n = 5), FS model Tuina treatment (MT; n = 5), and FS model oral treatment (MO; n = 5) groups. This study used the cast immobilization method to establish the FS rat model. The effect of Tuina and oral dexamethasone on the glenohumeral range of motion (ROM) was evaluated, and the histological findings were assessed. Our study showed that Tuina and oral dexamethasone were able to improve shoulder active ROM and preserve the structure of the capsule, with Tuina therapy proving to be more effective than oral dexamethasone. In conclusion, the Tuina protocol established in this study was highly effective for FS.

Efficacy and safety of Tuina and intermediate frequency electrotherapy for frozen shoulder: MRI-based observation evidence.

BACKGROUND: Tuina and Intermediate Frequency (IF) electrotherapy are commonly used treatments for frozen shoulder (FS). This study aimed to compare the clinical efficacy of Tuina and IF electrotherapy in the treatment of stage II frozen shoulder and to provide evidence-based treatment for FS. METHODS: The FS patients were randomized into two groups, the observation group, which received Tuina, and the control group, which received IF electrotherapy. The total treatment duration was 20 minutes per treatment, 3 times per week; the treatment period was 6 weeks. Assessments were performed at baseline, 3 weeks, 6 weeks, and 16 weeks after follow-up. Primary assessments included visual analog scale (VAS), Constant-Murley scale (CMS), and secondary assessments included shoulder MRI, rotator cuff muscle diffusion tensor imaging (DTI). RESULTS: A total of 57 patients participated in this study, in the observation group (n = 29) and the control group (n = 28). At the end of the 3rd and 6th weeks of treatment, Tuina was significantly more effective than IF electrotherapy in reducing the VAS score and improving the Constant-Murley total score (P<0.05), but there was no significant difference in scores between the two groups at the 16-week follow-up (P>0.05). MRI results in both groups: compared to the control group, the observation group had better results in reducing the degree of periapical edema and reducing the thickness of the axillary humeral capsule (P<0.05); and the observation group had significantly more efficacy than the control group in improving the diffusion state of water molecules in the rotator cuff muscles (P<0.05). CONCLUSION: Tuina is more effective than IF electrotherapy in improving the symptoms of FS patients as it can rapidly relieve the pain and restore the function of the affected shoulder, reduce the edema of the shoulder capsule, restore the function of the rotator cuff muscles, and shorten the natural course of FS. Name of the registry: This study was registered in the Shandong University of Traditional Chinese Medicine Affiliated Hospital; Grant No. (2021) Lun Audit No. (033) - KY; Date of registration: 2021.4.27.

m6A RNA Methylation Regulators Contribute to Predict and as a Therapy Target of Pulmonary Fibrosis.

Background: Pulmonary fibrosis is difficult to treat. Early diagnosis and finding potential drug therapy targets of pulmonary fibrosis are particularly important. There were still various problems with existing pulmonary fibrosis markers, so it is particularly important to find new biomarkers and drug treatment targets. m6A (N6,2'-O-dimethyladenosine) RNA methylation was the cause of many diseases, and it is regulated by m6A methylation regulators. So, whether RNA methylation regulators can be a diagnostic marker and potential drug therapy target of early pulmonary fibrosis needs to be explored. Materials and Methods: Using GSE110147 and GSE33566 in the GEO database to predict the m6A methylation regulators that may be related to the development of pulmonary fibrosis, we used 10 mg/ml bleomycin to induce mouse pulmonary fibrosis models and human pulmonary fibrosis samples, to confirm whether this indicator can be an early diagnostic marker of pulmonary fibrosis. Results: According to the database prediction results, METTL3 can predict the occurrence and development of pulmonary fibrosis, and the results of MASSON and HE staining show that the fibrosis model of mice is successful, and the fibrosis of human samples is obvious. The results of immunohistochemistry showed that the expression of METTL3 was significantly reduced in pulmonary fibrosis. Conclusions: The m6A methylation regulator METTL3 can be considered as an important biomarker for diagnosing pulmonary fibrosis occurrence, furthermore it could be considered as a drug target because of its low expression in pulmonary fibrosis.

Revealing the magic of acupuncture based on biological mechanisms: A literature review.

Acupuncture has been used to treat various disease for more than 3,000 years in China and other Asian countries. As a complementary and alternative therapy, it has gained increasing popularity and acceptance among public and healthcare professionals in the West. Over the past few decades, basic and clinical research on acupuncture has made considerable progress. Internationally recognized evidence from clinical studies has been published, a preliminary system to clinically evaluate acupuncture has been created, and some clinical guidelines have been formulated. Moreover, scientists have strived to explore the physiological and biological mechanisms of acupuncture. Some basic studies have indicated that acupuncture has various actions, such as analgesic, muscle relaxing, anti-inflammatory, mild anxiolytic, and antidepressant actions, with possible biological mechanisms such as central sensitization, neurotransmitters, the intestinal flora, immune regulation, oxidative stress, and neuroinflammation. The current review describes the common indications for acupuncture recommended by the WHO and the use of acupuncture in China, the United States, Australia, and several other countries. This review then summarized the mechanisms by which acupuncture treats common conditions including lower back pain (LBP), ischemic stroke, depression, and irritable bowel syndrome (IBS) and it also cited specific acupuncture points for treating these conditions. The hope is that this review will provide useful information for both acupuncturists and researchers to better understand the mechanisms of acupuncture and reasons for its usage.

Applying QI-focused SPIDER approach to safer deprescribing for geriatric patients: Results of the Toronto Feasibility Study.

Context: More than 25% of Canadian seniors are prescribed 10+ different medications each year. There is a direct association between more medications and persistent high care needs/costs for seniors. Effective and appropriate deprescribing for seniors in primary care is needed. Objective: To present results of a feasibility study of the Structured Process Informed by Data, Evidence and Research (SPIDER) project aiming at improving safer deprescribing for complex older patients in community-based primary care. Study Design: Single-arm mixed methods study in Toronto, Ontario. Evaluation included participant interviews, focus groups, field notes and quantitative EMR data. Setting: Primary care practices affiliated with the University of Toronto Practice-Based Research Network (UTOPIAN). Population Studied: Patients aged 65+ years taking 10+ different medications. Intervention: 1) QI-focused Learning Collaboratives (LCs); 2) practice coaching; and 3) EMR data for audit & feedback. Outcome Measures: feasibility across eight dimensions: acceptability, demand, implementation, adaptation, integration, practicality, and efficacy. Results: Demand: 33 physicians and 24 allied health professionals from ten UTOPIAN practices and one community health centre participated in the Toronto LC. Implementation: the LC included a full day initial workshop, two short webinars, and a half-day summative congress over nine months. Practices had a monthly call with their QI coach and quarterly data reports. Adaptation, integration, practicality: teams developed various deprescribing tools and processes that were integratable to local context and existing practices. Acceptability: Teams perceived access to coaching as a valuable element of the approach. The initial review and validation of patients identified in the data reports were deemed time-consuming, particularly for under-resourced practices with a large cohort of target patient population. Access to pharmacist services and in-house QI and data support was considered two critical enablers to the sustainability of the approach. Efficacy: reductions in PIP prevalence and prevalence of patients with at least one PIP were 3.6% (p=.4) and 1.4% (p=.5), respectively. Conclusions: The SPIDER approach appears to be feasible. Access to coaching support and pharmacist services may enhance sustainability.

Genes Relevant to Tissue Response to Cancer Therapy Display Diurnal Variation in mRNA Expression in Human Oral Mucosa.

BACKGROUND: To address a critical gap for application of cancer chronotherapy of when would be the best time(s) for treating an individual cancer patient, we conducted a pilot study to characterize diurnal variations of gene expression in oral mucosal tissue, which is vulnerable to damage from cancer therapies. METHODS: We conducted RNA-seq assay on individual oral mucosal samples collected from 11 healthy volunteers every 4 hours (6 time points). Using a cosine-based method, we estimated the individual and average values of peak-time and amplitude for each gene. Correlations between gene expression peak-times and age was examined, adjusting for individual's sleep timing. RESULTS: Among candidate gene pathways that are relevant to treatment response, 7 of 16 genes (PER3, CIART, TEF, PER1, PER2, CRY2, ARNTL) involved in circadian regulation and 1 of 118 genes (WEE1) involved in cell cycle regulation achieved p-value ≤ 0.1 and relative amplitude>0.1. The average peak times were approximately 10:15 for PER3, CIART and TEF, 10:45 for PER1, 13:00 for WEE1, PER2 and CRY2, and 19:30 for ARNTL. Ranges in peak times across individuals differed by gene (e.g., 8 hours for PER1; 16.7 hours for WEE1). Older people had later peak times for PER1 (r = 0.77, p = 0.03) and PER3 (r = 0.69, p-value = 0.06). CONCLUSION: In oral mucosa, expression of some genes relevant to treatment response displayed diurnal variation. These genes may be candidates for development of biomarkers for optimizing individual timing of cancer therapy using non-invasively collected oral mucosa.

Raffinose synthase enhances drought tolerance through raffinose synthesis or galactinol hydrolysis in maize and Arabidopsis plants.

Raffinose and its precursor galactinol accumulate in plant leaves during abiotic stress. RAFFINOSE SYNTHASE (RAFS) catalyzes raffinose formation by transferring a galactosyl group of galactinol to sucrose. However, whether RAFS contributes to plant drought tolerance and, if so, by what mechanism remains unclear. In this study, we report that expression of RAFS from maize (or corn, Zea mays) (ZmRAFS) is induced by drought, heat, cold, and salinity stresses. We found that zmrafs mutant maize plants completely lack raffinose and hyper-accumulate galactinol and are more sensitive to drought stress than the corresponding null-segregant (NS) plants. This indicated that ZmRAFS and its product raffinose contribute to plant drought tolerance. ZmRAFS overexpression in Arabidopsis enhanced drought stress tolerance by increasing myo-inositol levels via ZmRAFS-mediated galactinol hydrolysis in the leaves due to sucrose insufficiency in leaf cells and also enhanced raffinose synthesis in the seeds. Supplementation of sucrose to detached leaves converted ZmRAFS from hydrolyzing galactinol to synthesizing raffinose. Taken together, we demonstrate that ZmRAFS enhances plant drought tolerance through either raffinose synthesis or galactinol hydrolysis, depending on sucrose availability in plant cells. These results provide new avenues to improve plant drought stress tolerance through manipulation of the raffinose anabolic pathway.

Magnesium reduces cadmium accumulation by decreasing the nitrate reductase-mediated nitric oxide production in Panax notoginseng roots.

Panax notoginseng is a traditional medicinal herb in China. However, the high capacity of its roots to accumulate cadmium (Cd) poses a potential risk to human health. Our previous study showed that nitrate reductase (NR)-dependent nitric oxide (NO) production promoted Cd accumulation in P. notoginseng root cell walls. In this study, the role of Mg in the regulation of NO production and Cd accumulation in P. notoginseng roots was characterized. Exposure of P. notoginseng roots to increasing concentrations of Cd resulted in a linear increase in NO production. The application of 2 mM Mg for 24 h significantly alleviated Cd-induced NO production and Cd accumulation in roots, which coincided with a significant decrease in the NR activity. Western analysis suggested that Mg increased the interaction between the 14-3-3 protein and NR, which might have been a reason for the Mg-mediated decrease in NR activity and NO production under Cd stress. These results suggested that Mg-mediated alleviation of Cd-induced NO production and Cd accumulation is achieved by enhancement of the interaction between the 14-3-3 protein and NR in P. notoginseng roots.

Antioxidant Activities and Repair Effects on Oxidatively Damaged HK-2 Cells of Tea Polysaccharides with Different Molecular Weights.

This study aims at investigating the antioxidant activity and repair effect of green tea polysaccharide (TPS) with different molecular weights (Mw) on damaged human kidney proximal tubular epithelial cells (HK-2). Scavenging activities on hydroxyl radical (·OH) and ABTS radical and reducing power of four kinds of TPS with Mw of 10.88 (TPS0), 8.16 (TPS1), 4.82 (TPS2), and 2.31 kDa (TPS3) were detected. A damaged cell model was established using 2.6 mmol/L oxalate to injure HK-2 cells. Then, different concentrations of TPSs were used to repair the damaged cells. Index changes of subcellular organelles of HK-2 cells were detected before and after repair. The four kinds of TPSs possessed radical scavenging activity and reducing power, wherein TPS2 with moderate Mw presented the strongest antioxidant activity. After repair by TPSs, cell morphology of damaged HK-2 cells was gradually restored to normal conditions. Reactive oxygen species production decreased, and mitochondrial membrane potential (Δψm) of repaired cells increased. Cells of G1 phase arrest were inhibited, and cell proportion in the S phase increased. Lysosome integrity improved, and cell apoptotic rates significantly reduced in the repaired group. The four kinds of TPSs with varying Mw displayed antioxidant activity and repair effect on the mitochondria, lysosomes, and intracellular DNA. TPS2, with moderate Mw, showed the strongest antioxidant activity and repair effect; it may become a potential drug for prevention and treatment of kidney stones.

Variations in fatty acid composition of Laoshan goat milk from partum to 135 days postpartum.

The objective of this study was to characterize the variations in fatty acid (FA) profile during 7 days of colostrum production and 5 months of mature milk production in Laoshan goats. The individual FA profiles of each sample were investigated by gas chromatography-mass spectrometry. Significant differences in FAs were found between colostrum and mature milk. The contents of saturated fatty acids (SFA), unsaturated fatty acids (UFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA), and sum of C6, C8, and C10 (SC6+C8+C10 ) were all significantly affected by lactation period. Furthermore, there was no significant difference in the ratio of UFA/SFA or C18:2 (cis9, cis12-octadecadienoic acid)/C18:3 (all cis-9,12,15-octadecatrienoic acid) during the lactation period. The highest concentrations of SC6+C8+C10 , UFA, MUFA, and PUFA appeared in colostrum, but the highest SFA content was in mature milk. The highest proportions of SC6+C8+C10 and SFA were 11.32% and 79.55% on 5th day and 135th day respectively. By contrast, the lowest proportion of UFA was 20.45% on the 135th day. C14:0 (10.93%-12.87%), C16:0 (27.54%-36.65%), C18:0 (10.47%-14.59%), and C18:1 (18.80%-30.61%) were the most predominant FAs in goat milk with significant differences during the 135 days lactation period except C18:0. In conclusion, the results of this study suggest that the lactation time has a pronounced effect on the FA compositions of goat milk.

Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21.

OBJECTIVE: Treg/Th17 imbalance plays an important role in rheumatoid arthritis (RA). Maresin 1 (MaR1) prompts inflammation resolution and regulates immune responses. We explored the effect of MaR1 on RA progression and investigated the correlation between MaR1 and Treg/Th17 balance. METHODS: Both patients with RA and healthy controls were recruited into the study. Collagen-induced arthritis (CIA) model was constructed to detect the clinical score, histopathological changes and Treg/Th17 ratio. Purified naive CD4+ T-cells were used to study the effect of MaR1 on its differentiation process and microRNA microarray studies were performed to investigate MaR1 downstream microRNAs in this process. MicroRNA transfection experiments were conducted by lentivirus to verify the mechanism of MaR1 on Treg/Th17 balance. RESULTS: Compared with controls, the MaR1 concentration was higher in the patients with inactive RA and lower in the patients with active RA. Expression of the Treg transcription factor FoxP3 was the highest in inactive RA and the lowest in active RA, while the Th17 transcription factor RORc showed a reverse trend. An inverse correlation was observed between the FoxP3/RORc ratio and Disease Activity Score 28. Intervention of MaR1 in the CIA model reduced joint inflammation and damage, and improved the imbalanced Treg/Th17 ratio. MaR1 increased Treg cells proportion while reduced Th17 cells proportion under specific differentiation conditions. Furthermore, miR-21 was verified as MaR1 downstream microRNA, which was upregulated by MaR1, modulating the Treg/Th17 balance and thus ameliorating the RA progression. CONCLUSIONS: MaR1 is a therapeutic target for RA, likely operating through effects on the imbalanced Treg/Th17 ratio found in the disease.

Intratumoral and Intertumoral Genomic Heterogeneity of Multifocal Localized Prostate Cancer Impacts Molecular Classifications and Genomic Prognosticators.

BACKGROUND: Next-generation sequencing is revealing genomic heterogeneity in localized prostate cancer (CaP). Incomplete sampling of CaP multiclonality has limited the implications for molecular subtyping, stratification, and systemic treatment. OBJECTIVE: To determine the impact of genomic and transcriptomic diversity within and among intraprostatic CaP foci on CaP molecular taxonomy, predictors of progression, and actionable therapeutic targets. DESIGN, SETTING, AND PARTICIPANTS: Four consecutive patients with clinically localized National Comprehensive Cancer Network intermediate- or high-risk CaP who did not receive neoadjuvant therapy underwent radical prostatectomy at Roswell Park Cancer Institute in June-July 2014. Presurgical information on CaP content and a customized tissue procurement procedure were used to isolate nonmicroscopic and noncontiguous CaP foci in radical prostatectomy specimens. Three cores were obtained from the index lesion and one core from smaller lesions. RNA and DNA were extracted simultaneously from 26 cores with ≥90% CaP content and analyzed using whole-exome sequencing, single-nucleotide polymorphism arrays, and RNA sequencing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Somatic mutations, copy number alternations, gene expression, gene fusions, and phylogeny were defined. The impact of genomic alterations on CaP molecular classification, gene sets measured in Oncotype DX, Prolaris, and Decipher assays, and androgen receptor activity among CaP cores was determined. RESULTS AND LIMITATIONS: There was considerable variability in genomic alterations among CaP cores, and between RNA- and DNA-based platforms. Heterogeneity was found in molecular grouping of individual CaP foci and the activity of gene sets underlying the assays for risk stratification and androgen receptor activity, and was validated in independent genomic data sets. Determination of the implications for clinical decision-making requires follow-up studies. CONCLUSIONS: Genomic make-up varies widely among CaP foci, so care should be taken when making treatment decisions based on a single biopsy or index lesions. PATIENT SUMMARY: We examined the molecular composition of individual cancers in a patient's prostate. We found a lot of genetic diversity among these cancers, and concluded that information from a single cancer biopsy is not sufficient to guide treatment decisions.

Antibacterial effects of Traditional Chinese Medicine monomers against Streptococcus pneumoniae via inhibiting pneumococcal histidine kinase (VicK).

Two-component systems (TCSs) have the potential to be an effective target of the antimicrobials, and thus received much attention in recent years. VicK/VicR is one of TCSs in Streptococcus pneumoniae (S. pneumoniae), which is essential for pneumococcal survival. We have previously obtained several Traditional Chinese Medicine monomers using a computer-based screening. In this study, either alone or in combination with penicillin, their antimicrobial activities were evaluated based on in vivo and in vitro assays. The results showed that the MICs of 5'-(Methylthio)-5'-deoxyadenosine, octanal 2, 4-dinitrophenylhydrazone, deoxyshikonin, kavahin, and dodecyl gallate against S. pneumoniae were 37.1, 38.5, 17, 68.5, and 21 µg/mL, respectively. Time-killing assays showed that these compounds elicited bactericidal effects against S. pneumoniae D39 strain, which led to a 6-log reduction in CFU after exposure to compounds at four times of the MIC for 24 h. The five compounds inhibited the growth of Streptococcus pyogenes, Streptococcus mitis, Streptococcus mutans or Streptococcus pseudopneumoniae, meanwhile, deoxyshikonin and dodecyl gallate displayed strong inhibitory activities against Staphylococcus aureus. These compounds showed no obvious cytotoxicity effects on Vero cells. Survival time of the mice infected by S. pneumoniae strains was prolonged by the treatment with the compounds. Importantly, all of the five compounds exerted antimicrobial effects against multidrug-resistant clinical strains of S. pneumoniae. Moreover, even at sub-MIC concentration, they inhibited cell division and biofilm formation. The five compounds all have enhancement effect on penicillin. Deoxyshikonin and dodecyl gallate showed significantly synergic antimicrobial activity with penicillin in vivo and in vitro, and effectively reduced nasopharyngeal and lung colonization caused by different penicillin-resistant pneumococcal serotypes. In addition, the two compounds also showed synergic antimicrobial activity with erythromycin and tetracycline. Taken together, our results suggest that these novel VicK inhibitors may be promising compounds against the pneumococcus, including penicillin-resistant strains.

[Meta-analysis on effect of compound Danshen injection in treating neonatal hypoxic-ischemic encephalopathy].

To systematically evaluate the clinical efficacy and safety of compound Danshen injection in treating hypoxic-ischemic encephalopathy (HIE) of newborns. Computer retrievals were made in PubMed, Embase, Cochrane Library, CBM, CNKI, VIP and China info (before May 2014) and relevant literature references, and manual retrievals were made for journals and conference papers, in order to collect randomized or semi-randomized controlled trials concerning compound Danshen injection in the treatment of neonatal HIE. The quality of included references was evaluated according to literatures recommended by Cochrane Handbook. RevMan 5. 3 software was applied in the statistical treatment. Finally, a total of 13 randomized controlled trials were included, covering 1,211 patients (including 639 patients in the compound Danshen injection-treated group and 572 patients in the control group). Meta-analysis results showed that the routine treatment combined with compound Danshen injection can improve the treatment efficiency of neonatal HIE [RR = 1.28; 95% CI (1.21-1.36)], reduce the mortality rate [RR = 0.42; 95% CI (0.23-0.75)] and the incidence of long-term neurological sequelae [RR = 0.48; 95% CI (0.35-0.65)], with statistical differences. No fatal side effect was observed in all of included trials. So far, limited evidences in this study proved that the application of compound Danshen injection in the treatment of neonatal HIE can enhance the clinical efficiency. However, because of the low quality of the included trials, more well-designed and large-scale multi-center randomized controlled trials shall be made in the future.

Reducing arsenic accumulation in rice grain through iron oxide amendment.

Effects of soil-arsenic (As), phosphorus and iron oxide on As accumulation in rice grain were investigated. Cultivars that have significantly different sensitivity to As, straighthead-resistant Zhe 733 and straighthead-susceptible Cocodrie, were used to represent different cultivar varieties. The grain accumulation of other elements of concern, selenium (Se), molybdenum (Mo), and cadmium (Cd) was also monitored. Results demonstrated that high soil-As not only resulted in high grain-As, but could also result in high grain-Se, and Zhe 733 had significantly less grain-As than Cocodrie did. However, soil-As did not impact grain-Mo and Cd. Among all elements monitored, iron oxide amendment significantly reduced grain-As for both cultivars, while the phosphate application only reduced grain-Se for Zhe 733. Results also indicated that cultivar type significantly impacted grain accumulation of all monitored trace elements. Therefore, applying iron oxide to As-contaminated land, in addition to choosing appropriate rice cultivar, can effectively reduce the grain accumulation of As.

[1:2 matched case-control study on the risk factors related to congenital heart disease during the peri-conceptional period].

OBJECTIVE: To explore the possible risk factors during the periconceptional period relevant on the occurrence of congenital heart diseases (CHD) in the offspring. METHODS: A 1:2 matched case-control study was designed. From January 2012 to January 2014 in a district from Wuhan city, HuBei province, children were proved by MCH institutions through the "free screening for congenital heart disease" program. Cases with CHD were screened out by conventional auscultation, echocardiography figure and confirmed by physicians from the high-level hospitals. According to age, gender, community paired healthy children were chosen as controls. EpiData 3.1 software was used to input data, using SPSS 11.5 software to analyze the possible risk factors under simple and multiple factors logistic regression. RESULTS: Information from parents of 138 cases and 276 controls was collected. 27 major factors from the conditional logistic regression analysis showed that factors as:mental stress during early pregnancy, calcium supplement in the early stage of pregnancy, pregnancy malnutrition, having histories of abnormal childbearing, women with multiparous experiences and residence nearby sources of pollution (enterprises) etc. were associated with the incidence of congenital heart disease in the offspring. Data from the multivariate logistic regression analysis showed that factors as:mental stress during early pregnancy (HR = 3.35, 95%CI: 1.28-8.79), pregnancy malnutrition during pregnancy (HR = 1.50, 95% CI:1.10-2.03) and with abnormal childbearing history (HR = 1.62, 95% CI:1.03-2.57) were risk factors. However, calcium supplement during early pregnancy (HR = 0.40, 95% CI:0.25-0.65) could reduce the risk of CHD. CONCLUSION: The occurrence of CHD might be related to factors as:mental stress during early pregnancy, calcium supplement during early pregnancy, pregnancy malnutrition and having histories of abnormal childbearing. Peri-conceptional care should be strengthened to reduce the incidence of congenital heart disease.

Anti-enterovirus 71 effects of chrysin and its phosphate ester.

Enterovirus 71 (EV71) can cause severe disease and even lead to death in children, and an effective antiviral drug is currently unavailable. The anti-EV71 effect of chrysin (5,7-dihydroxyflavone), a natural flavonoid commonly found in many plants, was tested in this report. By using the predicting program Autodock 4.0 and an in vitro protease inhibition assay, we found that chrysin could suppress viral 3Cpro activity. Replication of viral RNA and production of viral capsid protein and the infectious virion were strongly inhibited by chrysin, without noticeable cytotoxicity. Cytopathic effects on cells were also prevented. Diisopropyl chrysin-7-yl phosphate (CPI), the phosphate ester for chrysin, was generated through a simplified Atheron-Todd reaction to achieve stronger anti-viral activity. CPI was also able to bind with and inhibit viral 3Cpro activity in vitro. As expected, CPI demonstrated more potent antiviral activity against EV71.

Bromelain ameliorates the wound microenvironment and improves the healing of firearm wounds.

BACKGROUND: In a previous study, we proposed a new therapy using topical bromelain as a supplement to simple wound-track incision for the debridement of firearm wounds. This enzymatic debridement greatly simplified the management of high-velocity gunshot wounds in a pig model, and bromelain was confirmed to improve wound healing. The purpose of the present study was to investigate the effect of bromelain on the microenvironment of firearm wounds. METHODS: Sixteen Chinese landrace pigs wounded by high-velocity projectiles were divided randomly into four groups: wound incision (group I), incision + bromelain (group IB), wound excision (group E), and control. Blood perfusion, oxygen partial pressure (pO(2)), and the content of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-ß in wound-track tissue were measured. Wound healing was also noted. RESULTS: The recovery of blood perfusion in tissue and pO(2) in wound tracks was significantly more rapid in group IB and group E than in group I and control. The tissue level of TNF-α was significantly lower in group IB than in group I and control 48 h and 72 h post-wounding, and was lower than in group E 48 h post-wounding. The tissue level of TGF-ß in group IB was sustained at a significantly higher level than in the other three groups. Wound healing time was also shorter in group IB. CONCLUSIONS: Enzymatic debridement using topical bromelain in incised wound tracks accelerates the recovery of blood perfusion, pO(2) in wound tissue, controls the expression of TNF-α and raises the expression of TGF-ß.