ABSTRACT Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR. (DR involved Recently reninangiotensinaldosterone renin aldosterone (RAAS Ang II, , II) stress inflammation retina Therefore Notably hypertension Still studied review

Abstract Histone deacetylase 9 (HDAC9) is a histone deacetylase (HDAC) subtype IIa protein that deacetylates histone 3 (H3), histone 4 (H4), and nonhistone proteins in vivo to alter chromosomal shape and regulate gene transcription. There have been few studies on the regulatory influence of the HDAC9 gene on the differentiation of chicken embryonic stem cells (cESCs) into male germ cells, and the significance of HDAC9 is still unknown. Therefore, we explored the specific role of HDAC9 during differentiation of the cESCs of Jilin Luhua chickens through inhibition or overexpression. In medium supplemented with 10-5 mol/L retinoic acid (RA), cESCs were stimulated to develop into germ cells. HDAC9 and germline marker gene mRNA and protein levels were measured using qRT‒PCR and western blotting. During the differentiation of cESCs into male germ cells, overexpression of the HDAC9 gene greatly increased the mRNA and protein expression levels of the germline marker genes Stra8, Dazl, c-kit, and integrin ɑ6. The HDAC9 inhibitor TMP195 significantly decreased the mRNA and protein expression levels of the above markers. In summary, HDAC9 positively regulates the differentiation of cESCs. HDAC (HDAC9 (HDAC H3, H3 H , (H3) H4, H4 (H4) transcription (cESCs unknown Therefore 105 10 5 10- molL mol L RA, RA (RA) qRTPCR qRT PCR blotting Stra8 Stra Dazl ckit, ckit c kit, kit c-kit ɑ6 ɑ TMP TMP19 markers summary (H3 (H4 1 (RA TMP1 (H

Abstract The conversion of sesamin to asarinin is a promising route for the production of asarinin. This work reports the affection of acid type and strength of the catalyst on the conversion of sesamin to asarinin and the effect of various reaction conditions in anhydrous ethanol using phosphotungstic acid (HPW) as catalyst. The experimental results indicate that the activity of sesamin conversion is determined by strong B acids. L acids are not active for the reaction, and do not show synergy with B acids for the formation of asarinin. Reaction time, HPW dosage and temperature have significant effects on sesamin conversion. A maximum asarinin yield of 57.93% was achieved. The reaction kinetics in the temperature range 55-75 °C were studied. The kinetic curves can be successfully fitted with an opposing first-order reaction model. The activation energy (Ea) for this reaction is found to be 105.2 ± 0.4 kJ/mol. (HPW time 5793 57 93 57.93 achieved 5575 55 75 55-7 C studied firstorder first order model Ea (Ea 1052 105 2 105. 04 0 4 0. kJmol kJ mol kJ/mol 579 5 9 57.9 557 7 55- 10 57. 1

Abstract Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine, demonstrating an increasing incidence every year. TongXieYaoFang (TXYF) has been used widely in China as a complementary therapy to relieve the symptoms of IBD for hundreds of years. In the present research, a network pharmacology-based approach was used to systematically explore the intrinsic mechanisms of TXYF in IBD at the molecular level. Network pharmacology-based methods, which mainly included database mining, screening of bioactive compounds, target prediction, collection of IBD-related targets, gene enrichment analysis, network construction, and molecular docking, were employed in the present study. Network analysis revealed a total of 108 potential targets derived from 22 component compounds of TXYF, among which 34 targets were common with the IBD-related targets. In the protein-protein interaction (PPI) network, 10 key targets were identified. The gene enrichment analysis suggested that anti-inflammatory processes, such as NF-kappa B signaling pathway and Toll-like receptor signaling pathway, could be the core processes involved in the action of TXYF in IBD. Molecular docking results revealed that three compounds present in TXYF exhibited strong binding affinity for PTGS2. The present study provides novel insights into the molecular mechanisms and network approaches of TXYF action in IBD from a systemic perspective. The potential targets and pathways identified in the present study would assist in further research on the clinical application of TXYF in IBD therapy.

ABSTRACT Biolog Eco technology was used to investigate the effects of different chemical herbicide application methods, such as pre-emergence after sowing and post-emergence (stem and leaf spraying), on the characteristics of carbon source utilization by microbial communities in alfalfa rhizosphere soil. The averages of well color development (AWCD) and microbial metabolism diversity indices of post-emergence herbicide spraying on stems and leaves were significantly lower than those of pre-emergence herbicide and without herbicide treatments. Furthermore, pre-emergence after sowing herbicide treatment did not affect soil microorganisms. The principal component analysis (PCA) revealed that the microbial community diversities of the rhizosphere soils differed significantly between herbicide treatments. Carbohydrate was the carbon source type that was most sensitive to herbicide treatment changes, followed by amino acids and carboxylic acids. The herbicide application method significantly reduced the capacities of the microbial community to utilize the carbon sources, as mainly manifested in the ability to use polymers. As shown by a comprehensive analysis on the growth of alfalfa and the physiological and biochemical indices of its root system, the application of herbicide chlorimuron-ethyl reduced the alfalfa yield, and the two different application methods tested showed no significant difference. Herbicide application and different application methods showed significant impacts on alfalfa root activity and membrane permeability, suggesting that the application of herbicide damaged the membrane permeability and the activity of the alfalfa root system. Impacts of herbicide residues in the soil after stem and leaf post-emergence treatment on alfalfa growth and soil microorganisms should not be ignored.

Abstract S. miltiorrhiza is a Chinese medicinal plant that is widely cultivated. The root growth in S. miltiorrhiza are inhibited by soil salinity. Here we investigated the capability of a plant growth regulator, 5-ALA to promote the growth of S. miltiorrhiza under different salt stresses. Five-month old S. miltiorrhiza roots were uniformly irrigated with different levels of salt solution i.e. 0, 100, 200 mM NaCl. After 3 days of treatment, salt-treated S. miltiorrhiza plants were sprayed with different concentrations of ALA (0, 10 mg L-1, 20 mg L-1) on the leaves and cultured for another 7 days. Results revealed that ALA treated plants produced significantly higher biomass by sustaining leaf chlorophyll content under salt stressed. 10 mg L-1 ALA significantly up-regulated antioxidant enzymes activities under studied salinity treatments. Positive effects of ALA on antioxidant defense systems were also supported by a significant increase in the expression of SOD isoenzymes genes (CSD1, FSD1 and MSD2), defense response genes (DXS1, C4H, GGPPS) and stress-related gene (MYB36 , MYB39) of ALA treated plants. This study suggested that ALA can protect S. miltiorrhiza from salinity induced oxidative stress and injury by promoting antioxidant defense system, boosting secondary metabolic pathways and protecting photosynthetic pigments.

ABSTRACT Due to large-scale wetland reclamation, the typical wetland had been conversed to different wetland use types (upland field, paddy field, and artificial forest) in the Sanjiang Plain. However, there are scarce data regarding soil aggregates and active organic carbons during land-use transition. Here, soil aggregates and the changes in content and storage of active organic carbon [total organic carbon (TOC), dissolved organic carbon (DOC), microbial biomass carbon (MBC), and readily oxidized carbon (ROC)] were studied under three land-uses reclaiming wetlands as an upland field, paddy field, and artificial forest in Heilongjiang Province, China. The results showed that soil aggregate structure changed significantly under the three land-uses, of which the largest decrease of mean weight diameter (MWD) occurred in the upland field. Under the three land-use types, the content and storage of TOC and each active organic carbon in soil aggregates with different size fractions significantly decreased compared with that in the wetland. In addition, the proportion of the 1–2 mm soil aggregate was significantly lower than that of other particle sizes, which resulted in the lowest storage of TOC and active organic carbon at 1-2 mm and was found in the wetland, and different land-use types; small aggregates (<0.25 mm) with a small proportion were ignored in calculating organic carbon content and storage. The TOC and active organic carbon content in various soil aggregates varied significantly in different land-use types; the paddy field was most similar to the wetland because of seasonal flooding factors. In soil aggregates with various size fractions, the paddy field presented small changes in the TOC, DOC, and MBC content, and the ROC content was significantly lower than that in the upland field and the artificial forest land-use types. The TOC, DOC, and MBC content in the upland field and the artificial forest were significantly reduced compared with that in the paddy field due to the decrease of water content in the soil. In the artificial forest, which had less human disturbance, organic carbon content was less affected than in long-term cultivated upland fields due to its abundant plant root systems and large input of organic matter. The upland field could seriously affect the structure of soil aggregates and organic carbon in the wetlands and had the most negative impact on the wetland ecosystem.

Abstract Background: Interferon (IFN)-λ1, also named Interleukin (IL)-29, is a new member of the Type III IFN or IFN-λ family. IL-29 plays an important role in the pathogenesis of many types of autoimmune and inflammatory diseases. Objective: To study the role of IL-29 in the pathogenesis of psoriasis vulgaris. Methods: The authors detected the serum levels of IL-29 in forty-one patients with psoriasis vulgaris, twenty-three patients with atopic dermatitis and thirty-eight age and gender-matched controls by sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The effects of IL-29 on the expression of cytokines, such as IL-6, IL-17, IL-8, IL-4, IL10, Interferon (IFN-γ) and Tumor Necrosis Factor-α (TNF-α), in PBMCs and HaCat cells were determined by real-time quantitative PCR. Results: Our data indicated that serum IL-29 levels were significantly elevated in patients with psoriasis vulgaris when compared with atopic dermatitis patients and the control group. Moreover, Serum levels of IL-29 were closely associated with the severity of psoriasis vulgaris. Furthermore, IL-29 up-regulated the mRNA expression levels of IL-6, IL-17 and TNF-α in PBMCs from psoriasis vulgaris patients. In addition, IL-29 enhanced the IL-6 and IL-8 expression from the HaCat cells. Conclusion: This study provides the first observations on the association of IL-29 and psoriasis vulgaris and showed elevated IL-29 serum levels. The authors suggest that IL-29 may play a role in the pathogenesis of psoriasis vulgaris.

This study aimed to perform a meta-analysis to determine the efficacy and safety of emricasan. Nine databases were searched for clinical trials investigating the efficacy of emricasan treatment in patients with liver cirrhosis or fibrosis. A manual search was conducted to identify the missing trials. The quality of the included studies was assessed using the revised Cochrane risk of bias tool. Efficacy of emricasan treatment was defined as a positive change in apoptosis-related parameters from baseline to the last follow-up visit. Overall, emricasan treatment is more effective in patients with liver cirrhosis or fibrosis than placebo (standardized mean difference [SMD] [95% confidence intervals (CI)]=0.28 [0.14; 0.41]). No significant change in model for end-stage liver disease (MELD) score between the emricasan and placebo groups was noted (SMD [95% CI]=0.18 [-0.01; 0.36]; p=0.058). A 50 mg dose of emricasan had the highest efficacy rate compared to placebo (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012), followed by the 5 mg dosing regimen (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012). Treatment with emricasan resulted in significant reductions in ALT (mean difference (MD) [95% CI]=-5.89 [-10.59; -1.20]; p=0.014) and caspase3/7 levels (MD [95%CI]=-1215.93 [-1238.53; -1193.33]; p<0.001), respectively. No significant increase in the rate of overall adverse events was noted (OR [95% CI]=1.52 [0.97; 2.37]; p=0.069). Treatment with emricasan is more effective in improving liver function and apoptosis parameters compared to placebo, with a well-tolerated safety profile. However, due to the poor quality of the analyzed studies, the small number of trials and patients, and the short follow-up periods, more robust trials are still warranted.

Abstract Background Gastroesophageal reflux is a major complication of post-POEM (peroral endoscopic myotomy, POEM) for esophageal achlasia. Objective: To discuss the effects of three measuring methods for Gastroesophageal Reflux of Post-POEM Achalasia Patients and find out the best method for diagnosing post-POEM gastroesophageal reflux of esophageal achalasia patients by conducting clinical follow-up studies. Methods: Follow-up visits were conducted on the patients with esophageal achalasia who had received POEM treatment in our hospital from 2013 to 2016. Between 2 to 4 weeks post operation, Eckardt score was adopted to evaluate the operation efficacy, the GerdQ score, electronic gastroscopy and 24h esophagus impedance-pH monitoring to investigate the gastroesophageal reflux and the comparison of detection rate among the three different methods on post-POEM gastroesophageal reflux. Results: There were 76 patients with Eckardt scores were 3 or lower than 3 post POEM (76/78, 97.44%), 2 patients with Eckardt scores were 4 or higher than 4 (2/78, 2.56%), the cure rate of the treatment was as high as 97.44%; the Eckardt score post operation decreased more significantly than before operation, P<0.0.5. Conclusion: for post-POEM Achalasia patients, 24h esophagus impedance-pH monitoring is the best way to diagnose post-POEM gastroesophageal reflux.

Resumo Introdução: Perda auditiva induzida por ruído é uma das principais doenças ocupacionais causadas pela interação gene-ambiente. O Grainy Like 2, ou GRHL2 é um gene que tem sido considerado como candidato. Nesse sentido, muitos estudos avaliaram a associação entre o GRHL2 e perda auditiva induzida por ruído, embora os resultados sejam ambíguos e conflitantes. Objetivo: Identificar uma estimativa precisa da associação entre o polimorfismo rs3735715 no gene GRHL2 e a suscetibilidade à perda auditiva induzida por ruído. Método: Uma pesquisa abrangente foi feita para coletar dados até 8 de julho de 2018. No fim, quatro artigos elegíveis foram incluídos nesta metanálise, abrangeram 2.410 indivíduos. As odds ratios agrupadas com intervalos de confiança de 95% foram usadas para avaliar a força da associação. Resultados: Uma associação significante foi encontrada na população geral no modelo de dominância (GA/AA vs. GG, odds ratio = 0,707, intervalo de confiança 95% = 0,594-0,841) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,189, intervalo de confiança 95% = 1,062 a 1,333). Quando estratificados pelo local de trabalho dos indivíduos, também encontramos associação entre rs3735715 e risco de perda auditiva induzida por ruído no modelo de dominância (GA/AA vs. GG, odds ratio = 0,634, intervalo de confiança 95% = 0,514 ± 0,783) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,206, intervalo de confiança 95% = 1,054- 1,379). Conclusão: O polimorfismo Rs3735715 no gene GRHL2 pode influenciar a suscetibilidade à perda auditiva induzida por ruído. Estudos adicionais, amplos, bem desenhados e funcionais são necessários para confirmar essa associação em diferentes populações.

Abstract Instruction: Noise-induced hearing loss is a leading occupational disease caused by gene-environment interaction. The Grainy Like 2, GRHL2, is a candidate gene. In this regard, many studies have evaluated the association between GRHL2 and noise-induced hearing loss, although the results are ambiguous and conflicting. Objective: The purpose of this study was to identify a precise estimation of the association between rs3735715 polymorphism in GRHL2 gene and susceptibility of noise-induced hearing loss. Methods: A comprehensive search was performed to collect data up to July 8, 2018. Finally, 4 eligible articles were included in this meta-analysis comprising 2410 subjects. The pooled odds ratios with 95% confidence intervals were used to evaluate the strength of the association. Results: Significant association was found in the overall population in the dominant model (GA/AA vs. GG, odds ratio = 0.707, 95% confidence interval = 0.594-0.841) and allele model (G allele vs. A allele, odds ratio = 1.189, 95% confidence interval = 1.062-1.333). When stratified by source of the subjects, we also found association between rs3735715 and noise-induced hearing loss risk in the dominant model (GA/AA vs. GG, odds ratio = 0.634, 95% confidence interval = 0.514-0.783) and allele model (G allele vs. A allele, odds ratio = 1.206, 95% confidence interval = 1.054-1.379). Conclusion: Rs3735715 polymorphism in GRHL2 gene may influence the susceptibility of noise-induced hearing loss. Additional large, well-designed and functional studies are needed to confirm this association in different populations.

RESUMO OBJETIVO Comparar duas combinações de agentes olfativos para uso em terapia de treinamento olfativo no tratamento de disfunção olfatória após infecção do trato respiratório superior (ITRS) e investigar os fatores que influenciam os efeitos clínicos. METODOLOGIA 125 pacientes com disfunção olfativa foram divididos aleatoriamente em dois grupos: teste e controle. Durante o treinamento olfativo, quatro odores foram utilizados em ambos os grupos. O treinamento olfativo durou 24 semanas. Em seguida, os participantes foram testados usando Sniffin’ Sticks e o escore de discriminação, limiar e identificação (TDI) antes do tratamento e 1, 3 e 6 meses após o ele. Os escores de TDI foram comparados em momentos diferentes, entre os grupos e dentro deles, e os fatores de influência foram analisados. RESULTADOS Não houve diferença significativa nos escores de TDI entre os dois grupos. Além disso, os escores de TDI não demonstração nenhuma alteração significa após um mês de tratamento em ambos os grupos. Após 3 e 6 meses de tratamento, ambos os escores de TDI aumentaram significativamente, e as habilidades de identificação e discriminação de odores melhoraram significativamente em ambos os grupos; contudo, os limiares de odor não demonstraram melhora. O curso da doença foi um importante fator de influência no efeito terapêutico do treinamento olfativo em ambos os grupos. CONCLUSÃO A combinação de bálsamo essencial, vinagre, álcool, e perfume de rosas no treinamento olfativo, todos aromas comumente encontrados na vida cotidiana, podem efetivamente curar disfunção olfativa induzida por ITRS e melhorar significativamente as habilidades de discriminação e identificação de odores. Além disso, a prolongamento do tempo de tratamento pode ajudar na recuperação das funções olfativas, e o início antecipado do treinamento olfativo pode melhorar o efeito terapêutico.

SUMMARY OBJECTIVE To compare two combinations of olfactory agents for olfactory training therapy of olfactory dysfunction after upper respiratory tract infection (URTI) and investigate the influencing factors on clinical effects. METHODS 125 patients with olfactory dysfunction were randomly divided into two groups: test and control. During the olfactory training, four odors were used in both groups. The olfactory training lasted for 24 weeks. Then, participants were tested using Sniffin’ Sticks and threshold-discrimination-identification (TDI) composite scoring before treatment and at 1, 3, and 6 months after treatment. The TDI scores were compared at different time points between the groups and within them, and influence factors were analyzed. RESULTS There was no significant difference in TDI scores between both groups. Furthermore, TDI scores did not significantly change after one month of treatment in either of the groups. After 3 and 6 months of treatment, TDI scores both significantly increased, and the odor discrimination and identification abilities significantly strengthened in both groups; however, the odor thresholds did not improve. The course of the disease was a significant influencing factor on the therapeutic effect of olfactory training for both groups. CONCLUSION The combination of essential balm, vinegar, alcohol, and rose perfume for olfactory training, which are scents commonly found in daily life, can effectively cure URTI-induced olfactory dysfunction, and significantly improve the odor discrimination and identification abilities. Furthermore, prolonging the treatment time can help with the recovery of olfactory functions, and earlier olfactory training can improve the therapeutic effect.

The aim of this study was to investigate the influence of enhanced external counterpulsation (EECP) on the cardiac function of beagle dogs after prolonged ventricular fibrillation. Twenty-four adult male beagles were randomly divided into control and EECP groups. Ventricular fibrillation was induced in the animals for 12 min, followed by 2 min of cardiopulmonary resuscitation. They then received EECP therapy for 4 h (EECP group) or not (control group). The hemodynamics was monitored using the PiCCO2 system. Blood gas and hemorheology were assessed at baseline and at 1, 2, and 4 h after return of spontaneous circulation (ROSC). The myocardial blood flow (MBF) was quantified by 18F-flurpiridaz PET myocardial perfusion imaging at baseline and 4 h after ROSC. Survival time of the animals was recorded within 24 h. Ventricular fibrillation was successfully induced in all animals, and they achieved ROSC after cardiopulmonary resuscitation. Survival time of the control group was shorter than that of the EECP group [median of 8 h (min 8 h, max 21 h) vs median of 24 h (min 16 h, max 24 h) (Kaplan Meyer plot analysis, P=0.0152). EECP improved blood gas analysis findings and increased the coronary perfusion pressure and MBF value. EECP also improved the cardiac function of Beagles after ROSC in multiple aspects, significantly increased blood flow velocity, and decreased plasma viscosity, erythrocyte aggregation index, and hematocrit levels. EECP improved the hemodynamics of beagle dogs and increased MBF, subsequently improving cardiac function and ultimately improving the survival time of animals after ROSC.

Breast cancer (BC) is a commonly diagnosed cancer in females. MicroRNA-660-5p (miR-660-5p) has been reported to be involved in the occurrence and development of BC. However, the regulatory network of miR-660-5p in BC has not been fully addressed. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the enrichment of miR-660-5p and tet-eleven translocation 2 (TET2) in BC tissues and cells. Cell counting kit-8 (CCK8), flow cytometry, and transwell migration and invasion assays were used to measure cell proliferation, apoptosis, migration, and invasion. The target relationship between miR-660-5p and TET2 was confirmed by dual luciferase reporter assay. Protein expression was measured by western blot. The expression of miR-660-5p was elevated in BC, and high expression of miR-660-5p was closely related to lymph node metastasis, advanced TNM stage, and vascular invasion of BC tumors. miR-660-5p silencing inhibited cell proliferation and metastasis, but induced apoptosis of BC cells. TET2 was identified as a direct target of miR-660-5p, and the interference of TET2 partly reversed the suppressive effects of miR-660-5p silencing on the malignant potential of BC cells. miR-660-5p promoted BC progression partly through modulating TET2 and PI3K/AKT/mTOR signaling. miR-660-5p/TET2 axis might be a promising target for BC treatment.