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NSCs play an essential role in the regeneration process of the central nervous system. However, due to the influence of the harsh pathological microenvironment, the viability of neural stem cells is limited, and the therapeutic effect needs improvement. Previous studies have found that stem cells overexpressing ciliary neurotrophic factor (CNTF) have apparent therapeutic effects on remyelination, but the specific mechanism of action still needs to be further explored. We found that astrocytes, the most numerous groups in the CNS, exhibited a pathological role in the experimental autoimmune encephalomyelitis model, but after stimulation with CNTF-NSCs, a phenotypic switch occurred and induced the neurotrophic factor cardiotrophin-like cytokine 1 (Clcf1) production. Mechanistically, Clcf1 can significantly promote the differentiation of oligodendrocyte precursor cells (OPCs), and the advanced effect can attenuate by the Clcf1 antibody. Therefore, this study was conducted to investigate the pathway by which CNTF-NSCs exert their therapeutic effects by affecting astrocytes. It is expected to identify a potential therapeutic factor, Clcf1, for the treatment of demyelinating diseases.
Subject(s)
Neural Stem Cells , Oligodendrocyte Precursor Cells , Ciliary Neurotrophic Factor/pharmacology , Oligodendrocyte Precursor Cells/metabolism , Astrocytes/metabolism , Cell Differentiation , Neural Stem Cells/metabolism , OligodendrogliaABSTRACT
Objective: To investigate the clinical value of coefficient of variation of heart rate and blood pressure in rapid identification of children with suspected orthostatic intolerance(OI). Methods: This was a retrospective study. The medical records of 379 children with OI were collected, who were admitted to the Department of Pediatrics of Qilu Hospital of Shandong University from January 2015 to January 2020. Another 20 out-patient children without syncope or syncope aura were selected as control. According to the results of standing test and head-up tilt test (HUTT), all the patients with OI were divided into the following 4 groups: vasovagal syncope (VVS) group, postural tachycardia syndrome (POTS) group, POTS combined with VVS (POTS+VVS) group and HUTT negative group. Then, coefficient of variation of systolic pressure (SBPCV), coefficient of variation of diastolic pressure (DBPCV) and coefficient of variation of heart rate (HRCV) in standing test and HUTT were calculated. Kruskal-Wallis test was used for comparison among the five groups, and Dunnett's T3 method for comparison between two groups. Paired t test was used to compare the coefficient of variation between supine and erect position and tilt position in each group. The predictive values of HRCV,SBPCV and DBPCV for negative HUTT were evaluated by receiver operating characteristic (ROC) curve. Results: Among the 379 children, there were 79 in HUTT negative group, 208 in VVS group, 52 in POTS group, and 40 in POTS+VVS group. The SBPCV of supine-erect position of the control group, HUTT negative group, VVS group, POTS group, POTS+VVS group were (3.8±1.0)%, (5.3±2.2)%, (6.6±3.4)%, (5.9±3.6)%, (6.9±2.8)%, respectively. Similarly, the SBPCV of supine, erect and head-up tilt position were (4.5±0.8)%, (6.0±1.9)%, (7.1±2.6)%, (6.0±2.1)%, (7.3±2.5)%; the DBPCV of supine-erect position were (7.3±1.2)%, (9.1±3.7)%, (9.1±4.9)%, (9.1±4.8)%, (11.6±4.6)%; the DBPCV of supine, erect and tilt position were (7.4±1.1)%, (9.4±2.9)%, (10.1±3.8)%, (9.2±3.3)%, (11.0±4.7)%; the HRCV of supine-erect position were (7.6±2.6)%, (12.9±3.7)%, (16.2±4.3)%, (21.2±5.9)%, (24.9±5.3)%; and the HRCV of supine, erect and tilt position were (8.1±1.6)%, (10.1±2.7)%, (14.1±4.3)%, (15.6±3.7)%, (18.9±4.0)%, respectively. All the indexes showed significant differences among the five groups (χ2=21.91, 25.47, 19.82, 14.65, 104.52, 92.51, all P<0.05). ROC curve analysis showed that when the SBPCV and HRCV of supine-erect position reached 4.4% and 10.5%, the area under the curve of ROC were 0.713 and 0.877, the sensitivity of predicting negative HUTT were 58.2% and 78.5%, and the specificity were 80.0% and 95.0%, respectively. Conclusions: Coefficient of variation of heart rate and blood pressure may serve as potential diagnostic indexes in evaluating autonomic function of OI patients. SBPCV ≥ 4.4% or HRCV ≥ 10.5% of supine-erect position could be an indication of HUTT.
Subject(s)
Child , Humans , Blood Pressure , Heart Rate , Orthostatic Intolerance/diagnosis , Postural Orthostatic Tachycardia Syndrome/diagnosis , Retrospective Studies , Syncope, Vasovagal/diagnosis , Tilt-Table TestABSTRACT
OBJECTIVE@#To investigate how the National Health Commission of China (NHCC)-recommended Chinese medicines (CMs) modulate the major maladjustments of coronavirus disease 2019 (COVID-19), particularly the clinically observed complications and comorbidities.@*METHODS@#By focusing on the potent targets in common with the conventional medicines, we investigated the mechanisms of 11 NHCC-recommended CMs in the modulation of the major COVID-19 pathophysiology (hyperinflammations, viral replication), complications (pain, headache) and comorbidities (hypertension, obesity, diabetes). The constituent herbs of these CMs and their chemical ingredients were from the Traditional Chinese Medicine Information Database. The experimentally-determined targets and the activity values of the chemical ingredients of these CMs were from the Natural Product Activity and Species Source Database. The approved and clinical trial drugs against these targets were searched from the Therapeutic Target Database and DrugBank Database. Pathways of the targets was obtained from Kyoto Encyclopedia of Genes and Genomes and additional literature search.@*RESULTS@#Overall, 9 CMs modulated 6 targets discovered by the COVID-19 target discovery studies, 8 and 11 CMs modulated 8 and 6 targets of the approved or clinical trial drugs for the treatment of the major COVID-19 complications and comorbidities, respectively.@*CONCLUSION@#The coordinated actions of each NHCC-recommended CM against a few targets of the major COVID-19 pathophysiology, complications and comorbidities, partly have common mechanisms with the conventional medicines.
Subject(s)
Humans , COVID-19/physiopathology , Comorbidity , Drugs, Chinese Herbal/therapeutic use , Medicine , Medicine, Chinese Traditional , SARS-CoV-2ABSTRACT
Neonatal seizures are the most common clinical manifestations of critically ill neonates and often suggest serious diseases and complicated etiologies. The precise diagnosis of this disease can optimize the use of anti-seizure medication, reduce hospital costs, and improve the long-term neurodevelopmental outcomes. Currently, a few artificial intelligence-assisted diagnosis and treatment systems have been developed for neonatal seizures, but there is still a lack of high-level evidence for the diagnosis and treatment value in the real world. Based on an artificial intelligence-assisted diagnosis and treatment systems that has been developed for neonatal seizures, this study plans to recruit 370 neonates at a high risk of seizures from 6 neonatal intensive care units (NICUs) in China, in order to evaluate the effect of the system on the diagnosis, treatment, and prognosis of neonatal seizures in neonates with different gestational ages in the NICU. In this study, a diagnostic study protocol is used to evaluate the diagnostic value of the system, and a randomized parallel-controlled trial is designed to evaluate the effect of the system on the treatment and prognosis of neonates at a high risk of seizures. This multicenter prospective study will provide high-level evidence for the clinical application of artificial intelligence-assisted diagnosis and treatment systems for neonatal seizures in the real world.
Subject(s)
Humans , Infant, Newborn , Artificial Intelligence , Electroencephalography/methods , Epilepsy/diagnosis , Infant, Newborn, Diseases/diagnosis , Intensive Care Units, Neonatal , Multicenter Studies as Topic , Prospective Studies , Randomized Controlled Trials as Topic , Seizures/drug therapyABSTRACT
In China, about 100 million people currently have chronic obstructive pulmonary disease (COPD). At the same time, COPD is a multisystem disease, not only affecting the function of musculoskeletal, cardiovascular, kidney and immune systems in patients, but also causing intestinal dysfunction as its extrapulmonary manifestations. From the perspective of traditional Chinese medicine (TCM), after COPD is formed, deficiency, phlegm stasis and toxicity were accumulated in the lungs, which leads to dysfunction of lung in dispersing and descending, and eventually causes ascending and descending disorder of Qi activities, disorder of fluid supply and distribution, and stagnation of blood stasis. The viscera disease would affect the bowels, and the large intestine is thus affected. Modern medical discovers that, the lungs and intestines have common origins and similar physiological structures, in pathological circumstances, their common mucosal immune system may lead to similar immune factors and inflammatory manifestations in the lungs and intestines. At the same time, the studies have confirmed that there is also a close relationship between intestinal flora and lung, that is "lung-gut axis". These theories partially illustrate the mechanism of COPD in inducing intestinal injury. The specific manifestations of COPD intestinal dysfunction, ① Flora disorder, with increased abundance of intestinal gram-negative bacilli, and inhibited reproduction of Bifidobacterium, Lactobacillus and short-chain fatty acid-producing bacteria. ② Intestinal barrier damage: characterized by the destruction of intestinal epithelium tight connectivity, increased intestinal permeability, and thinning of the mucus layer. ③ Intestinal motility disorder: mostly manifested as weight loss and malnutrition. At present, for the intestinal dysfunction in COPD patients, most of the relevant discussions and targeted treatment methods in TCM are scattered and unsystematic. Guided by the idea of treating different diseases with the same treatment, we summarized the etiology and pathogenesis of COPD intestinal dysfunction by learning from the experience of TCM in treating intestinal flora disorders and inflammatory bowel disease, and proposed preliminary formulation with Tiaoqi Qushi,Tongfu Tongluo as its basic treatment principles in this paper, hoping to provide new ideas for the treatment of COPD.
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Since the outbreak of Novel Coronavirus Pneumonia(NCP), hospitals have taken the fight against the virus as its own responsibility, and keep standing in the front line of epidemic prevention and control. The continuous input of anti-epidemic forces in hospitals also brings challenges to the medical supplies support, including the management of protective supplies and the maintenance of medical equipment. In the face of increasing security pressure, the medical materials support team broke the game on multiple fronts. Firstly, the team implements active material procurement strategy, sets material distribution priority according to risk level, releases materials uniformly based on stock and use, and implements traceability management of donated materials to ensure material supply. Secondly, centralized allocation management of equipment, emergency installation, advanced maintenance and emergency maintenance work is effectively completed. Thirdly, disinfection strategies for items and equipment are developed safely and effectively with the aid of disinfection equipment functions. At last, personnel management and training have been strengthened. These measures have provided strong support for the orderly prevention and control of the epidemic.
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Objective:To investigate the role of IL-1β in regulating human placenta-derived mesenchymal stem cells (hPMSCs) to induce the differentiation of activated peripheral blood mononuclear cells (PBMCs) into CD8 + IL-10 + T cell subset in patients with rheumatoid arthritis (RA). Methods:Serum IL-1β levels in RA patients were detected by CBA kit. hPMSCs were isolated from healthy subjects by enzyme digestion. PBMCs that were isolated from RA patients and healthy subjects by Ficoll density gradient centrifugation were activated with PHA and CD3/CD28 monoclonal antibody (McAb) and then co-cultured with hPMSCs. Flow cytometry (FCM) was used to analyze the ability of hPMSCs to induce the differentiation of activated PBMCs into CD8 + IL-10 + T cell subset with the presence of programmed death ligand 1 (PD-L1) and/or PD-L2 McAb and IL-1β. Expression of PD-L1 and PD-L2 on hPMSCs under IL-1β stimulation was analyzed by RT-PCR and FCM. Results:Serum IL-1β levels were significantly higher in RA patients than in healthy subjects. After the activation by PHA and CD3/CD28 McAb, the proportion of CD8 + IL-10 + T cells in PBMCs of RA patients was significantly lower than that of healthy subjects. Moreover, the proportion of CD8 + IL-10 + T cells significantly increased after co-cultured with hPMSCs. The ability of IL-1β-treated hPMSCs to induce activated PBMCs to differentiate into CD8 + IL-10 + T cells was significantly enhanced compared to untreated hPMSCs. IL-1β could up-regulate the expression of PD-L1 and PD-L2 on hPMSCs. Blocking the expression of PD-L1 and/or PD-L2 on hPMSCs significantly reduced the ability of hPMSCs to induce activated PBMCs to differentiate into CD8 + IL-10 + T cells. Conclusions:IL-1β enhanced the capacity of hPMSCs to induce activated PBMCs to differentiate into CD8 + IL-10 + T cells in RA patients by up-regulating the expression of PD-L1 and PD-L2.
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Since the outbreak of COVID-19, the hospital is faced with such challenges as sustained input in patient screening, referral and rescue, supportive medical supplies including the management of personal protective supplies and the maintenance of medical equipment. In the face of increasing workload, the medical materials support team of the hospital took the following measures in the principles of " discovering new sources of supplies and minimizing consumption" . These measures taken include proactive supply procurement strategy, prioritizing allocations based on risk exposure, uniform distribution of supplies based on inventory and usage, and traceable management for donated supplies; optimal and central deployment of equipments, emergency installation, pre-maintenance and emergency repairs for equipments; efficient and safe sterilization of reusable materials and equipments using sterilizers; enhanced personnel training and management to keep updating the medical supplies capacity of the team. All these efforts have contributed significantly to the orderly work of epidemic control.
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The growing epidemic of drug-resistant tuberculosis has posed a great threat to people′s health and become a major public health and social problems. Early detection and standardized treatment of tuberculosis are of great significance to controlling its spread. In order to provide reference for better prevention and clinical treatment of tuberculosis,this paper reviews the current situa-tion of anti-tuberculosis drugs and mechanism of resistance and new potential drugs for treating tuberculosis.
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Objective To evaluate the protective efficacy of influenza vaccine in the elderly in China. Methods The Chinese databases (CNKI, Wan Fang, VIP) and English databases (Pubmed, Embase) were searched, then studies related to the protective efficacy of influenza vaccine in the elderly according to pre-designed criteria were included and the vaccine efficacy(VE) was selected as an evaluation index. Rev Man 5.3 and Stata 12.0 were used in this meta analysis. Results A total of 26 studies (2000-2016) including 6 kinds of outcomes were eligible, of which, 22 articles related to influenza like illness (ILI) , 5 articles related to common cold (CC) , 11 articles related to the attendance rate due to ILI and CC, 7 articles about chronic diseases (including Hypertension, Diabetes, Coronary Heart Disease (CHD) , Stroke, Cancer, Chronic bronchitis and others) , 6 articles about chronic disease treatment and 3 articles about all-cause mortality. The VE of influenza vaccine was 58.00% (95%CI: 48.00%-66.00%), 40.00%(95% CI: 30.00%-50.00%), 42.00% (95% CI: 34.00%-49.00%), 17.00% (95% CI: 11.00%-23.00%), 28.00%(95% CI: 14 .00 % -40.00 %) and 28 .00 % (95% CI: 15 .00 % -39 .00 %) , respectively. Conclusion Influenza vaccination can effectively prevent the occurrence of influenza like disease and other symptoms in the elderly in China.
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<p><b>OBJECTIVE</b>To investigate the features of intelligence development, facial expression recognition ability, and the association between them in children with autism spectrum disorder (ASD).</p><p><b>METHODS</b>A total of 27 ASD children aged 6-16 years (ASD group, full intelligence quotient >70) and age- and gender-matched normally developed children (control group) were enrolled. Wechsler Intelligence Scale for Children Fourth Edition and Chinese Static Facial Expression Photos were used for intelligence evaluation and facial expression recognition test.</p><p><b>RESULTS</b>Compared with the control group, the ASD group had significantly lower scores of full intelligence quotient, verbal comprehension index, perceptual reasoning index (PRI), processing speed index(PSI), and working memory index (WMI) (P<0.05). The ASD group also had a significantly lower overall accuracy rate of facial expression recognition and significantly lower accuracy rates of the recognition of happy, angry, sad, and frightened expressions than the control group (P<0.05). In the ASD group, the overall accuracy rate of facial expression recognition and the accuracy rates of the recognition of happy and frightened expressions were positively correlated with PRI (r=0.415, 0.455, and 0.393 respectively; P<0.05). The accuracy rate of the recognition of angry expression was positively correlated with WMI (r=0.397; P<0.05).</p><p><b>CONCLUSIONS</b>ASD children have delayed intelligence development compared with normally developed children and impaired expression recognition ability. Perceptual reasoning and working memory abilities are positively correlated with expression recognition ability, which suggests that insufficient perceptual reasoning and working memory abilities may be important factors affecting facial expression recognition ability in ASD children.</p>
Subject(s)
Adolescent , Child , Female , Humans , Male , Autism Spectrum Disorder , Psychology , Child Development , Facial Expression , IntelligenceABSTRACT
OBJECTIVES: A modified insulin tolerance test (ITT) can be used to simulate a physiological stress state through the induction of controlled hypoglycemia in healthy volunteers. This allows for evaluation of hypothalamic-pituitary-adrenocortical axis response to stress via a surge in cortical release. However, a consequence of severe, prolonged hypoglycemia is QT interval prolongation. The aim of this analysis was to confirm that blood glucose lowering to 60 mg/dL (previously identified as adequate for inducing stress) has low risk of inducing clinically significant QT prolongation. MATERIALS AND METHODS: Continuous ECG monitoring was conducted as a planned sub study of an open-label, 2-period study involving 18 healthy male subjects. The QTcF response to hypoglycemia was measured over 2 identical periods, ~ 7 days apart. RESULTS: An indirect- response model adequately described the pharmacological relationship between blood glucose and QTcF intervals over the time-course of the ITT. The model correctly identified the steep glucose-QT relationship as an on-off response with a large Hill coefficient of 59 and the threshold glucose, EC50, as ~ 57 mg/dL with narrow between-subject variability of 10%. Simulated QTcF profiles over the course of an ITT did not demonstrate any QTcF interval changes of clinical concern, defined as QTcF observation > 500 ms, if hypoglycemia did not reach below 60 mg/dL. The statistical prediction that the chance of a mean QTcF observation > 500 ms was < 0.0001. CONCLUSIONS: Results support that an ITT maintained at or above 60 mg/dL is unlikely to cause QT prolongation in healthy volunteers and does not warrant continuous ECG monitoring in this group of subjects.
Subject(s)
Arrhythmias, Cardiac/etiology , Blood Glucose/metabolism , Computer Simulation , Diagnostic Techniques, Endocrine , Hypoglycemia/complications , Hypoglycemic Agents , Insulin , Models, Biological , Adult , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/physiopathology , Biomarkers/blood , Electrocardiography , Healthy Volunteers , Humans , Hypoglycemia/blood , Hypoglycemia/diagnosis , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Infusions, Intravenous , Insulin/administration & dosage , Insulin/adverse effects , Male , Predictive Value of Tests , Risk Assessment , Risk Factors , Time FactorsABSTRACT
<p><b>OBJECTIVE</b>This study aimed at evaluating the efficacy and safety of a combination treatment of entecavir and Peginterferon alpha-2a for HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads.</p><p><b>METHODS</b>60 treatment-naive HBeAg-positive CHB patients with high serum hepatitis B viral loads were enrolled and randomly divided into three groups: group A received Peginterferon alpha-2a monotherapy for 48 weeks (n = 20); group B received entecavir monotherapy for more than 48 weeks (n = 20); group C received Peginterferona alpha-2a combined with entecavir for 12 weeks, then Peginterferon alpha-2a monotherapy for 36 weeks (n = 20). Virological response, ALT normalization, HBeAg and HBsAg seroclearance rate were analysed at the end of 4, 12 and 24 weeks after the treatment.</p><p><b>RESULTS</b>The ratio of undetectable hepatitis B virus (HBV) DNA were 50% and 10%, 95% and 25% and 100% and 30% in group C and group A respectively, 50% and 20%, 95% and 75% and 100% and 90% in group C and group B respectively at the end of 4, 12 and 24 weeks of treatment. The differences were significant between group C and A (Z = -4.6, P < 0.001), group C and B (Z = -2.53, P = 0.0114). ALT normalization rate was significantly lower in group A than that of group C (Z = -2.63, P = 0.0086). HBeAg levels declined more in group C than the other two groups after 24 weeks of treatment.</p><p><b>CONCLUSIONS</b>For HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads, combination treament of Peginterferon alpha-2a with entecavir is more effective than Peginterferon alpha-2a monotherapy in virologic response and ALT normalization after 24 weeks of treatment.</p>
Subject(s)
Humans , Alanine Transaminase , Blood , Antiviral Agents , Drug Therapy, Combination , Guanine , Hepatitis B e Antigens , Blood , Hepatitis B, Chronic , Drug Therapy , Virology , Interferon-alpha , Polyethylene Glycols , Recombinant Proteins , Viral LoadABSTRACT
The carotid sinus baroreceptor reflex (CSR) is an important approach for regulating arterial blood pressure homeostasis instantaneously and physiologically. Activation of the central histaminergic or cholinergic systems results in CSR functional inhibitory resetting. However, it is unclear whether two systems at the nucleus tractus solitarius (NTS) level display cross interaction to regulate the CSR or not. In the present study, the left or right carotid sinus region was isolated from the systemic circulation in Sprague-Dawley rats (sinus nerve was reserved) anesthetized with pentobarbital sodium. Respective intubation was conducted into one side isolated carotid sinus and into the femoral artery for recording the intracarotid sinus pressure (ISP) and mean arterial pressure (MAP) simultaneously with pressure transducers connection in vivo. ISP was set at the level of 0 mmHg to eliminate the effect of initial internal pressure of the carotid sinus on the CSR function. To trigger CSR, the ISP was quickly elevated from 0 mmHg to 280 mmHg in a stepwise manner (40 mmHg) which was added at every step for over 4 s, and then ISP returned to 0 mmHg in similar steps. The original data of ISP and corresponding MAP were fitted to a modified logistic equation with five parameters to obtain the ISP-MAP, ISP-Gain relationship curves and the CSR characteristic parameters, which were statistically compared and analyzed separately. Under the precondition of no influence on the basic levels of the artery blood pressure, the effects and potential regulatory mechanism of preceding microinjection with different cholinoceptor antagonists, the selective cholinergic M1 receptor antagonist, i.e., pirenzepine (PRZ), the M2 receptor antagonist, i.e., methoctramine (MTR) or the N1 receptor antagonist, i.e., hexamethonium (HEX) into the NTS on the changes in function of CSR induced by intracerebroventricular injection (i.c.v.) of histamine (HA) in rats were observed. Meanwhile, the actions and possible modulatory mechanism of preceding microinjection with different histaminergic receptor antagonists, the selective histaminergic H1 receptor antagonist, i.e., chlorpheniramine (CHL) or the H2 receptor antagonist, i.e., cimetidine (CIM) into the NTS on the changes in function of CSR resulted from the i.c.v. cholinesterase inhibitor, physostigmine (PHY) were also examined in order to confirm and to analyze effects of cross interaction between central histaminergic and cholinergic systems on CSR. The main results obtained are as follows. (1) Standalone microinjection of different selective cholinergic receptor antagonists (PRZ, MTR or HEX) or different selective histaminergic receptor antagonists (CHL or CIM) into the NTS with each given dose had no effects on the CSR function and on the basic levels of the artery blood pressure, respectively (P > 0.05). (2) The pretreatment of PRZ or MTR into the NTS with each corresponding dose could attenuate CSR resetting resulted from i.c.v. HA in some degrees, which remarkably moved the posterior half range of ISP-MAP relationship curve downwards (P < 0.05), shifted the middle part of ISP-Gain relationship curve upwards (P < 0.05), and increased reflex parameters such as the MAP range and maximum gain (P < 0.05), but decreased parameters such as saturation pressure and intracarotid sinus pressure at maximum gain (P < 0.05). The catabatic effects of pretreatment with MTR into the NTS on CSR resetting induced by i.c.v. HA were more obvious than those with PRZ (P < 0.05), but pretreatment of HEX with given dose into the NTS had no effects on CSR resetting induced by i.c.v. HA (P > 0.05). (3) The effects of pretreatment of CHL or CIM into the NTS with each corresponding dose on CSR resetting made by i.c.v. PHY were similar to those of pretreatment of PRZ or MTR into the NTS on CSR resetting resulted from i.c.v. HA, and the decreasing effects of pretreatment with CHL into the NTS on CSR resetting induced by i.c.v. PHY were more remarkable than those with CIM (P < 0.05). These findings suggest that CSR resetting resulted from either HA or PHY into the lateral ventricle may partly involve the descending histaminergic or cholinergic pathway from the hypothalamus to NTS, which might evoke a cross activation of the cholinergic system in the NTS, via cholinergic M1 and M2 receptors mediation, especially the M2 receptors showing actions, or trigger another cross activation of the histaminergic system in the NTS, by histaminergic H1 and H2 receptors mediation, especially the H1 receptors displaying effects.
Subject(s)
Animals , Rats , Baroreflex , Carotid Sinus , Physiology , Chlorpheniramine , Pharmacology , Cholinergic Antagonists , Pharmacology , Cimetidine , Pharmacology , Histamine , Pharmacology , Pressoreceptors , Physiology , Rats, Sprague-Dawley , Solitary Nucleus , PhysiologyABSTRACT
Our earlier research has shown that mono-substituted N-phenyl-2, 2-dichloroacetamide exhibited much higher anti-cancer activity than the lead compound sodium dichloroacetate (DCA). In this paper, a variety of multi-substituted N-phenyl-2, 2-dichloroacetamides were synthesized and biologically evaluated. The results showed that 3, 5-disubstituted N-phenyl-2, 2-dichloroacetamide analogues had satisfactory potency. Among them, N-(3, 5-diiodophenyl)-2, 2-dichloroacetamide had an IC50 of 2.84 micromol x L(-1) against non-small cell lung cancer cell line A549 and could induce cancer cell apoptosis.
Subject(s)
Humans , Acetamides , Chemistry , Pharmacology , Antineoplastic Agents , Chemistry , Pharmacology , Apoptosis , Carcinoma, Non-Small-Cell Lung , Pathology , Cell Line, Tumor , Drug Design , Inhibitory Concentration 50 , Molecular Structure , Structure-Activity RelationshipABSTRACT
The efficacy of colorectal cancer treatment is not very satisfactory.Conventional morphologic imagings are limited in the diagnosis and in the applications of multimodality treatment for colorectal cancer.18 F-fluorodeoxyglucose PET-CT can play a pivotal role in detecting metabolism changes and in the localization of lesions concurrently.It is valuable in the assessment of responses to therapy,prediction of prognosis and selecting modality management and monitoring postoperative recurrence.The right-moment and proper application of PET-CT can increase the therapeutic efficacy of colorectal cancer.
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<p><b>OBJECTIVE</b>To explore the feasibility and practical value of fluorescence in situ hybridization (FISH) detection of TERC gene amplification in cervical intraepithelial lesions (CIN) and squamous cell carcinoma (SCC).</p><p><b>METHODS</b>Tissue microarray was constructed to cover 150 cases of various cervical conditions, including 24 cases of normal cervical mucosa, 78 cases of CINs (CINI, 25 cases; CINII, 21 cases and CINIII, 32 cases) and 48 cases of SCC. FISH was used to detect TERC gene amplification.</p><p><b>RESULTS</b>TERC gene amplification was detected in 8% (2/25) CINI, 47.6% (10/21) CINII, 71.9% (23/32) CINIII and 87.5% (42/48) SCC. There were significant differences among these groups (P < 0.05). The amplification rates of TERC gene in SCC, CINIII and CINII were significantly higher than those of normal cervical epithelium and CINI (P < 0.05). Significant differences were also observed among CINI and CINII, CINIII and SCC (P < 0.05), and between CINII and SCC (P < 0.05). There were no significant differences between normal cervical epithelium and CINI, CINII and CIN III, and between CINIII and SCC (P > 0.05). FISH detection of amplification of TERC gene in CINI and CINII-III demonstrated the following statistics: sensitivity of 62.3%, specificity of 92.0%, accuracy of 71.8%, positive and negative predictive values of 94.3% and 53.5%, respectively.</p><p><b>CONCLUSIONS</b>FISH detection is a reliable method in detecting TERC gene amplification using paraffin tissue sections. When histological evaluation becomes difficult, TERC amplification detectable by FISH may offer a diagnostic distinction of CINI from CINII. Moreover, TERC amplification may be used as a biomarker in predicting CIN progression to invasive cancer.</p>
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Young Adult , Adenoma , Diagnosis , Genetics , Biomarkers, Tumor , Carcinoma, Squamous Cell , Diagnosis , Genetics , Uterine Cervical Dysplasia , Diagnosis , Genetics , Disease Progression , Gene Amplification , In Situ Hybridization, Fluorescence , RNA , Genetics , Sensitivity and Specificity , Telomerase , Genetics , Uterine Cervical Neoplasms , Diagnosis , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the diagnosis and treatment of macrocystic serous adenoma of the pancreas (MSAP).</p><p><b>METHODS</b>The clinical data of 5 patients with MSAP treated from October 1999 to October 2009 were retrospectively analyzed. There were 5 female and 1 male.</p><p><b>RESULTS</b>Of the 5 patients, 3 patients presented with abdominal pain and fullness, 1 patient with jaundice, 1 patient with asymptomatic. Ultrasonography and CT could manifest macrocystic lesion of the pancreas; all the lesion showed a well-defined border, internal septations, enhanced cyst walls, with no intramural (mural) nodule and papillary projections; the wall was smooth and thin in 4 cases; irregular lobulation could be observed in 3 cases, round or oval in 2 cases; 2 cases had pancreatic duct dilatation, 1 case had biliary duct dilatation. The tumors located in the pancreatic body and tail in 3 cases, the tumors located the pancreatic head in 2 cases. The sizes of the tumors ranged from 6.5 cm to 13.0 cm (mean, 8.8 cm). Five patients all accepted surgical intervention. The main postoperative complication was pancreatic fistula (2 cases); all the fistula was cured. Recurrence or metastasis were not found in 5 patient followed up postoperatively from 8 to 35 months.</p><p><b>CONCLUSIONS</b>MSAP has no specific symptoms. The imaging appearance of MSAP is similar to mucinous cystic neoplasm of the pancreas. The tumor can gradually grow up and produce compression symptoms. MSAP can be cured by complete resection.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Cystadenoma, Serous , Diagnosis , General Surgery , Follow-Up Studies , Pancreatic Neoplasms , Diagnosis , General Surgery , Retrospective StudiesABSTRACT
<p><b>OBJECTIVE</b>To discuss the proper surgical management of pancreatic benign and low-grade malignant potential neoplasm.</p><p><b>METHODS</b>The experience of 72 cases who accepted organ preserving pancreatectomy from January 1990 to May 2010 was analyzed retrospectively. There were 24 male and 48 female, aged from 15 to 68 years with mean age of 46 years. There were 9 cases underwent duodenum-preserving resection of the head of the pancreas, 29 cases underwent spleen-preserving distal pancreatectomy, 11 cases underwent middle segmental pancreatectomy, 23 cases underwent tumor extirpation of huge pancreatic cancer in pancreatic head and body.</p><p><b>RESULTS</b>Pancreatic fistula and biliary fistula in 1 case respectively were cured among who accepted duodenum-preserving resection of the head of the pancreas. Pancreatic fistula was found in 3 cases who accepted spleen-preserving distal pancreatectomy. Pancreaticobiliary anastomotic bleeding in 1 case was cured among who accepted middle segmental pancreatectomy. Pancreatic fistula was found in 5 cases among who accepted tumor extirpation of huge pancreatic cancer in pancreatic head and body, and liver metastasis was found in 3 cases at 6, 12, 16 months after surgery respectively.</p><p><b>CONCLUSIONS</b>Organ preserving pancreatectomy can obviously reduce operative injury to patients, its therapeutic effect is similar to that of classical operation, it is the first option of benign and low-grade malignant potential neoplasm.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Follow-Up Studies , Pancreatectomy , Methods , Pancreatic Neoplasms , General Surgery , Retrospective Studies , Treatment OutcomeABSTRACT
18F-FDG PET-CT is of great significance in non-small cell lung cancer diagnosis, staging, treatment options, efficacy evaluation and prediction of prognosis. But it has non-specificity, and its application is limited. In recent years, a number of new non-18F-FDG imaging agents is constantly developed and used clinically, which contributes to the PET -CT's further development and application in lung cancer.