ABSTRACT
In view of the recent advancements in the standardized neurology residency training in China, standardized neurology fellowship training has become a crucial next step for China′s graduate medical education. The design of the fellowship and development of relevant norms and standards to ensure quality training constitute key areas in need of further consideration. The United States has established a standardized neurology fellowship training for nearly 30 years and has been successful in ensuring high quality physician training. Currently there are 9 accreditation council for graduate medical education (ACGME) accredited neurology fellowship programs in the USA, including clinical neurophysiology, pain medicine, neurodevelopmental disabilities, vascular neurology, neuromuscular medicine, sleep medicine, endovascular surgical neuroradiology, epilepsy and brain injury medicine. Among them, the number of fellowship training programs in vascular neurology, clinical neurophysiology, and epilepsy are relatively stable or show continuous growth, while neurodevelopmental disabilities and brain injury medicine remain stagnant or even retrogressive. It indicates that design of the neurology fellowship training calls for full weight of a wide array of factors, taking into account the number of subspecialty patients, clinical applications, prospects for future development of the subspecialties, and lessons learned from the United States. We can start with ACGME accredited steady growth fellowship programs and then add others in the future accordingly.
ABSTRACT
In view of the recent advancements in the standardized neurology residency training in China, standardized neurology fellowship training has become a crucial next step for China′s graduate medical education. The design of the fellowship and development of relevant norms and standards to ensure quality training constitute key areas in need of further consideration. The United States has established a standardized neurology fellowship training for nearly 30 years and has been successful in ensuring high quality physician training. Currently there are 9 accreditation council for graduate medical education (ACGME) accredited neurology fellowship programs in the USA, including clinical neurophysiology, pain medicine, neurodevelopmental disabilities, vascular neurology, neuromuscular medicine, sleep medicine, endovascular surgical neuroradiology, epilepsy and brain injury medicine. Among them, the number of fellowship training programs in vascular neurology, clinical neurophysiology, and epilepsy are relatively stable or show continuous growth, while neurodevelopmental disabilities and brain injury medicine remain stagnant or even retrogressive. It indicates that design of the neurology fellowship training calls for full weight of a wide array of factors, taking into account the number of subspecialty patients, clinical applications, prospects for future development of the subspecialties, and lessons learned from the United States. We can start with ACGME accredited steady growth fellowship programs and then add others in the future accordingly.
ABSTRACT
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
<p><b>OBJECTIVE</b>To further investigate the risk factors of cubitus varus in humeral condylar fracture after conservative treatment in children through Logistic regression analysis, so as to guide the clinical treatment.</p><p><b>METHODS</b>Children with humeral condylar fracture who were treated by manipulative reduction and plaster fixation in our hospital from March 2008 to December 2014 were studied. The clinical data including age, gender, BMI, time from injury to reduction, direction of displacement, rotation displacement, fixed position, and epiphyseal injury were collected. First, preliminary screen the risk factors through univariate analysis of the above data, then determine the risk factors of cubitus varus through multivariate Logistic regression analysis of the significant factors from univariate analysis.</p><p><b>RESULTS</b>Univariate analysis showed that time from injury to reduction, direction of displacement, rotation displacement and epiphyseal injury were significantly correlated with the cubitus varus. Multivariate Logistic regression analysis showed that time from injury to reduction which was longer than 8 h [=0.017, OR=3.303(1.243-8.774)], ulnar displacement [=0.001,=11.951(2.895-49.335)], rotation displacement [=0.003, OR=4.190(1.643-10.685)]and epiphyseal injury [=0.000,=7.092(2.557-19.671)] were independent risk factors of cubitus varus.</p><p><b>CONCLUSIONS</b>Time from injury to reduction, ulnar displacement, rotation displacement and epiphyseal injury are independent risk factors of cubitus varus. So it need corresponding treatment according to different risk factors.</p>
ABSTRACT
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.
Subject(s)
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 develop a better method for preparation of porcine model of acute myocardial infarction by permanent occlusion of the left circumflex coronary artery and minimally invasive surgery, evaluate its validity and stability, and explore its application in experimental studies of ischemic heart diseases.Methods 25 healthy female 3-month-old Bama minipigs, body weight 25±3 kg, were used in this study.The porcine model of myocardial infarction was established by minimally invasive surgery and the left circumflex artery ligation at the site of OM1 posterior position under general anesthesia.Heart function was assessed by echocardiography at 15 min before surgery, 1 hour and 4 weeks after surgery.Pathological examination was performed at 4 weeks after the left circumflex artery occlusion.The mortality and cause of death were statistically analyzed.Results The 1-hour and 4-week postoperative cardiac function was considerably decreased, showing a decreased ejection fraction from 64.2±4.6% to 48.2±5.3% (1hour after MI) and 49.7±6.1% (4 weeks after MI) (P<0.01).Pathological examination revealed that the ventricular wall was thinner and the amount of collagens was increased in the infracted area.The ventricular fibrillation rate at 1-hour after myocardial infarction was 17.3% and the infarction area was 19.2%.Conclusions A pig model of acute myocardial infarction can be prepared by our modified left circumflex coronary artery ligation at the obtuse marginal artery (OM1) and minimally invasive surgery.This model exhibits advantages such as minimal surgical trauma, high stability of the model, and low mortality, therefore, provides an ideal and economic animal model for experimental studies on acute ischemic heart diseases.
ABSTRACT
The aim of this study was to determine the effect of dexamethasone (DEX) on renal ischemia/reperfusion injury (IRI). C57BL/6 mice were randomly divided into Sham group, IRI group and DEX group. The mice in IRI and DEX groups subjected to renal ischemia for 60 min, were treated with saline or DEX (4 mg/kg, i.p.) 60 min prior to I/R. After 24 h of reperfusion, the renal function, renal pathological changes, activation of extracellular signal-regulated kinase (ERK) and glucocorticoid receptor (GR), and the levels of iNOS and eNOS were detected. The results showed DEX significantly decreased the damage to renal function and pathological changes after renal IRI. Pre-treatment with DEX reduced ERK activation and down-regulated the level of iNOS, whereas up-regulated the level of eNOS after renal IRI. DEX could further promote the activation of GR. These findings indicated GR activation confers preconditioning-like protection against acute IRI partially by up-regulating the ratio of eNOS/iNOS.
Subject(s)
Animals , Male , Mice , Dexamethasone , Pharmacology , Gene Expression Regulation, Enzymologic , Glucocorticoids , Pharmacology , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Receptors, Glucocorticoid , Reperfusion Injury , Pathology , Up-RegulationABSTRACT
The aim of this study was to determine the effect of dexamethasone (DEX) on renal ischemia/reperfusion injury (IRI). C57BL/6 mice were randomly divided into Sham group, IRI group and DEX group. The mice in IRI and DEX groups subjected to renal ischemia for 60 min, were treated with saline or DEX (4 mg/kg, i.p.) 60 min prior to I/R. After 24 h of reperfusion, the renal function, renal pathological changes, activation of extracellular signal-regulated kinase (ERK) and glucocorticoid receptor (GR), and the levels of iNOS and eNOS were detected. The results showed DEX significantly decreased the damage to renal function and pathological changes after renal IRI. Pre-treatment with DEX reduced ERK activation and down-regulated the level of iNOS, whereas up-regulated the level of eNOS after renal IRI. DEX could further promote the activation of GR. These findings indicated GR activation confers preconditioning-like protection against acute IRI partially by up-regulating the ratio of eNOS/iNOS.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the relationship between the colonization of group B streptococci (GBS), mycoplasma,and Chlamydia trachomatis (CT) infections and spontaneous abortion due to early embryonic death.</p><p><b>METHODS</b>Totally 74 patients (study group) who experienced the missed abortion during their first or second trimester and 62 women (control group) who underwent induced termination of normal pregnancy during the first or second trimester were enrolled in this study. The vaginal secretions, intrauterine aspirates, and amniotic fluids were collected for GBS culture. Cervical mycoplasma (UU+MH) and CT were detected at the same time.</p><p><b>RESULTS</b>Positive results of GBS culture of vaginal secretions were detected in 9 patients (12.16%) in the study group, but in only 6 patients (9.68%) in control group (P=0.662). The intrauterine aspirate samples (as well as the amniotic fluid samples) of all cases were negative in GBS culture. The positive rates of UU and MH were 32.43% (24/74) and 16.22% (12/74) in the study group, but were only 10.35% (12/62) (P=0.0103) and 6.45 (4/62) (P=0.042) in the control group. The positive rate of CT was 8.11% (6/74) in the study group and 8.06 % (5/62) in the control group (P=0.905). The rate of concurrent infection of GBS and mycoplasma was 4.05% (3/74) in the study group and 6.45% (4/62) in the control group (P=0.743). The rate of concurrent infection of GBS and CT was 0 in the study group and 1.61% (1/62) in the control group (P=0.475). The rate of concurrent mycoplasma and CT infection was 2.70% (2/74) in the study group and 0 in the control group (P=0.325). Furthermore, no one was positive for poly infection of all these three pathogens.</p><p><b>CONCLUSIONS</b>GBS may be positive in the genital tract of some pregnant women but is not related with early abortion. The mycoplasma infection may be one of the reasons leading to arrested intrauterine pregnancy.</p>