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Objective To determine the time point when porcine pancreatic elastase(PPE)induced abdominal aortic aneurysm(AAA)reaches the regression phase in mice and observe the histological characteristics of AAA in regression phase.Methods AAAs were induced by transient intraluminal infusion of PPE in C57BL/6J mice.The diameters of the mouse abdominal aortas were measured before PPE infusion and sacrifice time,day 14 for AAA progression phase or day 56 for regression phase after PPE infusion,respectively.The histological characteristics of the aneurysm lesion site on day 14 and day 56 after surgery were compared and analyzed.Results The diameters of the abdominal aortas were significantly increased in both day 14 and day 56 after PPE infusion groups(diameter growth rate 147%and 155%,respectively)as compared to the baseline diameters.In the day 14 group,the infused aortas showed typical AAA characteristics,such as elastin break/degradation,medial smooth muscle cells depletion,and inflammatory cell diffused infiltration.In the day 56 group after PPE infusion,although the artery diameter did not change significantly as compared to the day 14 group,histology showed that elastin was partially repaired,new smooth muscle cells were added to the damaged aorta media,the infiltrated inflammatory cells were significantly subsided,and the adventitia neovascularization was reduced,showing a significant feature of the disease regression phase.Conclusion In the PPE-induced mouse AAA model,day 56 after surgery is an appropriate time point for observing aneurysm regression,and the histological characteristics of the regression are obvious.
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This article combs and summarizes the entire process of rare disease selection and priority theme determination, including the application and preliminary review of rare diseases, standardization of disease theme information, the evaluation methods of evidence sorting and disease selection for priority selection of disease themes, and other aspects of the content were analyzed in depth. It is expected to provide reference for the subsequent selection of rare diseases, improve the fairness, rationality and scientificity of rare disease selection, and further promote research and decision-making in China′s rare disease-related fields.
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Objective To analyze the effect of the fixed-jaw technique on dosimetric parameters during dynamic intensity-modulated radiotherapy (DIMRT) planning. Methods Ten patients each with nasopharyngeal carcinoma, postoperative cervical cancer, and right breast cancer after radical surgery were selected for this study; all patients underwent DIMRT in our hospital in 2020. After administration at the prescribed dose, two methods were used to design the radiotherapy plan for each patient: split-field technique (SFT) and fixed-jaw technique (FJT). The two plans were compared for the differences in the dosimetric parameters and plan verification pass rate. Results Compared with SFT, FJT showed significant decreases (P <0.05) in the following parameters for patients with nasopharyngeal carcinoma, postoperative cervical cancer, and right breast cancer after radical surgery: number of radiation fields (down by 41.5%, 47.3%, and 34.9%, respectively, t = 7.954, 24.2, and 4.949, respectively), total number of monitor units (MUs) (down by 5.6%, 5.3%, and 13.5%, respectively, t = 3.211, 2.423, and 5.481, respectively), and actual beam-on time (down by 25.3%, 23.8%, and 13.6%, respectively, t = 5.814, 9.208, and 5.655, respectively). There were significant differences in some of the dosimetric parameters for all three types of cancer patients between the two plans (P <0.05). There were no significant differences in the plan verification pass rate (P >0.05). Conclusion FJT can reduce the total number of MUs and actual beam-on time while meeting the requirements for clinically prescribed doses in DIMRT planning.
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Biorefinery of chemicals from straw is an effective approach to alleviate the environmental pollution caused by straw burning. In this paper, we prepared gellan gum immobilized Lactobacillus bulgaricus T15 gel beads (LA-GAGR-T15 gel beads), characterized their properties, and established a continuous cell recycle fermentation process for D-lactate (D-LA) production using the LA-GAGR-T15 gel beads. The fracture stress of LA-GAGR-T15 gel beads was (91.68±0.11) kPa, which was 125.12% higher than that of the calcium alginate immobilized T15 gel beads (calcium alginate-T15 gel beads). This indicated that the strength of LA-GAGR-T15 gel beads was stronger, and the strain was less likely to leak out. The average D-LA production was (72.90±2.79) g/L after fermentation for ten recycles (720 h) using LA-GAGR-T15 gel beads as the starting strain and glucose as the substrate, which was 33.85% higher than that of calcium alginate-T15 gel beads and 37.70% higher than that of free T15. Subsequently, glucose was replaced by enzymatically hydrolyzed corn straw and fermented for ten recycles (240 h) using LA-GAGR-T15 gel beads. The yield of D-LA reached (1.74±0.79) g/(L·h), which was much higher than that of using free bacteria. The wear rate of gel beads was less than 5% after ten recycles, which indicated that LA-GAGR is a good carrier for cell immobilization and can be widely used in industrial fermentation. This study provides basic data for the industrial production of D-LA using cell-recycled fermentation, and provides a new way for the biorefinery of D-LA from corn straw.
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Fermentation , Lactobacillus delbrueckii , Zea mays , Lactic Acid , Alginates/chemistry , GlucoseABSTRACT
Abscisic acid, a plant hormone that inhibits growth, is a key factor in balancing plant endogenous hormones and regulating growth and metabolism. Abscisic acid can improve the drought resistance and salt tolerance of crops, reduce fruit browning, reduce the incidence rate of malaria and stimulate insulin secretion, so it has a broad application potential in agriculture and medicine. Compared with traditional plant extraction and chemical synthesis, abscisic acid synthesis by microorganisms is an economic and sustainable route. At present, a lot of progress has been made in the synthesis of abscisic acid by natural microorganisms such as Botrytis cinerea and Cercospora rosea, while the research on the synthesis of abscisic acid by engineered microorganisms is rarely reported. Saccharomyces cerevisiae, Yarrowia lipolytica and Escherichia coli are common hosts for heterologous synthesis of natural products due to their advantages of clear genetic background, easy operation and friendliness for industrial production. Therefore, the heterologous synthesis of abscisic acid by microorganisms is a more promising production method. The author reviews the research on the heterologous synthesis of abscisic acid by microorganisms from five aspects: selection of chassis cells, screening and expression enhancement of key enzymes, regulation of cofactors, enhancement of precursor supply and promotion of abscisic acid efflux. Finally, the future development direction of this field is prospected.
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Abscisic Acid/metabolism , Plant Growth Regulators/metabolism , Plants/metabolism , Yarrowia/metabolismABSTRACT
Helicobacter pylori (Hp) is one of most common pathogens causing gastrointestinal disorder including gastric ulcer, duodenal ulcer and gastric cancer, etc. It has been verified as class I carcinogen by WHO. Nowadays, combination antibiotics and proton pump inhibitor are mainly used to erase Hp in clinical application. However, with the increased resistance of Hp, the vaccine against Hp might become the best strategy to eradicate Hp. Elements including urease, virulence factor, outer membrane protein, flagella, play an important role in Hp infection, colonization and reproduction. They have become potential candidate antigens in the development of Hp vaccine, as reported in previous studies. Presently, these antigens-centric vaccines have been tested in animal models. Therefore, this article reviews the studies on Hp vaccine with urease, virulence genes, outer membrane protein and flagella as their candidate antigens, in an attempt to provide insights for research in this regard.
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Animals , Helicobacter pylori , Urease/genetics , Helicobacter Infections/prevention & control , Vaccines , Membrane ProteinsABSTRACT
Objective To investigate the inhibitory effect of ursolic acid in Hippophae rhamnoides L. on hepatocyte apoptosis in rats with alcoholic liver disease based on the mitochondria-cytochrome c pathway. Methods A total of 50 specific pathogen-free male Wistar rats were divided into normal control group, alcohol model group, and low-, middle-, and high-dose ursolic acid groups using a random number table, with 10 rats in each group. The rats in the normal control group were given normal saline by gavage once a day for 8 weeks; the rats in the alcohol model group were given alcohol at increasing concentrations by gavage for 8 consecutive weeks; the rats in the low-, middle-, and high-dose ursolic acid groups were given ursolic acid at a dose of 50, 100, and 150 mg/kg, respectively, followed by an equal volume of alcohol as the model group 1 hour later. Serum liver function parameters were measured for each group; HE staining was used to observe liver histopathology; an electron microscope was used to observe hepatocyte ultrastructure; the TUNEL method was used to measure hepatocyte apoptosis; Western Blotting was used to measure the protein expression levels of cytochrome c and activated caspase-3 in hepatocyte mitochondria and cytoplasm. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the alcohol model group, the middle- and high-dose ursolic acid groups had significant reductions in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase (all P < 0.05). The rats in the alcohol model group had disordered arrangement of hepatic cords with marked hepatocyte edema and fatty degeneration, while those in the middle- and high- dose ursolic acid groups had basically normal arrangement of hepatic cords and a significant improvement in hepatocyte fatty degeneration, as well as a significant increase in the number of hepatocyte mitochondria and a significant improvement in morphology. Compared with the alcohol model group, the middle- and high-dose ursolic acid groups had significantly lower hepatocyte apoptosis rate and protein expression levels of cytochrome c and caspase-3 in cytoplasm (all P < 0.05). Conclusion Ursolic acid in Hippophae rhamnoides L. can improve the liver function and histomorphology of rats with alcoholic liver disease, possibly by inhibiting the release of cytochrome c in hepatocyte mitochondria, the activation of caspase-3, and the apoptosis of hepatocytes via the mitochondria-cytochrome c pathway.
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The National Health Commission of the People′s Republic of China and six other departments jointly released the Second Catalog of Rare Diseases, which expanded the definition of rare diseases in China. The expansion of the catalog means greater attention to rare diseases at the national level, and is also expected to accelerate the launch of relevant rare disease drugs and benefit more rare disease patients. When the new rare disease catalog released, it is necessary to quickly sort out the availability of drugs and find out the base number for the advancement of subsequent relevant measures. This paper searched official medical information websites and medical databases such as the National Medical Products Administration (NMPA), the Center for Drug Evaluation (CDE), and foreign drug regulatory agencies, and sorted out and summarized the subject categories of diseases included in the Second Catalog of Rare Diseases, the corresponding global research and development and implementation of drugs, as well as the medical insurance access situation in China, elaborates on the differences in the accessibility of orphan drugs at home and abroad. As China′s prevention, treatment and protection of rare diseases has reached a new point, plans and prospects are made for the introduction of relevant policies in the future, as well as the promotion of research and development and protection and other key tasks.
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In this article, methods of measuring and evaluating treatment adherence, based on whether they are objective and subjective, are reviewed upon literature examination, and the advantages and disadvantages of each method for different population segments are also discussed.It is intended to provide medical professionals and researchers with a general framework about adherence assessment methods.During treatment and research, medical professionals and researchers should select the most appropriate methods for their purposes and provide effective and personalized evaluation methods to ultimately evaluate and improve patients' medication adherence.
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Adenosine triphosphate (ATP) regeneration systems are essential for efficient biocatalytic phosphoryl transfer reactions. Polyphosphate kinase (PPK) is a versatile enzyme that can transfer phosphate groups among adenosine monophosphate (AMP), adenosine diphosphate (ADP), ATP, and polyphosphate (Poly P). Utilization of PPK is an attractive solution to address the problem of ATP regeneration due to its ability to use a variety of inexpensive and stable Poly P salts as phosphate group donors. This review comprehensively summarizes the structural characteristics and catalytic mechanisms of different types of PPKs, as well as the variations in enzyme activity, catalytic efficiency, stability, and coenzyme preference observed in PPKs from different sources. Moreover, recent advances in PPK-mediated ATP regeneration systems and protein engineering of wild-type PPK are summarized.
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Adenosine Triphosphate/metabolism , Adenosine Monophosphate , Polyphosphates/metabolism , Catalysis , RegenerationABSTRACT
Objective To compare the diagnostic performance of PI-RADS v2.1 and PI-RADS v2 in the detection of clinically significant prostate cancer(csPCa) by Meta-analysis. Methods The major biomedical databases were searched (CNKI, CBM, Medline, and Embase) with the keywords "PIRADS v2.1" or "PI-RADS v2.1". The Quality Assessment of Diagnostic Accuracy Studies Tool v2 (QUADAS-2) was used to evaluate literature quality. Meta-analysis was performed using STATA17.0 and ReMan5.4 software. Forest plots were used to represent the sensitivity and specificity of PI-RADS v2.1 and PI-RADS v2 for each study. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were combined, and diagnostic performance was evaluated using asummary receiver operating characteristic curve (SROC). Subgroup analysis was performed on three covariables: tumor location, threshold, and the nationality of authors. Results A total of 12 studies were included, involving 3 158 patients and 3 243 lesions. Forall zones and the whole gland, PI-RADS v2.1 had a larger area under the SROC curve (AUC) for csPCa performance, compared with PI-RADS v2. Subgroup analysis: PI-RADS v2.1 also had a larger area under the SROC (AUC) to detect transitional zone csPCa. Different diagnostic thresholds: when a score of 4 was used for the threshold, PI-RADS v2.1 had the maximum area under SROC (AUC) for csPCa performance detection. Author nationality: Researches of PI-RADS v2.1 in Chinese authors had the largest area under the SROC (AUC) in detecting csPCa performance. Conclusion Compared with PI-RADS v2, the diagnostic performance of PI-RADS v2.1 in detecting csPCa is not obviously improved and overall specificity is still low.
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Objective To investigate the effect of NAIF1 in gastric cancer cell lines MKN45. Methods We constructed pLVX-Tight-Flag-NAIF1-puro plasmid with Tet-on system. DOX was added to induce NAIF1 expression in MKN45 cells. The cells were collected at 0, 6, 12 and 24 hours after DOX addition for gene expression microarray detection and biological analysis of differentially expressed genes. qRT-PCR and Western blot were used to verify the changes in mRNA and protein levels of the selected target differential genes. Results The biological analysis of gene microarray hybridization results showed that IFIT1, IFIT2 and IFIT3 expression significantly increased at 24h, qRT-PCR also showed this change, and Western blot further verified the change in protein level. However, IFIT5 showed no significant change in mRNA and gene expression. Conclusion Over-expression of NAIF1 in gastric cancer cells can promote the expression of some immune system-related IFIT family proteins.
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Hypoxic ischemia (HI) is a fatal cause of neonatal encephalopathy and death. The developing brain can adjust the structures and function of brain according to different states due to neural plasticity. Understanding the pathophysiological process and cerebral network reorganization of neural damage after HI is very important for early diagnosis and intervention of disease. The research progresses of mechanism of neonatal cerebral network reorganization following HI were reviewed in this article.
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OBJECTIVE:To pro vide suggestions for imp roving the quality of ethical review of drug clinical trials in China and protecting the rights and interests of subjects. METHODS :Guided by risk management theory ,the literature research method , expert opinion method and analytic hierarchy process method were used to sort out the ethical review process of drug clinical trials , extract and determine the risk factors that affect the quality of ethical review ,and determine the weight of each risk factor. Suggestions were put forward improving the ethical review of drug clinical trials in China. RESULTS & CONCLUSIONS : Established ethical review risk index system of drug clinical trials included 31 influential factors of 5 aspects;the order of importance(weights)of 5 aspects affecting the quality of ethical review of drug clinical trials was as follows :the construction of the medical ethics committee (0.263 5),the management of review meetings (0.251 4),follow-up review (0.194 5),the acceptance and processing of review applications (0.189 2),and the management of documents and files (0.101 4). The influential factors with high weight included “withdrawal of people with conflict of interest in the discussion and voting process (0.078 7)” “timely review or conference discussion of scheme modification ,informed consent modification ,serious adverse events ,etc. (0.070 5)”“clarification and external exhibition of the work process and time of ethical review (0.059 8)”“unified and standardized review standards and approval standards (0.052 1)”,etc. The quality of ethical review can be improved by avoiding people with conflict of interest in the discussion and voting process ,timely reviewing or holding ethics meetings on scheme modification , informed consent modification ,serious adverse events ,etc.,clarifying the working process and time of ethical review ,and establishing unified and standardized review standards and approval standards.
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OBJECTIVE:To rapidly evaluate the effectiveness,safety and economics of rosuvastatin (RSV)in the treatment of dyslipidemia,so as to provide evidence-based support for clinical drug use. METHODS :Retrieved from PubMed ,Embase, Cochrane Library ,CNKI,Wanfang database and CBM ,etc.,health technology assessment (HTA)related website and database were searched systematically to select HTA report ,Meta-analysis/systemic evaluation and pharmacoeconomics study about RSV versus placebo or other positive drugs in the treatment of dyslipidemia. According to the inclusion and exclusion criteria ,two researchers independently screened the literatures ,extracted and summarized the data ,then performed qualitative description of results. RESULTS :Totally 11 Meta-analysis and 11 pharmacoeconomic studies were included ,and no relevant HTA report was retrieved. Results of the study showed that compared with the control group ,RSV could regulate dyslipidemia ,and reduce the levels of LDL-C ,TG,TC,C-reactive protein and sdLDL ;RSV could also reverse atherosclerotic plaque ,reduce all-cause mortality with good safety. In terms of economy ,compared with other statins or placebo ,RSV could prolong quality-adjusted life year,its incremental cost-effectiveness ratio is lower than the desired payment threshold ,which had more economic advantages. CONCLUSIONS:RSV is effective ,safe and economical in the treatment of hyperlipidemia.
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INTRODUCTION@#This study aims to examine the factors associated with self-reported hearing disability and early reduction in disability after first-time hearing aid (HA) fitting in Singapore.@*METHODS@#Retrospective record review of 1,068 subjects issued with HAs at a tertiary hospital from 2001 to 2013.@*RESULTS@#Subjects reporting ≥5 disabilities reduced from 90% to 24% after HA fitting. 'Difficulty hearing in noise' was the commonest disability before and after HA fitting, while 'needs to increase volume of TV/radio' was the disability with most improvement after fitting. In multivariable models, having worse pure tone audiometry (PTA) thresholds of the better hearing ear and being ethnically Chinese were associated with subjects reporting more hearing disabilities. A higher proportion of subjects reported a reduction rather than an absence of disability after HA fitting. In multivariable models, daily HA usage for ≥4 hours, sensorineural hearing loss (HL) and worse PTA thresholds of the better hearing ear were associated with reduction in more disabilities after HA fitting.@*CONCLUSION@#Hearing disability is high among first-time HA users in Singapore. Ethnicity and PTA thresholds were associated with self-reported hearing disability. After HA fitting, higher daily HA usage, sensorineural HL, and worse PTA thresholds of the better hearing ear were associated with early reduction in disability. Patient counselling on the benefits of HL rehabilitation could focus on hearing disability rather than PTA thresholds. The management of patients' expectations could focus on reducing rather than eliminating disability.
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The complement system is an important part of the innate immune system. More evidence showed that the function of complement was not only limited to the elimination of pathogens and other risk factors from the body but also affected the immune escape mechanism of the tumor through different activating pathways. Because of the complex and important role of complement in the tumor, this review expounds the mechanism of complement system participating in immune escape of the tumor from three aspects: complement inherent components, complement activation products and complement regulatory proteins. Additionally, these mechanisms are expected to provide a new application of complement in tumor immunotherapy with immune checkpoint inhibitors.
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The complement system is an important part of the innate immune system. More evidence showed that the function of complement was not only limited to the elimination of pathogens and other risk factors from the body but also affected the immune escape mechanism of the tumor through different activating pathways. Because of the complex and important role of complement in the tumor, this review expounds the mechanism of complement system participating in immune escape of the tumor from three aspects:complement inherent components, complement activation products and complement regulatory proteins. Additionally, these mechanisms are expected to provide a new application of complement in tumor immunotherapy with immune checkpoint inhibitors.
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Objective@#To explore the hot issues and developing trend of the research of campus bulling,and to provide a reference for the research on campus bullying.@*Methods@#The power of research, high-impact authors, highly cited journals, high-frequency keywords, and burst terms related to school bullying from the Web of Science database were analyzed using CiteSpace software. The data collection time was May 9, 2018.@*Results@#A total of 3 561 literature data were obtained. The results showed that the country with the highest number of publications was the United States; England had the highest centrality and was in a critical position in the research. The University of Turku in Finland was the core research institution. Salmivalli C was the author of the highest publication, Olweus D was the most frequent cited author. The high-impact journal was Aggressive Behavior. In terms of high-frequency keywords, the core vocabulary such as bully, adolescence, and victim were listed. Middle school students were the most frequently studied; in the form of bullying, the frequency of violence, aggression, and cyberbully was more common; depression, mental health and health appeared more frequently in terms of bullying outcomes. Mutant words including school children, bullying, victimization, relational aggression were more common.@*Conclusion@#The research hotspots on campus bullying during the past decade include violence, gender, social support, and mental health. Bullying among college students will be a hot research topic in the future. Continued efforts should be carried out in the field of campus bullying in China.
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Objective To analyze the dosimetric effect of inconsistent bladder filling states between the CT simulation and treatment for prostate cancer patients undergoing intensity-modulated radiotherapy (IMRT).Methods A total of 42 prostate cancer patients treated with IMRT were selected.After vacuum pad immobilization and simulation CT scan,the delineation of targets and organs-at-risk (OARs),treatment planning and dose calculation were performed on treatment planning system (TPS).The cone-beam-CT (CBCT) acquired before the first treatment was registered to planning CT,on which the target contours were duplicated and OARs were delineated.After dose recalculation on the CBCT using the same plan,the dosimetric differences on the CT and CBCT were compared,including mean dose of the planning target volume (PTV),homogeneity index (HI),conformity index (CI);the mean dose,V30,V40,V50,V60,and V65 of bladder and rectum respectively.Results Relative to the bladder volumes at simulation,the patients were divided into two groups with larger (15 cases) or smaller (27 cases) bladders at the first treatment.Comparing the parameters obtained from simulation CT with that from CBCT,the differences of the following parameters were of statistical significance:the bladder volume,PTV HI,PTV CI in both groups (t =6.838,-4.372,-3.553,-3.462,6.380,5.037,P< 0.05),the bladder V30,V40,V50,V60,V65(t=-5.004,-4.092,-3.124,-2.707,-2.489,P <0.05) and rectal V40,V50,V60,V65,mean dose in the group with smaller bladders (t=-2.946,-2.643,-2.426,-3.127,-2.530,P < 0.05),and the bladder V30,V40,V50 and mean dose in group with larger bladders (t =5.107,4.204,3.777,4.155,P<0.05).Conclusions For prostate cancer patients undergoing IMRT,the inconsistent bladder filling states between the planning and treatment will cause disimetric differences of targets and OARs.