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Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.
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Brucellosis is a kind of animal epidemic disease that can be transmitted to human beings through skin, mucous membrane, digestive tract, respiratory tract and other ways. In recent years, the incidence of brucellosis has increased. Its pathogenesis is relatively complicated. In addition to bacteria, toxins and other factors, genetic susceptibility has gradually attracted the attention of scholars. In this paper, we summarized the previous reports and reviewed the relationship between interleukin gene polymorphism and susceptibility to brucellosis.
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Objective:To compare the dose distribution among CyberKnife, Tomotherapy, Edge, Triology and γ-knife in stereotactic body radiation therapy (SBRT) for pancreatic cancer.Methods:Clinical data of 10 panreatic cancer patients receiving CyberKinife treatment were retrospectively analyzed. The treatment plans were designed by five apparatuses from five centers according to the uniform requirement. All plans were transferred to MIM system for the extraction of parameters, which mainly included D min, D mean and D max of PTV, conformity index (CI), new conformity index (nCI), homogeneity index (HI), gradient index (GI), coverage, D max and dose-volume of the stomach and bowel. Results:The best CI and nCI were obtained in Triology ( P<0.001), and the worst HI was found in γ-knife ( P<0.001). The best GI was found in CyberKnife, followed by γ-knife and Tomotherapy, and Edge showed the worst GI ( P<0.001). The highest D min of PTV was found in both Edge and Triology, while lower D min of PTV was found in CyberKnife and Tomotherapy ( P<0.001). Additionally, γ-knife provided the highest D mean and D max of PTV ( P<0.001). Regarding the organs at risk, the lowest D max and D 5cm 3 of the bowel ( P<0.001), D max of the stomach ( P=0.003), D max( P=0.001), D 5cm 3 ( P<0.001) and D 10cm 3 ( P=0.005) of the duodenum, D max( P<0.001) and D 0.35cm 3 ( P<0.001) of the spinal cord were found in CyberKnife. The highest D max of the bowel was found in γ-knife. Furthermore, the highest D 5cm 3 of the duodenum was demonstrated in Edge ( P<0.001) and Tomotherapy provided the highest D max( P<0.001) and D 0.35cm 3 of the spinal cord ( P<0.001). Conclusions:All five radiotherapy apparatuses can meet the requirement of SBRT for pancreatic cancer. More rapid dose fall-off could be obtained via CyberKnife and γ-knife. Triology and Edge provide better target conformity. CyberKnife can better protect the gastrointestinal tract.
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Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.
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P450 fatty acid decarboxylase OleT from Staphylococcus aureus (OleTsA) is a novel cytochrome P450 enzyme that catalyzes the oxidative decarboxylation of fatty acids to yield primarily terminal alkenes and CO2 or minor α-and β-hydroxylated fatty acids as side-products.In this work,the interactions between a series of cycloalkyl phosphorus heterocycles (CPHs) and OleTsA were investigated in detail by fluores-cence titration experiment,ultraviolet-visible (UV-vis) and 31p NMR spectroscopies.Fluorescence titration experiment results clearly showed that a dynamic quenching occurred when CPH-6,a repre-sentative CPHs,interacted with OleTsA with a binding constant value of 15.2 × 104 M-1 at 293 K.The thermodynamic parameters (△H,△S and △G) showed that the hydrogen bond and van der Waals force played major roles in the interaction between OleTsA and CPHs.The UV-vis and 31p NMR studies indicated the penetration of CPH-6 into the interior environment of OleTsA,which greatly affects the enzymatic activity of OleTsA.Therefore,our study revealed an effective way to use phosphorus hetero-cyclic compounds to modulate the activity of cvtochrome P450 enzymes.
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Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.
Subject(s)
Animals , Rats , Aconitine/pharmacology , Analgesics/pharmacology , Pharmaceutical Preparations , Rats, Sprague-DawleyABSTRACT
Brucellosis is an zoonosis, humans can be infected by Brucella through skin, mucous membrane, digestive tract, respiratory tract and so on. In the past, most of them recorded the infection of brucellosis from animal to human, but rarely reported the transmission of brucellosis between humans. This paper retrospectively reviews previous reports describing the spread of brucellosis between humans.
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Objective:To construct a standardized training course system for new nurses in radiology department based on their post competency.Methods:The first draft of standardized training course for new nurses in radiology department was drawn up by referring to domestic and foreign literature, expert interview and group discussion. 20 experts in radiology department from 12 third grade hospitals were consulted for two rounds by Delphi method, and the index weight at all levels was determined by AHP.Results:The standardized training course system of new nurses in radiology department based on post competency includes four first level indicators (knowledge, skills, situational decision-making, humanistic quality), 10 second level indicators and 55 third level indicators. In the second round of expert consultation, the positive coefficient of experts was 85%, 100% and the authoritative coefficient was 0.75 and 0.80 respectively; In the second round expert consultation, the harmony coefficient of the first, second and third level indexes was 0.401 and 0.493 respectively, P < 0.01. Conclusion:the standardized training course system of new nurses in radiology department based on post competency is scientific and reasonable, which can provide reference for standardized training of new nurses in radiology department.
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Brucellosis is a zoonotic disease caused by Brucella,and osteoarthritis can be caused when the bone and joint system is involved.In this paper,epidemiology,pathogenesis,clinical manifestation and diagnosis of brucellosis are discussed in detail.At the same time,a better understanding of the clinical characteristics of brucellosis helps clinicians in better diagnosis and treatment of brucellosis.
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Brucellosis is a zoonosis caused by Brucella infection, through digestive tract, respiratory tract and damaged skin or mucous membrane infection, and in recent years its incidence is on the rise. Based on the literature published in recent years, this article summarized the treatment of acute and chronic period brucellosis, brucellosis complications, brucellosis in children, brucellosis during pregnancy, brucellosis with liver and kidney injury and immunosuppressant treatment.
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Objective To present the distinction on clinical features,laboratory features,treatment schemes between the patients with and without brucellar epididymo-orchitis,and to provide a theoretical basis for clinical diagnosis and treatment.Methods A retrospective analysis of 223 male patients with brucellosis in the First Hospital of Jilin University from June 2010 to November 2016 was carried out.A comparative analysis of the clinical and laboratory features of 22 patients with epididymo-orchitis and 201 cases without epididymo-orchitis was done.The SPSS 23.0 software was used to analyze the statistical results,P ＜ 0.05 was defined as statistically significant.Results Epididymo-orchitis occurred in 9.87％ (22/223) of all male patients with brucellosis.The median ages of patients with and without epididymo-orchitis were 35.5 and 42.0 years old,respectively,the difference was not statistically significant (Z =1.323,P ＞ 0.05).Cases with and without epididymo-orchitis of brucellosis with fever [90.9％ (20/22) vs 69.2％ (139/201)],chills [54.4％ (12/22) vs 28.9％ (58/201)],hepatomegaly [22.7％ (5/22) vs 3.5％ (7/201)],abdominal symptoms [59.1％ (13/22) vs 17.4％ (35/201)],and urinary tract infection symptoms [31.8％ (7/22) vs 3.5％ (7/201)],the differences were statistically significant (x2 =4.586,6.076,14.424,20.392,27.059,all P ＜ 0.05).The medians of white blood cell (WBC) count (7.9 × 109/L),erythrocyte sedimentation value (ESR,38.0 mm/h),and aspartate aminotransferase (AST,110.0 U/L) in brucellosis with epididymo-orchitis were higher than those without epididymo-orchitis (5.1 × 109/L, 30.0 mm/h,73.8 U/L),the differences were statistically significant (Z =2.239,2.064,2.762,all P ＜ 0.05).All brucellosis patients with epididymis-orchitis were treated with antibiotics for 8 weeks.The defervescence time was 4.5 days,the time of pain relief was 3.9 days,21 patients were cured,and only Ⅰ patient relapsed.Conclusions Epididymo-orchitis is a common complication of brucellosis.Brucellar epididymo-orchitis is usually characterized with a severe acute clinical presentation,which needs timely diagnosis.Combination of antibiotics treatment for 8 weeks in brucellosis patients with epididymis-orchitis is effective.
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Objective To evaluate the value of superb micro-vascular imaging(SMI) in the detection of TI-RADS 4 thyroid nodules . Methods A retrospective analysis of 61 patients( 68 thyroid nodules) with grade 4 TI-RADS diagnosed by routine ultrasound and undergone SMI were performed ,and the differences between CDFI and SMI were compared . The TI-RADS level were corrected by CDFI and SMI technology , combined with the pathological results to compare the diagnostic efficacy before and after the correction . At the same time ,the related factors had been collected to evaluate the risk factors and to compare the value of SMI in benign and malignant nodules . Results SMI was more likely to detect the type Ⅲ blood flow ( P =0 .001) of malignant nodules . The area under the ROC curve before TI-RADS correction ,after CDFI correction and SMI correction were 0 .66 ,0 .69 and 0 .78 ,respectively . Compared with before TI-RADS correction and after CDFI correction ,the area under the curve of SMI correction was significant different ( P=0 .002 ,0 .009) . There was no significant difference in the area under the curve between after CDFI correction and before correction ( P = 0 .4196 ) . The sensitivity of SMI was higher ,but there was no significant difference ( P >0 .05) . After single factor analysis and multivariate analysis ,central blood flow and perforating blood flow found by SMI were not independent risk factors for thyroid cancer . Conclusions SMI is more effective than CDFI in detecting TI-RADS 4 thyroid nodules ,and it is expected to be an auxiliary tool for the diagnosis of benign and malignant thyroid nodules .
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Objective To evaluate the performance of a customized vacuum-form body immobilization method in the radiotherapy of pelvic malignancies by comparing it with conventional approaches, thus to improve immobilization accuracy in the radiotherapy of pelvic malignancies. Methods A total of 66 patients with pelvic malignancies were enrolled in this study. These patients were divided into three groups according to three immobilization approaches: radiotherapy board ( Group N ) , conventional vacuum cushion ( Group V ) , and a customized vacuum cushion specifically for pelvic immobilization ( Group New-V) . Setup deviations of these immobilizations were comparatively evaluated by translational and rotational errors during intra-fractional measurements. Results The average translational setup errors in vertical(x), longitudinal(y), lateral(z) and rotational error r were (0. 35 ± 0. 37), (0. 21 ± 0. 22), (0. 29 ± 0. 28) cm and (0. 70 ± 0. 65)° for Group New-V; (0. 44 ± 0. 43), (0. 31 ± 0. 62), (0. 45 ± 0. 60) cm and (1. 25 ± 1. 00)° for Group N; (0. 38 ± 0. 36), (0. 27 ± 0. 25), (0. 32 ± 0. 29) cm and (1. 09 ± 0. 77)° for Group V, respectively. Significant differences were observed in r direction among these three method (F=7. 859,P <0. 05). Group New-V with customized cushion showed the least standard deviations in four directions and the least setup error in r direction compared with the other two method (F=3. 166,P<0. 05). Reconstructed dose distribution based on the isocenter shift result ed from setup errors revealed that Group New-V showed the least deviations in the minimum and mean dose and of the planning target volume (PTV) before and after isocenter shift(F=8. 018, P<0. 05). Conclusions The customized vacuum cushion provided best immobilization and dosimetric advantage. It helps to optimize the immobilization accuracy and improve the clinic outcome potentially.
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Objective To analyze the clinical and laboratory results and epidemiological characteristics of brucellosis.Methods The clinical and laboratory characteristics brucellosis cases (confirmed by Brucellosis Guidelines 2012) at the Department of Infectious Disease of the First Hospital of Jilin University between 2000 and 2016,were retrospectively evaluated.The patients were divided into two groups according to acute and chronic stages.According to the range of lesions,the lesions were divided into two groups,and comparative analysis of data between groups was done.Results The ages of the 607 patients (489 males,118 females) were ranged from 2 to 80 years.Among the 607 patients,570 (93.9％) were diagnosed with acute brucellosis,37 (6.1％) with chronic brucellosis.Focal involvement was found in 418 (68.9％) patients.Among them,382 patients were in acute stage,and the other in chronic phase (36).Acute patients' alanine aminotransferase (ALT) and aspartate transaminase (AST) were higher than those of chronic brucellosis (U/L:47.2 vs 26.7,44.5 vs 24.0,Z =-3.684,-3.754,all P ＜ 0.05).Although the white blood cell count,platelet values,C-reactive protein,and blood sedimentation were higher in patients with focal involvement (x 103/mm3:7.3 vs 5.4,211 vs 176;mg/L:56.0 vs 30.5;mm/h:37 vs 28,Z =-4.407,-2.709,-2.334,-2.137,all P ＜ 0.05),patients without focal involvement had higher ALT and AST (U/L:33.3 vs 53.9,30.2 vs 48.1,Z =-4.102,-3.730,all P ＜ 0.05).Peripheral arthritis was the most common type of osteoarticular involvement in 317 patients with focal involvement,and peripheral arthritis was found to be the most frequently identified in the knee joint,112 patients (35.3％).Totally 80 patients were followed up,the relapse rate was 20.0％ (16/80),2 patients treatment failure,only 1 patient died after 1 month of treatment who was diagnosed neuropathic brucellosis.Conclusions Focal involvement should be investigated in the presence of leucocytosis,and pain of a certain part.
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Objective To study the effect of qiangguixishu pills in the treatment with knee osteoarthritis and influence in miR of circulating and inflammatory factor index.Methods 50 patients with KOA from October 2014 to October 2015 were randomly divided into two groups,the observation group and the control group,with 25 cases in each group.The control group using Diacerein capsules for treatment,the observation group received the Qiangguixishu pills for treatment,compared the WOMAC score and clinical efficacy before and after treatment between two groups,and changes of miR and inflammatory factors circulating.Results There was no difference in WOMAC score between the two groups before treatment;pain,joint stiffness, daily activities and comprehensive scores were decreased after treatment in two groups(P<0.05),and it was lower in the observation group than in the control group(P<0.05);There was no significant difference at blood miR-146a,miR-140,miR-21,IL-6,IL-1beta,TNF-alpha contents between the two groups,miR-21 beta,IL-6,IL-1 beta,TNF-alpha were lower than that before treatment in the two groups after treatment(P<0.05),miR-140,miR-146a were higher than before treatment(P<0.05),and compared with the control group,the above indicators at the observation group were had significant difference(P<0.05).Conclusion There were the therapeutic effect in the treatment with KOA by Qiangguixishu pills and its mechanism maybe realized by regulating the miR and inflammatory factor.
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Objective To study the sensitivity and reliability of rat skin anaphylactoid test method, detect and evaluate the anaphylactoid reaction of traditional Chinese medecine injection. Methods The condition of rat skin anaphylactoid test was optimized by studying the influencing factors of sensitivity and reliability of test with C48/80 as a tool drug, Tween80, endotoxin, China cobra toxin, trichosanthin injection, Tanreqing injection and Xuesaitong injection were investigated. Results The best conditions of rat skin anaphylactoid test was as follows:intrademal inject the drug with insulin syringe, 50-100μL per point, immediately inject 0.5%Evans blue dye 1 mL though caudal vein, 15 min later, kill the rat by carotid artery bleeding, clip dorsal skin to do the test. With this method, Tween80, endotoxin, China cobra toxin and trichosanthin injection all can induce blue stain in rat skin. Tanreqing injection showed no blue stain at the clinical dose. Xuesaitong injection although can induce blue stain in rat skin at the clinical dose, but the results cannot exclude the interference of its pharmacological function. Conclusion The method is simple with short test cycle, less dose of test drug, high detection sensitivity and good reproducibility, but some drug can show false positive result due to its own property.
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Computer tomography scanning was performed in 16 patients with mandibular angle hypertrophy before and after surgery. The imaging data of patients were recorded in three-dimensional reconstruction software (Mimics 10.0), and found the most appropriate surgery plan through simulating different surgical procedures. The geometry character indexes of the face were compared between before and after surgery, and then the results were analyzed. We got intuitive, accurate three-dimensional reconstruction graphs, simulation of surgery procedures, and calculation of difference in the geometry character index of face in all cases. The bone width of mandibular angle shortened (7.69?.89) mm; the soft tissue width of mandibular angle shortened (5.13?.19) mm; the both gonial angle increased (5.68?.43)?and (5.91?.66)? respectively. Applied to actual surgery procedure,the operation time shortened and precision of operation was improved. Results demonstrated that Computer three-dimensional reconstruction and computer simulation techniques is beneficial to reveal the variational regularity of bone and soft tissue, which is a good aided method in stimulation of surgery and choice of surgery plan.
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Objective To realize foot switch long-distance control of PC for medical image acquisition. Methods The foot switch was connected with PC through RS232 DB9 port, and the software was programmed by Microsoft Visual C++6.0 on Windows 2000 operating system. Results Foot switch control of PC was successfully achieved in acquiring medical images. Conclusion The foot switch has the advantages of long-distance and foot control of PC. It not only saves manpower but ensures the accuracy and real time of images acquired. This method can be applied to image acquisition workstations for medical equipments such as CT apparatus, X-ray apparatus, Ultrasound apparatus, Endoscope apparatus and so on.
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Reproductive health is a focus of the 21st century medical sciences. Researches on the correlation between psychological factors and male reproductive health may help discover the rules of the development of male diseases. This paper analyzes the social root-cause of the adverse psychological factors of men, discusses how psychological factors affect male reproductive health, and proposes some remedial measures for related psychological problems.
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Humans , Male , Penile Erection , Psychology , Psychology, Social , Reproductive Medicine , Sex Education , Stress, PsychologicalABSTRACT
Objective The images of CT Equipment without DICOM interface are stored by means of film all along,and they can't be digitally stored,shared,retrieved,integrated to diagnostic reports.This paper introduces a method to capture images,mainly focus on the image capture and crop technology.Methods The hardware is composed of Philip Tomoscan AV CT,PC,OK_RGB20B image capture card,foot switch.The software is programmed by Microsoft Visual C++6.0,OK_RGB20B SDK and GDI+ Class Library on Windows 2000 operating system.Results The system can capture the CT image successfully,and make the images stored and shared permanently.Conclusion This method is a valuable clew for capturing images from other types of non-DICOM-based medical equipment such as ECT,X-ray,Ultrasound,Endoscope and so on.