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Objective:To investigate the necessity and feasibility of the virtual simulation teaching experiment software of the bronchoscopy intelligent navigation-based fiducial marker implantation technology in the clinical application of radiotherapy.Methods:This study developed a 3D virtual operation and interactive system using the Unity3D engine, tools including 3Dmax and Maya, and the SQL database. The scenes in the system were produced using the currently popular next-generation production process. Targeting the priorities and difficulties in the implantation of fiducial markers, the system developed in this study allowed for simulated demonstration and training based on 12 steps and 10 knowledge points. Internal tests and remote evaluation tests were adopted in this system to obtain the test result of each subject. Then, the application value of the system was analyzed based on the test result.Results:As of May 1, 2022, the system had received 2 409 views and 425 test participants, with an test completion rate of 100% and an experiment pass rate of 96.5%. Moreover, this system won unanimous praise from 167 users, primarily including the students majoring in multilevel medical imaging technology and medical imaging science from the Fujian Medical University, as well as the radiotherapy-related staff of this university.Conclusions:The virtual simulation teaching experiment software of the bronchoscopy intelligent navigation-based fiducial marker implantation technology can be applied to the teaching of students and the training of related professionals.
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Objective:To improve the quality assurance (QA) skills of radiotherapy personnel and medical students and reduce the radiation risk of training by developing a remote training system for QA of medical electronic linear accelerators.Methods:This training system was built based on radiotherapy technology and quality control contents of medical electronic linear accelerators, and a virtual reality interactive software was developed using extended reality (XR) technology Unity 3D. A remote control module of multi-terminal platform was also developed. A multi-perspective evaluation system was adopted and a questionnaire was designed to analyze the application value of this system.Results:The training system reproduced the live environment and physical objects of medical electronic linear accelerator treatment room. It built a multi-terminal virtual simulation training system with radiotherapy technology as well as QA knowledge system. This system could provide 5G remote control of medical electronic linear accelerator for off-site quality control demonstration and guidance. By March 1, 2022, a total number of 133 people had been trained using this system, 76 valid questionnaires had been taken, of which 90.79% (69/76) of the respondents trusted the experimental results shown by the system and 88.16% (67/76) of the respondents considered the training system necessary.Conclusions:The training effect of this system is widely recognized. It fundamentally reduces the training radiation hazard and provides reference for the reform and progress of QA training mode of medical electronic linear accelerators.
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OBJECTIVE@#This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.@*METHODS@#We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.@*RESULTS@#The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.@*CONCLUSION@#Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Subject(s)
Humans , beta-Thalassemia/genetics , alpha-Thalassemia/genetics , Hemoglobinopathies/genetics , China/epidemiology , High-Throughput Nucleotide SequencingABSTRACT
Objective:To explore the feasibility of recoverable fiducial marker implantation guided using the intelligent navigation bronchoscopy technology in the Cyberknife Synchrony-based respiratory tracking.Methods:CT scans of an inflatable pig lung after anti-rot processing were obtained. Then, eight simulated tumor lesion sites were designed in the left and right lung lobes using intelligent navigation software, with four classified as the sputum bronchial environment group and four classified as the wet bronchial environment group. Based on the implantation principle of Cyberknife fiducial markers, 32 recoverable fiducial markers were implanted around various simulated tumor lesions via bronchus under intelligent guidance. Then, the end-expiratory state of the pig lung was simulated, the pig lung was scanned again to obtain CT images of the implanted recoverable fiducial markers, and the number of successfully implanted fiducial markers was recorded. Eight deliverable Synchrony treatment protocols were designed using the Cyberknife planning system (Multiplan v4.6), and then the pig lung with simulated respiratory movements was exposed to radiation. After radiation, the implanted recoverable fiducial markers were retrieved using the bronchoscopy technique, and the number of successfully retrieved fiducial markers was recorded. Moreover, the translational errors, rotational errors, and rigid body errors were extracted from the Cyberknife log file and analyzed.Results:No recoverable fiducial markers slipped or fell during the experiment. Thirty-two recoverable fiducial markers were successfully implanted and recovered under the guidance of intelligent navigation bronchoscopy, with implantation and recovery success rates of both 100%. Moreover, the tracking rate and rigid body errors of the fiducial markers were 100% and less than 5 mm, respectively. The data from the Cyberknife log file indicated that there was no significant difference between the sputum bronchial environment group and the wet bronchial environment group in the translational errors in the left-right direction, the rotational errors in the roll direction, and the rotational errors in the pitch direction ( P>0.05). Compared to the wet bronchial environment group, the sputum bronchial environment group had slightly higher translational errors in front-back ( Z=-3.57, P<0.01) and cranio-caudal ( Z=-2.53, P<0.05) directions, lower rotational errors along the yaw axis ( Z = -3.88, P < 0.01), and lower rigid body error ( Z=-3.32, P<0.01), and the differences were all statistically significant. Conclusions:The recoverable fiducial marker implantation guided using the intelligent navigation bronchoscopy technology is feasible. Recoverable fiducial markers are stable in the bronchus of the phantom, and the Cyberknife tracking precision can meet clinical requirements. Therefore, the recoverable fiducial marker implantation guided using the intelligent navigation bronchoscopy technology has promising prospects in clinical and teaching applications.
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Objective: The moisture content in the soil directly affects the yield and quality of Panax notoginseng, especially at the age of three years old. However, the suitable moisture for the growth of P. notoginseng is unknown. In this study, the effects of different soil moisture on the growth of P. notoginseng were studied. Methods: Four different water treatments (0.45 field capacity (FC), 0.60 FC, 0.70 FC, and 0.85 FC) were set up in Shilin County, Yunnan Province, China. The water consumption and daily dynamic of water consumption were determined daily (from April 21 to October 18, 2012), and the daily dynamic of water consumption under different weather conditions (sunny and rainy) was determined. The transpiration coefficient and water use efficiency were calculated through dry matter accumulation and total water consumption. Accumulation of saponins of roots of P. notoginseng were analyzed by HPLC after treated, and the soil moisture content suitable for the growth of P. notoginseng was estimated by regression fitting of the active ingredient accumulation and the soil moisture content. Results: The water consumption of 0.85 FC, 0.70 FC, 0.60 FC and 0.45 FC were 2.89, 3.68, 3.37 and 2.73 kg/plant per day, respectively. The water consumption of P. notoginseng from June to August was greater than other months. The daily dynamic of water consumption on sunny days and sunny days after rain showed a “double peak” feature, and it showed a “single peak” feature on rainy days. The water uses efficiency (WUE) of 0.85 FC, 0.70 FC, 0.60 FC and 0.45 FC were 2.51, 3.32, 4.59, 3.39 gDW/kg H
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Objective: To investigate the independent risk factors of cardiorenal syndrome type 1 (CRS1) in patients with acute myocardial infarction (AMI) and to build a predictive equation for the development of CRS1 in these patients. Method: Consecutive inpatients with AMI, who hospitalized from January 2017 to December 2018 in the Hunan Provincial People's Hospital, were enrolled in this case-control study. Patients were divided into CRS1 group and non-CRS1 group according to the presence or absence of CRS1.The clinical data were collected through the electronic medical record system of Hunan Provincial People's Hospital. The matching process was conducted with a minimum-distance scoring method and a 1∶1 match between the CRS1 group and the no-CRS1 group, the propensity score was calculated through the logistic regression model. Factors with statistically significant differences in univariate analysis were included in the multivariate logistic regression model to analyze the risk factors of AMI patients with CRS1, then the independent risk factors were used to establish a predicting equation for CRS1 by logistic regression function for model building. Area under the curve (AUC) value and the best cut-off value of the combined predictors was determined according to the ROC curve. Python 3.8 software was used to perform 10-fold cross-validation on modeling samples. Results: A total of 942 patients were included, there were 113 cases in CRS1 group and 829 cases in non-CRS1 group. Ultimately, 99 CRS1 patients were successfully matched to 99 non-CRS1 patient using 1∶1 matching. After propensity score matching, the baseline age and sex along with heart rate, mean arterial pressure, percentage of people with a history of diabetes, hypertension, ST-segment elevation myocardial infarction, myocardial ischemia time, angiotensin converting enzyme inhibitors or angiotensin Ⅱ receptor blockers use, and β receptor blocker use were similar between the two groups(all P>0.05). The contrast agent dosage was also similar between the two groups (P=0.266). The peak cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide(NT-proBNP), white blood cell count, base estimated glomerular filtration rate (eGFR), albumin and hemoglobin levels were statistically significant between the two groups (all P<0.05). Multivariate logistic regression analysis showed that decreased baseline eGFR, increased NT-proBNP, peak cTnI concentrations and white blood cell count were independent risk factors of CRS1 in AMI patients (all P<0.01).The predicting equation of the combined predictor was established by transforming the logistic model equation, L=0.031×cTnI+0.000 2×NT-proBNP-0.024×eGFR+0.254×white blood cell count, where L represented the combined predictor. ROC curve analysis indicated that the AUC of the peak cTnI, NT-proBNP, baseline eGFR, white blood cell count, and combined predictor were 0.76, 0.85, 0.79, 0.81, and 0.92 respectively (all P<0.05), and the cutoff value of combined predictor was 2.6. The AUC of ROC curve after the model's ten-fold cross validation was 0.89. Conclusions: Decreased baseline eGFR, increased NT-proBNP, peak cTnI concentrations and white blood cell count are the independent risk factors for CRS1 in AMI patients. The combined predictor equation based on the above 4 biomarkers presents a good predictive value for CRS1 in AMI patients.
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Chemical stimulation of the kidney increases sympathetic activity and blood pressure in rats. The hypothalamic paraventricular nucleus (PVN) is important in mediating the excitatory renal reflex (ERR). In this study, we examined the role of molecular signaling in the PVN in mediating the capsaicin-induced ERR and sympathetic activation. Bilateral PVN microinjections were performed in rats under anesthesia. The ERR was elicited by infusion of capsaicin into the cortico-medullary border of the right kidney. The reflex was evaluated as the capsaicin-induced changes in left renal sympathetic nerve activity and mean arterial pressure. Blockade of angiotensin type 1 receptors with losartan or inhibition of angiotensin-converting enzyme with captopril in the PVN abolished the capsaicin-induced ERR. Renal infusion of capsaicin significantly increased NAD(P)H oxidase activity and superoxide anion production in the PVN, which were prevented by ipsilateral renal denervation or microinjection of losartan into the PVN. Furthermore, either scavenging of superoxide anions or inhibition of NAD(P)H oxidase in the PVN abolished the capsaicin-induced ERR. We conclude that the ERR induced by renal infusion of capsaicin is mediated by angiotensin type 1 receptor-related NAD(P)H oxidase activation and superoxide anion production within the PVN.
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Objective:To develop a remote training system for CT simulation positioning of radiotherapy using virtual reality technology, and to explore a new method of medical training.Methods:The 3DMax and Maya were employed to establish the 3D model. The unity3D engine was adopted to develop 3D virtual operation and interaction system. Java spring MVC architecture was utilized as the system background service. MySQL was used as the background database system. The users were assigned into two roles: teacher and student, and the modes were divided into teaching and assessment modes.Results:The function of the system covered the whole process of CT simulation positioning, mainly including modules of patient information management, CT simulation positioning machine cognition, body position fixation technology, CT positioning scanning, and emergency handling, etc. Since it was put into use in 2018, the system has been running stably, with 14 920 pages views and an 86.66% pass rate. Compared with the traditional training, the training efficiency has been significantly improved and has received unanimous recognition.Conclusions:The remote training system can effectively improve the clinical practice ability and humanistic care ability of the trainees, which has good autonomy, sharing, and innovation. At present, the system has been put online and has strong popularization with prospects for broad application.
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OBJECTIVE@#To analyze the genotype and phenotype of a sibpair with partial deletion of SATB2 gene caused by 2q33.1 microdeletion.@*METHODS@#Both children have featured mental retardation and development delay, and were subjected to karyotyping, single nucleotide microarray (SNP array) and real-time fluorescence quantitative PCR analysis. Karyotyping and SNP Array analysis were also carried out on their parents to verify the origin of mutation.@*RESULTS@#Both sibs had a normal karyotype. SNP array showed that sib 1 had arr[hg19]2q33.1(200 192 328 - 200 197 269)×1 (4.9 kb), 2q35 (218 105 663 - 218 816 675)×3 (711 kb), while sib 2 had arr[hg19]2q33.1(200 192 328 - 200 197 269)×1 (4.9 kb), 2q35 (218 105 663-218 810 908)×3 (705.2 kb). The deletion has partially overlapped with that of 2q33.1 microdeletion syndrome and involved part of the SATB2 gene. The result of real-time fluorescence quantitative PCR assay was consistent with that of SNP assay. The duplication has originated from their father and has not been associated with any disease phenotypen.@*CONCLUSION@#Both sibs have carried partial deletion of SATB2 gene and had similar clinical phenotypes. Haploinsufficiency of such gene probably underlies the clinical manifestations in both patients.
Subject(s)
Child , Humans , Chromosome Deletion , Chromosome Disorders , Chromosomes, Human, Pair 2 , Genetic Testing , Karyotyping , Matrix Attachment Region Binding Proteins , Genetics , Phenotype , Transcription Factors , GeneticsABSTRACT
The pharmacological activity of active ingredients from Chinese medicine depends greatly on the microecological environment of probiotics in the human body. After effective ingredients from traditional Chinese medicines are metabolized or biotransformed by probiotics, their metabolites can increase pharmacological activity, and can be absorbed more easily to improve the bioavailability. Therefore, the combination of Chinese medicines with probiotics is the innovation point in R&D of functional food and Chinese medicines, and also a new thinking for the modernization of Chinese medicine.This review summarizes and analyses the research progress on metabolism effects of gut microbiota on Chinese medicines components, the regulating effect of effective ingredients from Chinese medicine on intestinal probiotics, the application status of probiotics in traditional Chinese medicines, and the main problems and prospects in the research and development of Chinese medicines products with probiotic, aiming to provide theoretical guidance and practical value for the fermentation engineering of Chinese herbal medicine.
Subject(s)
Humans , Drugs, Chinese Herbal , Metabolism , Medicine, Chinese Traditional , ProbioticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the inhibitory effect of 420 nm intense pulsed light on Trichophyton rubrum growth in vitro and explore the mechanism.</p><p><b>METHODS</b>The fungal conidia were divided into treatment group with intense pulse light irradiation and control group without irradiation. The surface areas of the fungal colonies were photographed before irradiation and on the 2nd and 3rd days after irradiation to observe the changes in fungal growth. The viability of the fungus in suspension was detected at 6 h after irradiation using MTT assay. The intracellular reactive oxygen species (ROS) level in the fungus was determined using DCFH-DA fluorescent probe, and the MDA content was detected using TBA method.</p><p><b>RESULTS</b>Intense pulse light (420 nm) irradiation caused obvious injuries in Trichophyton rubrum with the optimal effective light dose of 12 J/cmin 12 pulses. At 6 h after the irradiation, the fungus in suspension showed a 30% reduction of viability (P<0.05), and the fungal colonies showed obvious growth arrest without further expansion. Compared to the control group, the irradiated fungus showed significant increases in ROS level and MDA content (P<0.05).</p><p><b>CONCLUSION</b>Intense pulse light (420 nm) irradiation can induce oxidative stress in Trichophyton rubrum to lead to fungal injuries and death.</p>
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BACKGROUND:Urtica,as a traditional Chinese medicine,is famous for anti-inflammatory,detumescence and anti-rheumatic effects,but its effect on osteoarthritis remains unknown.OBJECTIVE:To investigate the therapeutic effect of different concentrations of urtica on osteoarthritis and the underlying mechanism.METHODS:(1) Eighteen rats were selected,and after their hair was shaved,the rats were divided into three groups (n=6 per group).The rat skin was painted with paraffin,urtica colloid and 0.8％ formaldehyde,respectively,and the skin rash and swelling were observed.(2) Thirty rats were selected,and the rat model of osteoarthritis was established by injecting papain,followed by equally allotted into 100,200,and 400 mg/kg urtica and positive control groups.The diameter of the rat left knee was measured at 1,2 and 3 weeks after administration to determine the severity of knee swelling.The rat model of acute pain was established with 0.6％ acetic acid solution,and then the model rats were subjected to different concentrations of urtica or normal saline (control group).(3) The frequency of rat tumbling and twisting was observed to determine the analgesic effect of urtica.The levels of interleukin-1β,tumor necrosis factor-α and matrix metalloproteinase 3 in the synovial fluid of the left knee joint were detected by ELISA at 1,2 and 3 weeks after administration.RESULTS AND CONCLUSION:After urtica administration,no edema or rash appeared on the rat skin surface.Compared with the control group,200 and 400 mg/kg urtica could reduce joint swelling and pain,showing no significant difference from indomethacin.Compared with the control group,200 and 400 mg/kg urtica reduced the levels of interleukin-1 β,tumor necrosis factor-α and matrix metalloproteinase 3 in the synovial fluid.These results manifest that urtica exerts the effects of anti-inflammation,analgesia,detumescence and anti-osteoarthritis.
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Tumor necrosis factor-alpha (TNF-α) has been found to be centrally involved in the development of ischemia-reperfusion injury (IRI)-induced inflammation and apoptosis. Knockdown of TNF-α gene using small interfering RNA (siRNA) may protect renal IRI. Renal IRI was induced in mice by clamping the left renal pedicle for 25 or 35 min. TNF-α siRNA was administered intravenously to silence the expression of TNF-α. The therapeutic effects of siRNA were evaluated in terms of renal function, histological examination, and overall survival following lethal IRI. A single systemic injection of TNF-α siRNA resulted in significant knockdown of TNF-α expression in ischemia-reperfusion injured kidney. In comparison with control mice, levels of BUN and serum creatinine were significantly reduced in mice treated with siRNA. Pathological examination demonstrated that tissue damage caused by IRI was markedly reduced as a result of TNF-α siRNA treatment. Furthermore, survival experiments showed that nearly 90% of control mice died from lethal IRI, whereas more than 50% of siRNApretreated mice survived until the end of the eight-day observation period. We have demonstrated for the first time that silencing TNF-α by specific siRNA can significantly reduce renal IRI and protect mice against lethal kidney ischemia, highlighting the potential for siRNA-based clinical therapy.
Subject(s)
Animals , Humans , Mice , Apoptosis , Disease Models, Animal , Genetic Therapy , Inflammation , Genetics , Pathology , Therapeutics , Kidney , Wounds and Injuries , Pathology , RNA, Small Interfering , Genetics , Reperfusion Injury , Genetics , Pathology , Therapeutics , Tumor Necrosis Factor-alpha , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of NADPH oxidase (Nox) in the oxidative stress injury of human dermal fibroblasts (HFbs).</p><p><b>METHODS</b>An oxidative stress injury model was established in HFbs by exposure to H(2)O(2). Normal HFbs and HFbs exposed to H(2)O(2) with and without pretreatment with NADPH oxidase inhibitor were tested for cell viability using MTT assay, and the intracellular reactive oxygen species (ROS) were determined with a DCFH-DA fluorescent probe. Western blotting was used to measure the protein expressions of membrane-bound subunit gp91phox of NADPH oxidase in the cells.</p><p><b>RESULT</b>H(2)O(2) time- and concentration-dependently induced oxidative stress injury in the fibroblasts, causing a reduction of the cell viability to 40% after a 24-h exposure at 700 µmol/L (P<0.05) and an increase of ROS by 2 folds after a 2-h exposure at 700 µmol/L (P<0.05). Compared with the cells with oxidative stress injury, the cells with NADPH oxidase inhibitor pretreatment showed a 20% higher cell viability (P<0.05) and normal ROS level (P<0.05) following H(2)O(2) exposure. Western blotting demonstrated increased expression of gp91phox in the cells exposed to increasing H(2)O(2) concentrations, but gp91phox expression remained normal in cells pretreated with NADPH oxidase inhibitor.</p><p><b>CONCLUSION</b>H(2)O(2) can induce oxidative stress injury in the fibroblasts by affecting NADPH oxidase, especially its membrane-bound subunit gp91phox.</p>
Subject(s)
Humans , Cell Survival , Cells, Cultured , Fibroblasts , Cell Biology , Hydrogen Peroxide , Membrane Glycoproteins , Metabolism , NADPH Oxidase 2 , NADPH Oxidases , Metabolism , Oxidation-Reduction , Oxidative Stress , Reactive Oxygen Species , MetabolismABSTRACT
Objective To study the salt intake of patients undergoing maintenance hemodialysis and explore their knowledge and behaviour. Methods The patients undergoing maintenance hemodialysis were offered salt spoon and soy sauce cup. Their diaries on home meals for 3 consecutive days were collected to calculate their salt intake. Meanwhile, a one to one interview was done to evaluate the accuracy of patient′s diet diary and the knowledge and behavior of low salt diet and find out related factors of salt intake. Results The average salt intake was (6.49 ± 1.64)g/d. The average composition rate in the low salt diet knowledge in low salt diet behavior was 51.00% and 47.00% respectively. Age and education level were the influencing factors of salt intake. Conclusions The average salt intake is much higher than the standard for the patients undergoing maintenance hemodialysis. Their low salt diet knowledge is in the middle level and their low salt diet behavior is in the middle or lower level. The related factors include age and education among patients undergoing maintenance hemodialysis.
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The tail suspension test (TST), forced swimming test (FST) and chronic unpredictable mild stress (CUMS) model were used to evaluate the anti-depressant effect of supercritical CO2 extract from Compound Chaigui Fang (FFCGF). A nuclear magnetic resonance (NMR)-based metabonomics combined with multivariate statistical analysis was performed to explore the mechanism of FFCGF. Rats were conducted by CUMS procedure for 28 days and drugs were administrated at the same time. The body weight, sucrose preference, crossings and rearings in open-field tests were evaluated and the urine was collected simultaneously. The metabonomic profiles of rats' urine were analyzed by NMR and potential biomarkers were searched by multivariate statistical analysis. The results showed that administration of FFCGF significantly decreasing the immobility time in FST and TST and improving rats' body weight, sucrose preference, crossings and rearings in CUMS, which were indication that the anti-depressant effect of FFCGF was abvious. Significant differences in the metabolic profile of the CUMS treated group and the control group were observed, which were consistent with the results of behavioral tests. Decreased levels of acetic acid, succinic acid, 2-oxidation glutaric acid and citric acid and increased glycine and pyruvic acid in urine were significantly affected by the CUMS procedure and the 6 biomarkers were reversed evidently after administration of FFCGF. These changes were suggestion that the anti-depressant mechanism of FFCGF was associated with energy metabolism, lipid metabolism and amino acid metabolism.
Subject(s)
Animals , Male , Mice , Antidepressive Agents , Chemistry , Pharmacology , Therapeutic Uses , Behavior, Animal , Body Weight , Carbon Dioxide , Chemistry , Depression , Drug Therapy , Drugs, Chinese Herbal , Chemistry , Pharmacology , Therapeutic UsesABSTRACT
OBJECTIVE@#To investigate the role of T help 17 cells (Th17) and STAT3-VEGF pathway in pathogenesis of psoriasis.@*METHODS@#A total of 50 cases of psoriasis guinea pigs and 20 normal guinea pigs were selected. The ratio of Th17/ IL-17 cell in peripheral blood were detected by flow cytometric analysis; STAT3 and VEGF concentrations were measured by immunohistochemistry and Western blot.@*RESULTS@#The expression of Th17 in peripheral blood were significantly increased in psoriasis [(1.76±0.88)%] compared with controls [(0.48±0.27)%] (P<0.05). Th17 related cytokine STAT3 and VEGF were significantly increased in psoriasis compared with controls (P<0.05), and were positively correlated the expression of Th17.@*CONCLUSIONS@#The expressions of Th17, STAT3 and VEGF are elevated in psoriasis, which suggests Th17 cells have a potential role in the pathogenesis of psoriasis by STAT3-VEGF pathway.
Subject(s)
Animals , Cell Differentiation , Physiology , Disease Models, Animal , Guinea Pigs , Psoriasis , Metabolism , Pathology , STAT3 Transcription Factor , Blood , Metabolism , Signal Transduction , Skin , Chemistry , Cell Biology , Metabolism , Th17 Cells , Cell Biology , Vascular Endothelial Growth Factor A , Blood , MetabolismABSTRACT
Along with the enactment of a law separating the prescribing and dispensing of drugs in Korea in 2000, attempts at reducing medical expenses by generic substitution have been allowed since August 2001 so long as generic products are bioequivalent to the original products. In the pharmaceutical industry, the required development and investment to make generic products are much less in terms of time and money. Thus, the number of bioequivalence studies in Korea has increased. This has resulted in the need for bioequivalence recommendations (guidelines), taking into account the circumstances of the Korean pharmaceutical industry. In this paper, we provide procedures for making bioequivalence determinations for individual products acting on the circulatory system (30 drugs, 2011), the components of which are widely accepted for the development of generic products in Korea. These recommendations correspond with international guidelines, such as those of the US FDA and EMEA. For the 30 drugs that act on the circulatory system, we examined each in terms of subject selection (healthy volunteers vs. patients), dosage strength, dosage route, analytes to measure, and evaluation parameters, and prepared bioequivalence recommendations for individual products through an analysis of many published papers, US FDA and EMEA guidelines, and clinical trial websites. Based on the bioequivalence recommendations for individual products, we had several meetings in which KFDA officers (members of the New Drug Research team and the Office of Generic Drugs), three pharmacy professors with expertise in drug analysis and pharmacokinetics, and three professors of medicine with extensive experience in clinical trials participated to confirm and discuss the contents. Finally, the bioequivalence recommendations for individual products were provided on the KFDA website. The individual bioequivalence recommendations have been used by KFDA officers in drug evaluations and bioequivalency testing to improve consistency, clarity, and professionalism in the drug evaluation process. These recommendations will be useful for domestic pharmaceutical companies by shortening the time and cost associated with bioequivalence studies, especially in terms of standardized trial designs, dosage forms, and analytical methods.
Subject(s)
Dosage Forms , Drug Evaluation , Drug Industry , Drug Substitution , Drugs, Generic , Investments , Jurisprudence , Korea , Pharmacy , Therapeutic EquivalencyABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of down-regulation of astrocyte elevated gene-1 (AEG-1) expression on cell proliferation and cell cycle of gastric carcinoma cells, and its possible molecular mechanism.</p><p><b>METHODS</b>Control siRNA and AEG-1 siRNA were transfected into gastric carcinoma SGC-7901 cells. 48 h after transfection, the cells were divided into 3 groups including untransfected, siRNA control and AEG-1 siRNA transfection groups. Expressions of AEG-1 mRNA and protein in the 3 group cells were detected by real-time quantitative PCR and Western blot. The changes of cell proliferation were examined using CCK-8 kit, and the cell cycle distribution was detected by flow cytometry. Finally, expressions of cell proliferation and cell cycle related proteins were detected by Western blot.</p><p><b>RESULTS</b>Real-time quantitative PCR and Western blot demonstrated that compared with the untransfected and siRNA control groups, expressions of AEG-1 mRNA and protein were significantly down-regulated in the AEG-1 siRNA transfection group (P < 0.05), but there was no significant difference between the untransfected and siRNA control groups (P > 0.05). Furthermore, in vivo experiment confirmed a significant down-regulation of AEG-1 protein in the AEG-1 siRNA transfection group (P < 0.05). In addition, AEG-1 siRNA obviously inhibited the proliferation of SGC-7901 cells at different time points after transfection with AEG-1 siRNA. The percentage of cells in G0/G1 phase in the AEG-1 siRNA transfection group [(61.26 ± 1.25)%] was significantly higher than those in the untransfected group [(46.17 ± 1.91)%] and siRNA control group [(46.46 ± 1.96)%], and there was a significant difference between them (all P < 0.001). Furthermore, the result of Western blotting revealed that down-regulation of AEG-1 expression evoked the down-regulation of cdk2 and cyclin D1 expressions and elevation of p21 expression in vitro and in vivo.</p><p><b>CONCLUSIONS</b>The inhibition of cell proliferation and cell cycle arrest mediated by down-regulation of AEG-1 expression may be closely associated with the changes of expression of cell cycle related proteins including cdk2, cyclin D1 and p21.</p>
Subject(s)
Animals , Female , Humans , Mice , Cell Adhesion Molecules , Genetics , Cell Cycle Checkpoints , Cell Line, Tumor , Cell Proliferation , Cyclin D1 , Metabolism , Cyclin-Dependent Kinase 2 , Metabolism , Cyclin-Dependent Kinase Inhibitor p21 , Metabolism , Down-Regulation , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , RNA Interference , RNA, Messenger , Metabolism , RNA, Small Interfering , Genetics , Stomach Neoplasms , Metabolism , Pathology , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of KIAA0101 protein in gastric carcinoma cells, and to explore the effects of its down-regulation on the cell proliferation, cell cycle and invasion.</p><p><b>METHODS</b>Western blot was used to detect KIAA0101 protein expression in three gastric carcinoma cell lines including MKN-28, SGC-7901 and MKN-45. KIAA0101 siRNA and control siRNA were utilized to transfect MKN-45 cells, respectively. CCK-8 was used to analyze the changes of cell proliferation, and flow cytometry to examine the changes of cell cycle distribution. Finally, Boyden chamber was used to detect the ability of cell invasion.</p><p><b>RESULTS</b>Relative level of KIAA0101 protein in MKN-45 cells was significantly higher than those in MKN-28 and SGC-7901 cells, and there was significant difference among the three cell lines (P < 0.05). The result of CCK-8 study demonstrated that, compared with untreated group and control siRNA group, the proliferation of MKN-45 cells in KIAA0101 siRNA group was significantly inhibited (P < 0.05). Additionally, the result of cell cycle analysis revealed that the percentage of cell number in G(0)/G(1) phase in KIAA0101 siRNA group [(61.47 ± 0.89)%] was significantly higher than those in untreated group [(47.43 ± 0.85)%] and control siRNA group [(48.43 ± 0.73)%; F = 271.653, P = 0.000]. Further, Boyden chamber assay showed that the cell numbers migrated to Matrigel in KIAA0101 siRNA group (61.51 ± 4.76) were significantly lower than those in untreated group (138.74 ± 10.16) and control siRNA group (132.93 ± 11.25; F = 65.949, P = 0.000).</p><p><b>CONCLUSIONS</b>Down-regulation of KIAA0101 expression leads to an inhibition of cell proliferation, cell cycle and cell invasion. It may provide a novel target for the treatment of patients with gastric carcinoma.</p>