ABSTRACT
Selective occlusion of tumor vasculature has proven to be an effective strategy for cancer therapy. Among vascular coagulation agents, the extracellular domain of coagulation-inducing protein tissue factor, truncated tissue factor (tTF), is the most widely used. Since the truncated protein exhibits no coagulation activity and is rapidly cleared in the circulation, free tTF cannot be used for cancer treatment on its own but must be combined with other moieties. We here developed a novel, tumor-specific tTF delivery system through coupling tTF with the DNA aptamer, AS1411, which selectively binds to nucleolin receptors overexpressing on the surface of tumor vascular endothelial cells and is specifically cytotoxic to target cells. Systemic administration of the tTF-AS1411 conjugates into tumor-bearing animals induced intravascular thrombosis solely in tumors, thus reducing tumor blood supply and inducing tumor necrosis without apparent side effects. This conjugate represents a uniquely attractive candidate for the clinical translation of vessel occlusion agent for cancer therapy.
ABSTRACT
MAMLD1 gene has been implicated in 46,XY disorders of sex development (DSD) in recent years. Patients carrying MAMLD1 gene variants showed a "continuous spectrum" of simple micropenis, mild, moderate and severe hypospadias with micropenis, cryptorchidism, split scrotum and even complete gonadal dysplasia. The function of MAMLD1 gene in sexual development has not been fully elucidated, and its role in DSD has remained controversial. This article has reviewed recent findings on the role of the MAMLD1 gene in DSD, including the MAMLD1 gene, its encoded protein, genetic variants, clinical phenotype and possible pathogenic mechanism in DSD.
Subject(s)
Humans , Male , DNA-Binding Proteins/genetics , Disorders of Sex Development/genetics , Mutation , Nuclear Proteins/genetics , Phenotype , Sexual Development , Transcription Factors/geneticsABSTRACT
Objective:To evaluate the efficacy and mechanism of continuous blood purification(CBP) in the treatment of severe sepsis in children.Methods:A total of 42 patients with severe sepsis were enrolled in the study.According to the parents undefined desire to treatment, on the basis of the same treatment condition, 30 cases in the blood purification group were treated with CBP, and 12 cases in the control group were given the routine treatment without CBP treatment.The difference of each index between the two groups at the baseline(before treatment) and 72 hours after treatment were observed.Results:The differences of heart rate, mean arterial pressure and brain natriuretic peptide before and after treatment in the blood purification group were significantly higher than those in control group( P<0.05), and the differences of oxygenation index, 24-hour average urine volume, blood urea nitrogen, creatinine and Glasgow coma score in the blood purification group were significantly higher than those in control group( P<0.05). The difference of capillary refill time, lactic acid and central venous oxygen saturation in blood purification group were significantly higher than those in control group( P<0.05). The level of white blood cell count, C-reactive protein, procalcitonin and interleukin-6 in blood purification group were significantly higher than those in control group, with all significant difference( P<0.05). There was significant difference in critical illness score between two groups after treatment and before treatment.The mortality rate of the blood purification group was significantly lower than that in control group( P<0.01). Conclusion:CBP can improve cardiovascular function, brain function, renal function, tissue perfusion, inflammation index, internal environment, and improve the score of children with severe sepsis.
ABSTRACT
Congenital hyperinsulinism (CHI) is the most frequent cause of persistent hypoglycemia in infancy,and it is a rare genetic disorder characterized by severe hypoglycemia caused by inappropriate insulin secretion by pancreatic β-cells.The clinical presentation,histology,genetics and response to medical treatment are of genetic heterogeneity.Appropriate treatment is critically important as profound and repeated episodes of hypoglycemia often cause severe brain damage.Based on the biochemical profiles,clinical diagnosis is relative easier to be established,however,the genetic basis is only found in approximately 45％-55％ of patients.In terms of treatment,Diazoxide is recommended as first-line treatment for all patients [5-20 mg/(kg · d)].In patients unresponsive to Diazoxide,if genetic result confirms a monoallelic,recessive paternally-inherited mutation in ABCC8 or KCNJ11,and 18F-fluorodihydroxyphenylalanine-positron emission tomography-computed tomography scan indicates the lesion is located in the body or tail of the pancreas,surgical treatment is recommended.And for the other patients,subcutaneous octreotide,intravenous glucagon,or oral calcium antagonist should be sequentially attempted in order to minimize the need for near-total/subtotal pancreatectomy.
ABSTRACT
Objective To investigate the characteristics of peroperative blood pressure and heart rate in patients with normotensive incidental pheochromocytomas in order to provide the basis for peroperative treatment. Methods This retrospective study collected the data of 104 patients with a pathological diagnosis of unilateral pheochromocytoma at PLA General Hospital during January 2011 to December 2016. They were divided into normotensive incidental pheochromocytomas(NIP) group (n＝50) if the patients were normotensive and HIP group ( n＝54) if the patients were with hypertension. The clinical features, imaging features and peroperative hemodynamics were analyzed. Results ( 1) The age, urinary norepinephrine, daily dosage and duration of phenoxybenzamine in NIP group were less than those of HIP group (all P<0.05). (2) Preinduction blood pressure, maximum blood pressure, and total fluid intake in NIP group were lower than those in HIP group(all P<0.05). The blood pressure range, heart rate range, increased blood pressure, minimum mean arterial pressure, vasoactive medication were without statistical significance between these two groups. ( 3) The times and rate of intraoperative systolic blood pressure more than 30% baseline, 200 mmHg (1 mmHg＝0.133 kPa), 180 mmHg, 160 mmHg, intraoperative tachycardia, bradycardia, intraoperative hypotension and postoperative hypotension were without statistical significance between these two groups. (4) Stratified analysis of age (50 years), phenoxybenzamine (40 mg/d), tumor diameter (50 mm) and preinduction blood pressure (130/80 mmHg) showed that intraoperative blood pressure and heart rate were without statistical significance between these two groups. ( 5) There was no correlation between phenoxybenzamine ( daily dosage or duration ) and peroperative hypotension. Applying phenoxybenzamine or vasoactive medication was not correlated with peroperative hypotension in NIP group. Conclusion The peroperative blood pressure and heart rate of patients with NIP are similar to those of patients with HIP. Adequate peroperative treatment should be applied to NIP to avoid hemodynamic instability.
ABSTRACT
Objective To summarize and analyze the clinical features and etiologies in hospitalized patients with syndrome of inappropriate antidiuretics (SIAD) during the past 25 years.Methods All data of 128 patients with SIAD admitted to Chinese PLA General Hospital since January 1991 to January 2016 were collected.SIAD was diagnosed based on the 1957 criterion.Results (1) The most frequent causes of increased inappropriate secretion of vasopressin were malignant tumors , lung diseases ( e.g.pneumonia ) , and central nervous system diseases , in which malignant tumors accounted for 38.28% of the SIAD.(2) During the past 25 years, the proportion of malignant diseases declined from 4/7 to 35.29%, while, the proportion of pulmonary infection increased from 1/7 to 35.29% ( P<0.05 ) .( 3 ) The patients with malignant tumors had the lowest serum sodium and serum osmolality among all SIAD patients .(4) CT scan had a high diagnostic value for chest and brain detection .( 5 ) Among three SIAD subjects with unknown reasons at onset , two were diagnosed with small cell lung cancer and one with gastric cancer during follow -up.Conclusion The etiology of SIAD is complex and it could be attributed to multifarious etiological factors.Malignant tumors account for the largest proportion of all patients , and pulmonary infection was ranked in second place .Cautions on tumors have to be taken when serum sodium of a SIAD patient is below 118.1 mmol/L.
ABSTRACT
Objective To analyze the relationship between the brain functional alterations of patients with Cushing's disease (CD) and patients' mental symptom by applying the Evaluating Emotional Scales and task functional magnetic resonance imaging (Task fMRI).Methods Task fMRI was performed on 8 patients with diagnosed CD admitted in the Department of Endocrinology of Chinese PLA General Hospital from Nov. 2015 to Nov. 2016 and 21 healthy people with matched age, gender and education level as control. Meanwhile, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Positive and Negative Affective Scale (PANAS) and Cushing Quality of Life Scale (Cushing QOL) were obtained to assess the brain functions.Results Significant depression and anxiety were observed in patients with CD, and their positive affective score was substantially lower while the negative affective score was relatively higher compared with that in the controls. Task fMRI revealed that, when watching the positive pictures, the activation degree of left cerebellum and right postcentral gyrus weakened in CD patients than in the controls, and the positive correlations existed between the activation degree of left cerebellum and the 16 o'clock adrenocorticotrophic hormone (ACTH) level, and between the activation degree of right postcentral gyrus and the urinary free cortisol (UFC) level in CD patients. In contrast, when watching the negative pictures, the activation degree of left cerebellum, bilateral parahippocampal gyrus and left inferior frontal gyrus was weakened in CD patients than in the controls, and the activation degree of left cerebellum was negatively correlated to the 0 o'clock cortisol level and SAS score, but is positively correlated to the UFC level. When watching the neutral pictures, the activation degree of left cerebellum and left parahippocampal gyrus was weakened in CD patients than in the controls.Conclusions CD patients may have impaired brain function with depression and anxiety mental symptoms. By Task fMRI, it can be found that the weakened activation degree of left inferior frontal gyrus, right postcentral gyrus, bilateral parahippocampal gyrus and left cerebellum may be related to CD patients' mental symptoms.
ABSTRACT
Objective To evaluate the clinical characteristics of patients with growth-hormone adenoma (GHA) and summarize the diagnosis and treatment experience.Methods The clinical data of 338 GHA cases at the General Hospital of PLA from Jan. 1990 to Dec. 2016 were collected, of which 252 cases with more complete clinical data were retrospectively analyzed including their general situation, medical history, laboratory tests and auxiliary examinations, and treatment modalities and outcomes. Parts of the patients were followed up.Results The cases of hospitalized GHA patients have increased year by year since 1990, and the number of patients admitted in the last 3 years accounted for 56.2% of the total number of cases. The sex ratio for GHA patients was nearly 1:1. Age of visiting followed Gaussian distribution while the 41-50 age group occupied the largest part. The most typical sign is hand and foot enlargement (60.7%), followed by the hypertrophy of nasal ala. The most common symptoms are headache (42.5%), hypopsia, visual field defect and diplopia. More than half of GHA patients were complicated with prediabetes and diabetes (72.6%), sleep apnea (69.5%), goiter or thyroid nodularity (56.4%), cardiac insufficiency (57.0%) and colon polyp (54.1%); while the percentages of cases undergone the relevant examination in the total number of cases were as follows: 75g OGTT test (42.1%), polysomnography (23.4%), thyroid ultrasound (37.3%), echocardiogram (47.6%) and colonoscopy (14.7%); GHA was 23.37±1.42μg/L and IGF-1 was 804.28±273.93ng/ml on average; 85.0% of somatotroph tumors are macroadenoma. Surgery remains the mainstay of therapy to GHA, while medical therapy was selected by less patients. During the follow-up, only 38.0%of GHA patients can be contacted, among them the remission rate decreased to 40.5%. The positive rate of long-term remission evaluated by early postoperative GHA level was consistent with that confirmed by the long-term follow-up (χ2=3.368,P>0.05). Conclusions The number of hospitalized GHA patients have increased recent years. The common clinical signs and symptoms are somatic enlargement and nonspecific headache. Due to uncompleted screening, GHA associated complications are always misdiagnosed; It is essential to establish a sound model of follow-up to improve patients' quality of life. The early postoperative GHA levels may predict the prognosis of surgery.
ABSTRACT
Disorders of sex development (DSD) are a wide range of conditions with diverse features and pathophysiology.These clinical situations can often be difficult to classify,diagnose and treat,particularly in 46,XY DSD cases.A comprehensive differential diagnosis should be based on detailed evaluation of the genitalia,imaging and hormone investigations,as well as the genetics analysis.To achieve a better prognosis,the gonadal function needs to be protected as far as possible in the treatment of choice.As for the adolescent boys with congenital hypogonadotropic hypogonadodism,pulsatile gonadotrophin releasing hormone is superior to human chorionic gonadotrophin in therapeutic efficacy in the induction of puberty,and the latter could considered as an alterative,the course of treatment should be kept for 1 year.In this article,the literatures in this field are reviewed,combined with clinical practice experience from National Center for Children's Health to establish a framework that could assist clinicians to make better diagnosis and treatment decisions for 46,XY DSD.
ABSTRACT
[Summary] Over the past year, researches in the field of gonadal diseases have achieved rapid advances. Considerable literatures concerning the diagnosis and treatment of these diseases have been published. We herely reviewed and analyzed literatures which may be helpful to clinical practice in the future, while the defects and deficiencies in this field in China were also discussed with some suggestions proposed for the future.
ABSTRACT
<p><b>OBJECTIVE</b>To construct an effective system screening and evaluating possible injections and components inducing allergy type II.</p><p><b>METHOD</b>Transfect IgG promoter-regulated green fluorescent protein expressing plasmid into RPMI-8226 cell. The number of fluorescent cells after drug treatment was calculated and statistically evaluated.</p><p><b>RESULT</b>Tween 80 can suppress the expression of IgG effectively, and puerarin has activity of stimulating IgG expression, and the system has no response to KCl-treatment. No effect of Yuxingcao (Herba Houttuyniae) injection on this system is observed.</p><p><b>CONCLUSION</b>IgG promoter-drove green fluorescent protein expressing cell line can be used as system screening injections and components inducing allergy type II based on stimulating IgG promoter activity. Tween 80 can suppress the expression of IgG at the transcriptional level. Four batches of Yuxingcao injection cannot induce allergy type II by activating IgG expression.</p>
Subject(s)
Humans , Male , Cell Line, Tumor , Gene Expression , Green Fluorescent Proteins , Genetics , Metabolism , Immunoglobulin G , Genetics , Injections , Plant Extracts , Pharmacology , Plants, Medicinal , Chemistry , Plasmids , Genetics , Promoter Regions, Genetic , GeneticsABSTRACT
There is a very complicated electrolytical environment in oral cavity with plenty of microorganisms existing there. Various forms of corrosion would develop when metallic prosthesis functions in mouth. One important corrosive form is microbial corrosion. The metabolic products, including organic acid and inorganic acid, will affect the pH of the surface or interface of metallic prosthesis and make a change in composition of the medium, thus influencing the electron-chemical reaction and promoting the development of corrosion. The problem of develpoment of microbial corrosion on dental alloy in the oral environment lies in the primary condition that the bacteria adhere to the surface of alloy and form a relatively independent environment that promotes corrosion.