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Aim To explore the effect of γ-ray on the mRNA,protein expression levels and metabolic activity level of the key drug metabolic enzyme CYP3A1 in rat liver. Methods Wistar rats were randomly divided into control group, 24 h post-radiation group and 72 h post-radiation group. The experimental group was exposed to total body irradiation of single 6 Gy γ-ray. Blood was collected from the orbital venous plexus for blood routine examination and biochemical analysis 24 h and 72 h after irradiation, and liver tissue was prepared for quantifying expression of CYP3A1 mRNA and liver-specific microRNA (miR-122-5p) through RT-PCR. The expression level of CYP3A1 protein was analyzed by Western blot, and the metabolic activity level of CYP3A1 detected by the specific substrate midazolam combined with LC-MS method. Results Com¬pared with the control group, the weights of the rats in the radiation group significantly decreased, and the number of white blood cells was markedly reduced. Simultaneously, the activities of alanine aminotrans-ferase and alkaline phosphatase continuously descended, as well as the levels of total bilirubin and bile acid significantly increased, which indicated that the liver may be damaged after radiation. The relative expression of CYP3A1 mRNA continued to increase significantly 24 h and 72 h after irradiation. CYP3A1 protein expression and metabolic activity levels showed an obvious increasing trend 24 h after irradiation, and rose significantly 72 h after irradiation compared with the control group. At the same time, the expression of miR-122-5p in liver of rats in the 24 h and 72 h post-radiation group continued to decrease rapidly compared with the control group. Conclusions γ-ray radiation may arouse damage effect on liver, which leads to the continuous up-regulation of the mRNA and protein expression levels of the capital metabolic enzyme CYP3A1 in liver tissue, as well as the elevation of the metabolic activity level. The regulatory mechanism might be related to miR-122-5p.
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Aim To predict the potential mechanism of ophiopogonin D (OPD) against pulmonary fibrosis by network pharmacology, and further verify it by experiment in vivo. Methods This study found that ophiopogon was the most frequently used drug in the treatment of pulmonary fibrosis with deficiency of Qi and Yin through data mining. In order to explore its material basis, network pharmacology analysis was carried out. A model of pulmonary fibrosis was established by bleomycin, and different concentrations of ophiopogonin D were administered to verify the results of the pharmacological network. Results Firstly, through network pharmacology analysis, it was found that mitophagy might be the potential target for ophiopogon to exert anti-pulmonary fibrosis effect. Meanwhile, network topology analysis showed that OPD had the greatest relationship with mitophagy. Animal experiments showed that OPD could relieve pulmonary fibrosis and reduce collagen deposition in mice. At the same time, the detection of mitophagy related proteins showed that the compound could increase the expression of PINK1 and Parkin proteins, reduce the content of P62 protein in lung tissue, and reduce the intracellular ROS level. Conclusions OPD can improve mitochondrial function and play an anti-pulmonary fibrosis role by promoting PINKl/Parkin dependent mitophagy in lung tissue.
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Recombinant humanized anti-ricin monoclonal antibody (MIL50) is a recombinant humanized monoclonal antibody targeting ricin. In this study, an ELISA method was used to establish a method for the determination of MIL50 in macaque serum, and a cross design method was used. Twelve rhesus monkeys were intravenously injected 1 mg·kg-1 test preparation (MIL50 freeze-died powder injection) and reference preparation (MIL50 liquid preparation) to determine the plasma concentration of MIL50 at different time points, and the pharmacokinetic parameters were analyzed to compare the pharmacokinetic characteristics of MIL50 liquid preparation and freeze-died powder injection in rhesus monkeys. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Chinese Academy of Medical Sciences and Use of Laboratory Animals and the regulations derived by the Animal Care and Welfare Committee of the Institute of Radiation Medicine, Academy of Military Medical Sciences (IACUC-DWZX-2020-503). The results showed that there was no significant difference between Cmax and AUC0-5d in the two groups. The liquid preparation was the reference preparation, with Cmax ratio of 101.6% and AUC0-5d ratio of 101.9%, the 90% confidence interval of Cmax was 79.42%-129.92%, and the 90% confidence interval of AUC0-5d was 85.72%-121.18%. These results suggested that different dosage forms of MIL50 had certain differences in the changes of blood drug concentration in rhesus monkeys.
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Objective:To explore the predictive value of low-dose biphasic (inspiratory and expiratory) CT air trapping sign and semi-quantitative score in predicting abnormal blood gas parameters and progression to severe disease in COVID-19 patients.Methods:Patients with non-severe COVID-19 who were diagnosed by nucleic acid testing and hospitalized in designated hospitals in Wuxi City from January 23 to February 29, 2020 were prospectively and consecutively recruited. All patients received low-dose biphasic CT examination on admission and repeated CT examination at regular intervals during the course. On the inspiratory phase admission of the bipolar CT, the scope of the lesion was evaluated by semi-quantitative score, and the air trapping sign on bipolar CT was assessed. The differences of semi-quantitative score, the presence of the air trapping sign and other clinical factors were compared between the patients with abnormal and the normal blood gas index, as well as between the cases progressed to severe disease and cases without disease progression using the independent sample t-test or χ 2 test. The area under the curve (AUC) of receiver operating characteristic (ROC) and the comprehensive discriminant improvement index (IDI) were used to evaluate the predictive effectiveness of the semi-quantitative scores, air trapping sign, and combination of two factors in differentiating cases with abnormal and normal blood gas indexes, as well as in differentiating cases with and without disease progression to severe COVID-19 cases. Results:In total 51 non-severe COVID-19 cases were included, with 16 cases showed air trapping sign during the first biphasic CT examination on admission. During the course of the disease, there were 13 patients with abnormal blood gas index, and 9 cases displaying air trapping sign (9/13). All 7 cases with progression to severe cases showed air trapping sign (7/7). Patients with advanced age, air trapping sign and higher semi-quantitative score were found more likely to have abnormal blood gas index ( t=3.10, χ 2=9.38, t=3.34, P<0.05); patients with advanced age, underlying diseases, air trapping sign and higher semi-quantitative score were more likely to develop into severe disease ( t=2.68, χ 2=6.65, χ 2=4.25, t=4.33, P<0.05). The AUC of semi-quantitative score, air trapping sign and combination of two factors in distinguishing abnormal blood gas index from normal blood gas index was 0.803, 0.754 and 0.794 respectively. The AUC of semi-quantitative score, air trapping sign and combination of two factors in distinguishing cases with progression to severe cases from non-progression was 0.881, 0.898 and 0.932, respectively. Air trapping sign combined with semi-quantitative score significantly improved the prediction effectiveness of disease progression, compared with semi-quantitative score or air trapping sign (IDI=0.271, 0.117). Conclusion:Air trapping sign and semi-quantitative score might be used as effective indicators to predict the progression of COVID-19 cases, and the combination of these two factors might be more helpful to predict the disease progression.
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Objective:To study the influence of objective structured clinical examination (OSCE) assessment mode on learning interest and critical thinking of nursing students in operating room.Methods:There were 49 operating room nursing students from April 2019 to April 2020 who were selected as the observation group, receiving the teaching and assessment mode of OSCE. In addition, 49 operating room nursing students from March 2018 to March 2019 were included as the control group, receiving the conventional teaching and assessment mode. The nursing students' learning attitude scale was used to compare the learning interest of the two groups, and the critical thinking level of nursing students was recorded by Chinese critical thinking disposition inventory-Chinese version (CTDI-CV). SPSS 24.0 software was used to analyze the data with t test and chi-square test. Results:There were statistically significant differences in the scores of learning interest, learning experience, learning habits, professional cognition and the total scores of the learning attitude of nursing students after the assessment between the observation group and the control group ( t=4.861, t=4.885, t=3.466, t=4.206, t=8.292; all P<0.05). There were statistically significance of curiosity, truth seeking, open thinking, analytical ability, systematic ability, self-confidence in thinking, cognitive maturity and the CTDI-CV total scores after the assessment between the observation group and the control group ( t=4.262, t=4.311, t=2.754, t=4.854, t=3.984, t=2.864, t=4.267, t=2.729; P<0.05). Conclusion:The OSCE assessment mode used in operating room for nursing students is helpful to improve the learning interest and the cultivation of students' critical thinking.
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Objective@#To understand the filialpiety values, anxiety and caregiving burden of caregivers of patients with chronic heart failure and to analyze the mediating effect of filialpiety values on the relationship between anxiety and caregiving burden.@*Methods@#During April 2017 to April 2018, 191children caregivers of patients with chronic heart failure from 3 secondary and tertiary medical institutions in Suzhou, Nanjing and Kunshan were selected to complete Visual Analogue Scale for Anxiety, Chinese Filial Values Index scale (FVI) and Dutch Objective Burden Inventory (DOBI).@*Results@#The total score of caregivers' anxiety, filialpiety values and caregiving burden were 3(0, 6), 96(84, 107) and 1(0, 9) respectively. Correlation analysis showed that the caregivers' anxiety was positively correlated with the caregiving burden (r=0.328, P<0.01), while filialpiety values were negatively correlated with caregiving burden (r=-0.537, P<0.01). Mediating-effect analysis showed that anxiety had a negative effect on filialpiety values (a=-0.61, P=0.02), and had a positive effect on caregiving burden (c=0.64, P=0.01). The filialpiety values had a negative effect on caregiving burden (b=-0.43, P<0.01). Filialpiety values played a partial mediating role between anxiety and caregiving burden (c' = 0.26, P<0.05).@*Conclusions@#Medical staff should establish targeted interventions to improve caregivers′ filialpiety values, thereby reducing their caregiving burden.
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Objective To investigate and analyze the prevalence, patterns and associated factors of domestic violence against married women in Wenzhou area. Methods a total of 705 married women took part in this cross-sectional study conducted in 2018. Conflict Tactics Scales and several short demographic questions were used in this study to collect basic information and the occurence of domestic violence within 12 months. Results Nearly 40% of married women experienced at least one incident of domestic violence during the past 12 months. 33.8% of respondents experiencing one episode of psychological violence in the past 12 months, followed by 19.5% experienced physical violence and 14.9%of sexual violence. The joint occurrence of multiple forms of violence was the most commonly reported features experiencing domestic violence. Some individual (education and Hukou), marital relationship (marital satisfaction, duration of marriage, marital autonomy marital models) and family (family model and sex roles) factors of the respondents, were negatively or positively associated with domestic violence against married women. Conclusion The results indicated that there was a high rate of domestic violence among married women in Wenzhou area. Accordingly, there is an obvious need of intervention and treatment activities to prevent and reduce the occurrence of domestic violence among the married women.
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Objective To understand the filialpiety values, anxiety and caregiving burden of caregivers of patients with chronic heart failure and to analyze the mediating effect of filialpiety values on the relationship between anxiety and caregiving burden. Methods During April 2017 to April 2018, 191children caregivers of patients with chronic heart failure from 3 secondary and tertiary medical institutions in Suzhou, Nanjing and Kunshan were selected to complete Visual Analogue Scale for Anxiety, Chinese Filial Values Index scale (FVI) and Dutch Objective Burden Inventory (DOBI). Results The total score of caregivers' anxiety, filialpiety values and caregiving burden were 3(0, 6), 96(84, 107) and 1(0, 9) respectively. Correlation analysis showed that the caregivers' anxiety was positively correlated with the caregiving burden (r=0.328, P<0.01), while filialpiety values were negatively correlated with caregiving burden (r=-0.537, P<0.01). Mediating-effect analysis showed that anxiety had a negative effect on filialpiety values (a=-0.61, P=0.02), and had a positive effect on caregiving burden (c=0.64, P=0.01). The filialpiety values had a negative effect on caregiving burden (b=-0.43, P<0.01). Filialpiety values played a partial mediating role between anxiety and caregiving burden (c' = 0.26, P＜0.05). Conclusions Medical staff should establish targeted interventions to improve caregivers′filialpiety values, thereby reducing their caregiving burden.
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Objective To report the surgical nursing strategy of a patient undergoing resection of a rare giant neurofibroma.Methods Through the preoperative comprehensive assessment of patients,multidisciplinary joint consultation and proposed possible surgical risks and countermeasures,specialist to formulate surgical plans,surgical care and nursing key points,difficulties and countermeasures.Results The psychological nursing,detailed and perfect the preoperative preparation work,the personnel allocation was sufficient,the division of labor was clear,the disease changes were actively observed in the operation,the venous pathway was strictly managed,the accurate record,the risk that might occur in the active prevention operation and the treatment plan,the postoperative closely monitors the condition.Good observation and nursing in the operation area to prevent infection.Conclusions In view of difficult and complicated operation,through the comprehensive formulation of surgical nursing measures and strict execution in surgery,it is the guarantee for the smooth completion of the operation,the operation process is smooth,the successful implementation of tumor resection,the effect is satisfactory,the patient is returned to the ward,and there is no special discomfort.
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Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC 120 nmol·L) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.
Subject(s)
Animals , Female , Humans , Male , Mice , Abietanes , Chemistry , Analgesics , Chemistry , Chronic Pain , Drug Therapy , Drug Evaluation, Preclinical , Enzyme Inhibitors , Chemistry , Mice, Inbred ICR , Monoacylglycerol Lipases , Metabolism , Structure-Activity RelationshipABSTRACT
Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC 120 nmol·L) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.
Subject(s)
Animals , Female , Humans , Male , Mice , Analgesics , Chemistry , Chronic Pain , Drug Therapy , Abietanes , Chemistry , Drug Evaluation, Preclinical , Enzyme Inhibitors , Chemistry , Mice, Inbred ICR , Monoacylglycerol Lipases , Metabolism , Structure-Activity RelationshipABSTRACT
Objective To evaluate the value of a novel laser navigation system (LNS) designed for a SPECT/ CT platform in improving efficiency of molecular imaging-guided percutaneous transthoracic needle biopsy (PTNB). Methods From January 2017 to October 2017, a total of 25 patients (17 males, 8 fe-males, age (58.9±10.8) years) with thoracic lesions suspicious for malignancy underwent 99 Tcm-methoxy-isobutylisonitrile (MIBI) SPECT/ CT-guided PTNB, and the hyperactivity areas were chosen as the sam-pling areas. Thirteen patients underwent traditional free hand puncture (control group), and 12 patients had LNS-assisted puncture (LNS group). The operation time, CT-guided times, average effective radiation dose of the two methods were compared. Two-sample t test was used to analyze the data. Results Comparing to control group, LNS-assisted PTNB puncture significantly reduced operation time ((7.6±2.2) vs (24. 2± 9. 8) min; t= 5.693, P<0.001), CT-guided times (1.9±0.9 vs 4.0±1.5; t= 4.108, P<0.001) and average effective radiation dose ((7.7±0.9) vs (10.5±2.1) mSv; t= 4.306, P<0.01). Conclusion The novel LNS is helpful in improving efficiency of molecular imaging-guided PTNB based on a SPECT/ CT platform.
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Mangosteen (Garcinia mangostana Linn.) is a well-known tropical tree indigenous to Southeast Asia. Its fruit's pericarp abounds with a class of isoprenylated xanthones which are referred as mangostins. Numerous in vitro and in vivo studies have shown that mangostins and their derivatives possess diverse pharmacological activities, such as antibacterial, antifungal, antimalarial, anticarcinogenic, antiatherogenic activities as well as neuroprotective properties in Alzheimer's disease (AD). This review article provides a comprehensive review of the pharmacological activities of mangostins and their derivatives to reveal their promising utilities in the treatment of certain important diseases, mainly focusing on the discussions of the underlying molecular targets/pathways, modes of action, and relevant structure-activity relationships (SARs). Meanwhile, the pharmacokinetics (PK) profile and recent toxicological studies of mangostins are also described for further druggability exploration in the future.
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Animals , Humans , Anti-Infective Agents , Pharmacology , Anticarcinogenic Agents , Pharmacology , Antineoplastic Agents, Phytogenic , Pharmacology , Antioxidants , Pharmacology , Cardiovascular Agents , Pharmacology , Fruit , Chemistry , Garcinia mangostana , Chemistry , Neuroprotective Agents , Pharmacology , Phytotherapy , Plant Extracts , Pharmacology , Protective Agents , Pharmacology , Xanthones , PharmacologyABSTRACT
Objective To discuss the effect of two different warming methods on the circulation of free flaps during operation and seek for an optimal warming method which is benificial for the circulation of free flaps, and thus provide clinical evidences for intraoperative care. Methods A total of 96 patients undergoing free flap transplantation were divided into routine warming group and diversification warming group randomly (n=48 each). In routine warming group, temperature in the operating room was set at routine temperature and flaps were douched by routine heated saline. In diversification warming group, the temperature in the operation room, fluids used for washing wounds and flaps were warmed, fluids for intravenous application were pre-warmed by a fluid warmer, in addition, the operation table where patients were lying on was covered with warmer blanket. The influence of two different warming methods on the circulation of free flaps was observed. Results The scores of flap elasticity and capillary refill time in routine warming group were 2.02 ± 0.79 and 2.04 ± 0.81, respectively, vs. 2.50 ± 0.61 and 2.48 ± 0.6 in diversification warming group, showing diversification warming group was statistically better than routine warming group (Z=1.949, 3.872, P<0.05). In addition, the flap survival rate in routine warming group was 81.2%(39/48) vs. 95.8%(46/48) in diversification warming group, showing significantly better results in diversification warming group (χ2=4.02, P < 0.05). Conclusions The diversification warm keeping method can effectively promote the circulation and survival of flaps, improve clinical prognosis, accelerate postoperative rehabilitation, therefore is worthy of being recommanded its clinical application.
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As a widespread phenomenon in living system, molecular self-assembly has become the meeting point of multidisciplinary research including chemistry, biology, materials science and medicine. In recent years, the rapid development in molecular self-assembly of peptide technology is showing a great potential in the application of tissue engineering, drug delivery, bionic medicine, cosmetology field, optical and electronic product development, etc. Especially, the remarkable hemostatic effect of self-assembling peptides (SAP) on organs, nerves and brain wounds successfully promoted its application to the material science and clinical medicine. This review focuses on the hemostatic effects and characteristics of SAP on different bleeding wound models, action mechanism, its benefits and limitations as well as its adrancing trends.
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Humans , Drug Delivery Systems , Hemostasis , Peptides , Tissue EngineeringABSTRACT
A rapid, sensitive and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of yogliptin and its metabolite in Wistar rat plasma. Linagliptin and dexamethasone were chosen as the internal standards of yogliptin and its metabolite, (R)-8-(3-hydroxypiperidine- -yl)-7-(but-2-yn-1-yl)-1-((5-fluorobenzo[d]thiazol-2-yl)methyl)-3-methyl- H-purine-2, 6 (3H, 7H)-dione, respectively. After a simple protein precipitation using acetonitrile as the precipitating solvent, both analytes and ISs were separated on a Grace Altima HP C18 column (2.1 mm x 50 mm, 5 microm) with gradient elution using methanol (containing 0.1% formic acid, 4 mmol x L(-1) ammonium acetate)-0.1% formic acid (containing 4 mmol x L(-1) ammonium acetate) as the mobile phase. A chromatographic total run time of 4.4 min was achieved. Mass spectrometric detection was conducted with electrospray ionization under positive-ion and multiple-reaction monitoring modes. Linear calibration curves for yogliptin and its metabolite were over the concentration range of 0.5 to 500 ng x mL(-1) with a lower limit of quantification of 0.5 ng x mL(-1). The intra- and inter- assay precisions were all below 14%, the accuracies were all in standard ranges. The method was used to determine the concentration of yogliptin and M1 in Wistar rat plasma after a single oral administration of yogliptin (27 mg x kg(-1)). The method was proved to be selective, sensitive and suitable for pharmacokinetic study of yogliptin and M1 in Wistar rat plasma.
Subject(s)
Animals , Rats , Chromatography, Liquid , Dexamethasone , Blood , Dipeptidyl-Peptidase IV Inhibitors , Blood , Pharmacokinetics , Linagliptin , Blood , Rats, Wistar , Tandem Mass SpectrometryABSTRACT
Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.
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Animals , Dogs , Male , Area Under Curve , Batroxobin , Blood , Pharmacokinetics , Pharmacology , Enzyme-Linked Immunosorbent Assay , Fibrin Fibrinogen Degradation Products , Metabolism , Fibrinogen , Metabolism , Fibrinolytic Agents , Blood , Pharmacokinetics , Pharmacology , Infusions, Intravenous , Partial Thromboplastin Time , Prothrombin Time , Thrombin TimeABSTRACT
<p><b>OBJECTIVE</b>To elucidate the possible mechanism of oral carcinogenesis and to explore the value of clinical application of the detection of cytokeratin (CK) 19 for oral squamous cell carcinoma (OSCC) patients.</p><p><b>METHODS</b>The cancerous tissues, para-cancerous tissues and excised lymph nodes were collected from 20 operated patients with OSCC. The patients didn't receive radiotherapy and chemotherapy before hospitalization. The relative expression of CK19 mRNA in those tissues was detected by fluorescent quantitative polymerase chain reaction (FQ-PCR).</p><p><b>RESULTS</b>The expression of CK19 mRNA in the cancerous tissues was 1.85 and 1.66 times higher than that in normal oral mucosa and in para-cancerous tissues, respectively. The expression of CK19 mRNA in lymph nodes from 9 patients with OSCC was positive and the positive rate was 45% (9/20). The positive rate of CK19 mRNA in all lymph nodes from 9 patients with OSCC was 81.8% (18/22), and the positive rate of CK19 mRNA in all lymph nodes from 20 patients with OSCC was 41.9%(18/43). CK19 mRNA level in the cancerous tissues relative to para-cancerous tissues and normal oral mucosa of the patients whose CK19 mRNA expression was positive was lower than that of the patients whose CK19 mRNA expression was negative in lymph nodes, respectively.</p><p><b>CONCLUSION</b>The possible reason that the expression of CK19 mRNA in the cancerous tissues was higher than that in para-cancerous tissues and normal oral mucosa was that the CK19 synthesis in cancerous tissues increased obviously. The detection of CK19 mRNA in lymph nodes was regarded probably as one of the markers for detecting OSCC micrometastasis in lymph nodes. The detection of CK19 mRNA in lymph nodes by FQ-PCR was more sensitive than hematoxylin-eosin staining in diagnosing OSCC micrometastasis.</p>
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Female , Humans , Male , Middle Aged , Carcinoma, Squamous Cell , Keratin-19 , Mouth Mucosa , Mouth Neoplasms , RNA, MessengerABSTRACT
<p><b>OBJECTIVES</b>Programmed death-1 (PD-1) up-regulation impairs virus-specific CD8+ T-cell responses during chronic viral infection. Whether PD-1 expression influences the virus-specific CD8+ T cells in humans with acute viral infection remains largely undefined. This study aims to characterize the PD-1 expression during acute hepatitis B (AHB), and further addresses the association between the PD-1 dynamics and memory T-cell formation during acute HBV infection.</p><p><b>METHODS</b>Peripheral HBV-specific CD8+ T cells from 11 HLA-A2-positive AHB patients were longitudinally quantitatively analyzed, and PD-1, memory markers CCR7, CD45RA and CD127 and activation marker CD38 on HBV-specific CD8+ T cells were measured using flow cytometric assay. Serum ALT, HBsAg, HBsAb and HBV-DNA levels were evaluated for each subject.</p><p><b>RESULTS</b>All 11 AHB patients examined had multiple pentamer-positive CD8+ T-cell responses in their early phase of HBV infection. Specifically, their PD-1 on pentamer-positive CD8+ T-cells was significantly up-regulated at the onset of their disease. Following their disease resolution, the dynamic decrease in PD-1 expression was found to correlate with the phenotypic development of memory CD8+ T cells, indicated by the increases in CCR7, CD45RA and CD127 and decrease in CD38.</p><p><b>CONCLUSION</b>PD-1-mediated negative signaling may be closely associated with memory T-cell formation during acute self-limited hepatitis B.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Acute Disease , Antigens, CD , Metabolism , Apoptosis Regulatory Proteins , Metabolism , Hepatitis B , Allergy and Immunology , Metabolism , Immunologic Memory , Programmed Cell Death 1 Receptor , T-Lymphocytes, Cytotoxic , Allergy and Immunology , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To evaluate the feasibility of localizing the internal auditory canal (IAC) and the facial nerve through the root of the zygoma, foramen spinosum and the head of the malleus in middle fossa approach with the assistance of high resolution computerized tomography (HRCT).</p><p><b>METHODS</b>Eighteen human cadaveric temporal bones were scanned and measured by HRCT. Cadaver specimen were divided into two groups. Group A was studied first through a middle fossa approach to find out the relationship between the HRCT measurements and the anatomic measurements. Then 4 whole human cadaveric heads (8 temporal bones) of group B were dissected using a HRCT oriented middle fossa approach to localize IAC with the root of the zygoma, foramen spinosum and the head of the malleus as landmarks. The two measurement methods were analysed with the Paired-Sample T test, and the difference was thought to be statistical significant when P < 0.05.</p><p><b>RESULTS</b>In Group A, there were no statistical significant differences between the CT measurements and the anatomic measurements from the head of the malleus to other important anatomic structures. In group B, the operation was guided with CT measurements: the distance between the head of the malleus and the root of the zygoma, and the distance between the head of the malleus and foramen spinosum. Within the range 1.5 mm to 3.7 mm, the head of malleus was correctly localized. In seven out of the eight cases, the root of the zygoma, the head of the malleus and the internal auditory canal were in a straight line, whereas, in one case, there was an angle of 15 degrees between the root of zygoma -head of malleus line and head of malleus -internal auditory canal line.</p><p><b>CONCLUSIONS</b>HRCT would provide more information on the distance relationship between the head of malleus and the root of the zygoma, foramen spinosum and the internal auditory canal. The head of the malleus could be localized through the root of the zygoma and foramen spinosum with HRCT and therefore the IAC could be exposed with the head of the malleus as a landmark in middle fossa approach when other landmarks were not recognizable.</p>