Search

Hepatic venous pressure gradient measurement via jugular vein catheterization is still currently the gold standard for evaluating portal hypertension. However, how to accurately and reproducibly assess whether there is portal hypertension has always been a concern in patients with liver cirrhosis. In recent years, imaging methods have made significant progress in the non-invasive diagnosis of portal hypertension. This paper reviews the current different diagnostic value of imaging methods and related research progress in an attempt to evaluate patients with cirrhotic portal hypertension.目前经颈静脉插管测量肝静脉压力梯度仍是评价门静脉高压的金标准，如何准确、可重复地无创评估肝硬化患者是否存在门静脉高压，一直备受关注。近年来，影像学方法无创诊断门静脉高压取得重要进展，现就不同影像方法在评价肝硬化患者门静脉高压的诊断价值及相关研究进展予以综述。.

原发于子宫的脂肪肉瘤罕见，该文报道1例原发于子宫、去分化成分与高分化脂肪肉瘤两种成分混杂生长的去分化脂肪肉瘤。该例发生于罕见部位子宫体，肿瘤的组织学生长模式亦为不常见模式，间质黏液样变，所以容易误导影像学诊断，而对子宫的活检和诊刮，病理学诊断亦具有一定挑战性。.

BACKGROUND The aim of this study was to evaluate the dispersal effects of 3,5-dicaffeoylquinic acid (3,5-DCQA) against the preformed biofilm of Aspergillus fumigatus and to investigate its potential mechanism. MATERIAL AND METHODS Aspergillus fumigatus biofilms of laboratory strain AF293 and clinical strain GXMU04 were generated in 24- or 96-well polystyrene microtiter plates in vitro. Crystal violet assay and XTT reduction assay were performed to evaluate the effects of 3,5-DCQA on biofilm biomass, extracellular matrix, and metabolic activity alteration of cells in biofilms. Real-time PCR was performed to quantify the expression of hydrophobin genes. The cytotoxicity of 3,5-DCQA on human erythrocytes was evaluated by a hemolytic assay. RESULTS The results indicated that 3,5-DCQA in subminimum inhibitory concentrations (256 to 1024 mg/L) elicited optimal A. fumigatus biofilm dispersion activity and improved the efficacy of VRC and AMB in minimal fungicidal concentrations (MFCs) to combat fungal cells embedded in biofilms. The results of scanning electron microscope (SEM) and confocal laser scanning microscopy (CLSM) revealed 3,5-DCQA facilitated the entry of antifungal agents into the A. fumigatus biofilm through eliminating the hydrophobic extracellular matrix (ECM) without affecting fungal growth. Real-time PCR indicated that 3,5-DCQA down-regulated the expression of hydrophobin genes. Hemolytic assay confirmed that 3,5-DCQA exhibited a low cytotoxicity against human erythrocytes. CONCLUSIONS Subminimum inhibitory concentrations of 3,5-DCQA can disperse A. fumigatus biofilm and enhance fungicidal efficacy of VRC and AMB through down-regulating expression of the hydrophobin genes. The study indicated the anti-biofilm potential of 3,5-DCQA for the management of A. fumigatus biofilm-associated infection.

Previous reports show increased incidence of venous thromboembolism [VTE, deep-vein thrombosis (DVT) and pulmonary embolus (PE)] in sickle cell disease (SCD) patients but did not account for frequency of hospitalization. We determined the incidence of VTE in a SCD cohort versus matched controls. For SCD patients, risk factors for incident VTE, recurrence and the impact on mortality were also determined. Among 6237 patients with SCD, 696 patients (11·2%) developed incident-VTE: 358 (51·6%) had PE (±DVT); 179 (25·7%) had lower-extremity DVT only and 158 (22·7%) had upper-extremity DVT. By 40 years of age, the cumulative incidence of VTE was 17·1% for severe SCD patients (hospitalized ≥3 times a year) versus 8·0% for the matched asthma controls. Amongst SCD patients, women (Hazard ratio [HR] = 1·22; 95% confidence interval [CI]: 1·05-1·43) and those with severe disease (HR = 2·86; 95% CI: 2·42-3·37) had an increased risk of VTE. Five-year recurrence was 36·8% in patients with severe SCD. VTE was associated with increased risk of death (HR = 2·88, 95% CI: 2·35-3·52). In this population-based study, the incidence of VTE was higher in SCD patients than matched controls and was associated with increased mortality. The high incidence of recurrent VTE in patients with severe SCD suggests that extended anticoagulation may be indicated.

The incidence of oropharyngeal cancer induced by human papillomavirus (HPV) infection is steadily increasing in developed countries. These tumors are more chemoradiosensitive and have a better prognosis than HPV-negative one. In addition, they occur in younger and better-off patients with longer life expectancy. Current radiotherapy and chemotherapy protocols are currently being questioned as they may expose HPV-positive patients to excessive treatment and unnecessary toxic effects. Less intensive treatment regimens could possibly achieve similar efficacy with lower toxicity and improved quality of life. The aim of this work was to summarize the knowledge on these tumors and their implications for radiation oncologists. In this update, we will discuss ongoing de-escalation trials and highlight the issues raised by these studies. We will also comment on the results of recently published de-intensification studies. Three main strategies are analyzed in the present article: the de-escalation of the drug associated with radiotherapy, the de-escalation of the radiotherapy dose (in concomitant chemoradiotherapy, after induction chemotherapy, in a postoperative setting) and de-escalation of radiation target volumes. Our findings ultimately indicate that clinicians should not change the management of oropharyngeal cancer patients outside of clinical trials.

The prevalence of child and adolescent growth and mental-behavior related diseases are increasing, and the pathogenesis are complex. Twins are excellent natural resources for complex chronic diseases research as they share the maternal intrauterine environment, born at the same time and share the same family environment in early years, which could benefit the adjust ment of confounding factors, such as age, genetic factors and early family environmental factors. Birth cohort with twin families involved could be more effective in exploring the genetic and environmental factors for complex chronic diseases at the very beginning of life. This paper summarizes the objective, content, progress, strengths and potential problems of Wuhan Twin Birth Cohort, with emphasis on the overall design and progress of the study.儿童及青少年期生长发育及心理行为相关疾病患病率有逐年上升趋势，且病因复杂。双生子共享母体宫内环境、同时出生并享有相同的早期家庭环境，能控制年龄、遗传和早期家庭环境等的干扰，是开展复杂慢性疾病研究的良好资源。利用双生子家庭开展出生队列研究，能更好地结合遗传和环境因素寻找复杂慢性疾病的病因起源。本研究从研究目标、内容、进展和优势与潜在问题等方面对武汉双生子出生队列进行简要介绍，着重呈现本研究的总体设计和进展概况。.

The endoplasmic reticulum(ER) is crucial for protein and lipid synthesis, folding and cellular homeostasis. Function impairment of ER would induce ER stress, which might play an important role in many different pathological states. Small heat shock proteins (sHsps) are known to be widely expressed throughout many tissues. SHsps are found to regulate many different pathological and pathophysiological processes and they are supposed to be potential therapeutic targets. Recent studies indicate that multiple sHsps localize to the mammalian and plant ER and sHsps confer protection against ER stress in multiple cellular processes. The mechanisms responsible for the cytoprotective effects of sHsps are related to maintaining ER homeostasis. Improved understanding of sHsps-related cytoprotective action on ER and successful strategies which could specifically target components of ER stress signalling responses amelioration of their toxic effects by sHsps is of great importance in the development of therapeutic approach for the disorders induced by dysfunction of ER.

The enhanced green fluorescent protein (EGFP) pEGFP-N1-P53 eukaryotic expression vector, which contains the human tumor suppressor p53, was constructed and transfected into chicken fibroblast cells and stage-X blastoderm to analyze the transfection efficiency. The complementary DNA of the human p53 gene was cloned by reverse transcription-polymerase chain reaction from human peripheral blood and inserted into the pEGFP-N1 vector by HindIII and BamHI double digestion. The pEGFP-N1-P53 vector was transfected into chicken embryo fibroblasts by Lipofectamine 2000 liposomes, and the transfection efficiency was analyzed by fluorescence microscope after 36 h of transfection. The stage-X blastoderm was also transfected by blastoderm injection using Lipofectamine 2000 liposomes at room temperature after 12-24 h; then hatching occurred until seventh day, and the transfection efficiency was analyzed by fluorescence microscope in the dead embryo. A total of 90 hatching eggs were transfected by the pEGFP-N1-P53 vector, and 20 chicken embryos expressed the reporter gene, which indicated that recombinant pEGFP-N1-P53 could be transfected and expressed in stage-X blastoderm by liposomes. Chicken embryo fibroblasts were transfected and expressed the reporter gene. The pEGFP-N1-P53 vector was constructed successfully and could be transfected and expressed in chicken embryo fibroblasts and stage-X blastoderms efficiently.

It is rare for a study to address immediate metabolic change in pre-eclamptic pregnancy. Our aim is to study the ante-partum and post-partum metabolic markers in pre-eclampsia. A total of 33 pre-eclamptic and 200 uncomplicated women with singleton pregnancies were recruited for the prospective research. Immediately ante-partum and 24–48 h postpartum venous blood samples were collected for the analysis of metabolic markers. In the pre-eclamptic group, the ante-partum fasting glucose, fasting insulin, triglyceride and free fatty acid levels were found to be higher than in the control group; however, ante-partum high-density lipoprotein level was lower. Interestingly, fasting glucose and insulin levels decreased by 24–48 h post-partum in both groups and no significant differences were found. Pre-eclamptic patients had lower post-partum high-density lipoprotein (P=0.02), higher triglyceride (P

Nonspecific building-related symptoms among occupants of modern office buildings worldwide are common and may be associated with important reductions in work performance, but their etiology remains uncertain. Characteristics of heating, ventilating, and air-conditioning (HVAC) systems in office buildings that increase risk of indoor contaminants or reduce effectiveness of ventilation may cause adverse exposures and subsequent increase in these symptoms among occupants. We analyzed data collected by the U.S. EPA from a representative sample of 100 large U.S. office buildings--the Building Assessment and Survey Evaluation (BASE) study--using multivariate logistic regression models with generalized estimating equations adjusted for potential personal and building confounders. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between seven building-related symptom outcomes and selected HVAC system characteristics. Among factors of HVAC design or configuration: Outdoor air intakes less than 60 m above the ground were associated with approximately doubled odds of most symptoms assessed. Sealed (non-operable) windows were associated with increases in skin and eye symptoms (ORs= 1.9, 1.3, respectively). Outdoor air intake without an intake fan was associated with an increase in eye symptoms (OR=1.7). Local cooling coils were associated with increased headache (OR=1.5). Among factors of HVAC condition, maintenance, or operation: the more » presence of humidification systems in good condition was associated with an increase in headache (OR=1.4), whereas the presence of humidification systems in poor condition was associated with increases in fatigue/difficulty concentrating, as well as upper respiratory symptoms (ORs=1.8, 1.5). No regularly scheduled inspections for HVAC components was associated with increased eye symptoms, cough and upper respiratory symptoms (ORs=2.2, 1.6, 1.5). Less frequent cleaning of cooling coils or drip pans was associated with increased headache (OR=1.6). Fair or poor condition of duct liner was associated with increased upper respiratory symptoms (OR=1.4). Most of the many potential risk factors assessed here had not been investigated previously, and associations found with single symptoms may have been by chance, including several associations that were the reverse of expected. Risk factors newly identified in these analyses that deserve attention include outdoor air intakes less than 60 m above the ground, lack of operable windows, poorly maintained humidification systems, and lack of scheduled inspection for HVAC systems. Infrequent cleaning of cooling coils and drain pans were associated with increases in several symptoms in these as well as prior analyses of BASE data. Replication of these findings is needed, using more objective measurements of both exposure and health response. Confirmation of the specific HVAC factors responsible for increased symptoms in buildings, and development of prevention strategies could have major public health and economic benefits worldwide. « less

Breast carcinoma is the most common female cancer with considerable metastatic potential. Signal transducers and activators of the transcription 3 (Stat3) signaling pathway is constitutively activated in many cancers including breast cancer and has been validated as a novel potential anticancer target. Here, we reported our finding with nifuroxazide, an antidiarrheal agent identified as a potent inhibitor of Stat3. The potency of nifuroxazide on breast cancer was assessed in vitro and in vivo. In this investigation, we found that nifuroxazide decreased the viability of three breast cancer cell lines and induced apoptosis of cancer cells in a dose-dependent manner. In addition, western blot analysis demonstrated that the occurrence of its apoptosis was associated with activation of cleaved caspases-3 and Bax, downregulation of Bcl-2. Moreover, nifuroxazide markedly blocked cancer cell migration and invasion, and the reduction of phosphorylated-Stat3Tyr705, matrix metalloproteinase (MMP) MMP-2 and MMP-9 expression were also observed. Furthermore, in our animal experiments, intraperitoneal administration of 50 mg/kg/day nifuroxazide suppressed 4T1 tumor growth and blocked formation of pulmonary metastases without detectable toxicity. Meanwhile, histological and immunohistochemical analyses revealed a decrease in Ki-67-positive cells, MMP-9-positive cells and an increase in cleaved caspase-3-positive cells upon nifuroxazide. Notably, nifuroxazide reduced the number of myeloid-derived suppressor cell in the lung. Our data indicated that nifuroxazide may potentially be a therapeutic agent for growth and metastasis of breast cancer.

Statins are commonly prescribed lipid-lowering medications that significantly reduce the risk of cardiovascular events. In addition to their ability to lower cholesterol by affecting the rate-limiting step in cholesterol biosynthesis, statins also have anti-inflammatory, immunomodulatory, antioxidant, antiapoptotic, and antiplatelet effects. Because of these pleiotropic abilities, statins may have some beneficial effects on neurologic diseases, including cerebrovascular disease, neurodegenerative disease, multiple sclerosis, and brain tumors. Although statins are a well-tolerated class of drugs, they also have potential adverse effects (AEs). A growing body of evidence indicates that statins may have potential negative effects on nervous system-associated diseases, including myopathies, peripheral neuropathy, intracerebral hemorrhage (ICH), and other diseases of the central nervous system (e.g., cognitive impairment, depression, sleep disorders, nightmare, and headache). Clinicians, especially neurologists, should be aware of the potential risk of neuropathy in patients who take statins.

The diagnosis of melanoma is still a clinical challenge, many studies reported that micropthalmia transcription factor (MITF) plays a role in diagnosing melanoma, but with considerable inconsistent results. The present work aimed to summarize the overall performance of MITF in diagnosing melanoma.A systematic literature search was performed in Pubmed and Embase for studies regarding the usefulness of MITF to diagnose melanoma. Data were retrieved and pooled sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were determined. The post-test probability was performed to evaluate clinical usefulness. A summary receiver operator characteristic curve and the area under the curve were used to summarize the overall diagnostic accuracy.Nine studies with 1,299 subjects (651 melanomas and 648 non-melanomas) were included for present meta-analysis. The pooled sensitivity and specificity of MITF for diagnosing melanoma were 0.84 (95% CI: 0.81-0.87) and 0.96 (95% CI: 0.95-0.98), respectively. The positive likelihood ratio was 17.73 (95% CI: 10.85-28.99), negative likelihood ratio was 0.18 (95% CI: 0.10-0.32) and diagnostic odds ratio was 221.56 (95% CI: 66.16-741.96). In a setting of 20% prevalence of melanoma, the probability of melanoma would be 92% if the MITF test was positive, and the probability of melanoma would be 1% if it was negative. The area under the summary receiver operator characteristic curve was 0.99.MITF may play a valuable role in the diagnosis of melanoma with a high specificity. Nevertheless, the results of MITF should be interpreted with the combination of other test results and clinical findings.

The diagnosis of lung cancer remains a clinical challenge. Many studies have assessed the diagnostic potential of anti-p53 antibody in lung cancer patients but with controversial results. This study aims to summarize the overall diagnostic performance of anti-p53 antibody in lung cancer.Based on a comprehensive search of the Pubmed and Embase, we identified outcome data from all articles estimating diagnostic accuracy of anti-p53 antibody for lung cancer. A summary estimation for sensitivity, specificity, and other diagnostic indexes were pooled using a bivariate model. The overall measure of accuracy was calculated using summary receiver operating characteristic curve and the area under curve (AUC) was calculated.According to our inclusion criteria, 16 studies with 4414 subjects (2249 lung cancers, 2165 controls) were included. The summary estimates were: sensitivity 0.20 (95% CI 0.15-0.27), specificity 0.97 (95% CI 0.95-0.98), positive likelihood ratio 6.64 (95% CI 4.34-10.17), negative likelihood ratio 0.83 (95% CI 0.77-0.89), diagnostic odds ratio 8.04 (95% CI 5.05-12.79), the AUC was 0.84. Subgroup analysis suggested that anti-p53 antibody had a better diagnostic performance for small cell lung cancer than non-small cell lung cancer.anti-p53 antibody can be an assistant marker in diagnosing lung cancer, but the low sensitivity limits its use as a screening tool for lung cancer. Further studies should be performed to confirm our findings.

Metastatic urothelial carcinoma portends a very poor long-term prognosis, with 5-year survival at approximately 5%. The overall survival of metastatic bladder cancer has not improved over the last 20 years. The first-line therapy is cisplatin-based chemotherapy with the response rate approximately 50%. Approximately 30-50% of the patients are unsuitable for cisplatin, and there is no standard of care for this patient population. There is no standard second-line treatment. Several signaling pathways are activated in bladder urothelial carcinoma, but no targeted therapy, either alone or in combination with conventional cytotoxic chemotherapy, has been shown to significantly improve the treatment outcomes. The future of metastatic urothelial carcinoma treatment lies in the ability to deliver personalized therapy. This area remains an active research field today.

Twenty-six species of human parasites were recorded in Zhejiang Province in 1987-1989 as a part of the national investigation on the distribution of human parasites, and the total prevalence was 80.2%. In order to find out possible changes on the composition of parasite species and decrease of prevalence after control intervention particularly mass chemotherapy in the past years and provide evidence for an improved control strategy, the second sampled survey was carried out from 1998 to 1999.Ten counties were identified randomly out of 28 counties where the last survey was conducted following the same sampling method. Same technics were used for case detection and data processing.The total infection rate in a sample of 15,698 was 22.84% was 22.84% in 30 investigation spots in 10 counties, and 17 species of parasites were revealed. The overall prevalence was reduced by 71.51% in comparison to that of 1989, and the number of parasite species was 17, 9 less than that of the last investigation.The prevalence of human parasites has greatly declined in this province due to the socioeconomic development and adoption of comprehensive control measures focusing on mass chemotherapy in the past decade.

G gamma(13) is a divergent member of the G gamma subunit family considered to be a component of the gustducin G-protein heterotrimer involved in bitter and sweet taste reception in taste bud cells. G gamma(13) contains a C-terminal asparagine-proline-tryptophan (NPW) tripeptide, a hallmark of RGS protein G gamma-like (GGL) domains which dimerize exclusively with G beta(5) subunits. In this study, we investigated the functional range of G gamma(13) assembly with G beta subunits using multiple assays of G beta association and G beta gamma effector modulation. G gamma(13) was observed to associate with all five G beta subunits (G beta(1-5)) upon co-translation in vitro, as well as function with all five G beta subunits in the modulation of Kir3.1/3.4 (GIRK1/4) potassium and N-type (alpha(1B)) calcium channels. Multiple G beta/G gamma(13) pairings were also functional in cellular assays of phospholipase C (PLC) beta 2 activation and inhibition of G alpha(q)-stimulated PLC beta 1 activity. However, upon cellular co-expression of G gamma(13) with different G beta subunits, only G beta(1)/G gamma(13), G beta(3)/G gamma(13), and G beta(4)/G gamma(13) pairings were found to form stable dimers detectable by co-immunoprecipitation under high-detergent cell lysis conditions. Collectively, these data indicate that G gamma(13) forms functional G beta gamma dimers with a range of G beta subunits. Coupled with our detection of G gamma(13) mRNA in mouse and human brain and retina, these results imply that this divergent G gamma subunit can act in signal transduction pathways other than that dedicated to taste reception in sensory lingual tissue.

The nerve growth factor, NGF, from Chinese cobra Naja naja atra venom was isolated by gel-filtration and ion-exchange chromatography. Cobra NGF was characterized by analytical HPLC techniques as well as SDS-PAGE, and was proven to be a glycoprotein with a mol. wt. of 23 (+/- 2) kD and a pI of 9.2. The amino acid analysis and N-terminal sequencing were performed using conventional methods. Bioassays with cultured chick embryos ganglia and rat pheochromocytoma PC-12 cells revealed a promotion of fiber outgrowth, which is typical of NGF activity. Absence of enzymatic, toxicological, and teratogenic activities were shown by quality inspection. Since 1994, many clinical cases about volunteers receiving NGF treatment have been reported in mainland China. Bioactivities of NGF deal with a wide range of disciplines and technologies. In this paper we will discuss neuronal and non-neuronal effects of NGF treatment. Does the NGF cross the blood-brain barrier by transcytosis into the brain tissue? How is NGF important in wound healing, especially in peripheral nerve injury and diabetic neuritis? NGF may also be useful for male volunteers suffering from sterility, because it is possible that the sexual cells of testis can be promoted to maturity.

Laparoscopic repair of inguinal hernias is gaining acceptance in the repertoire of the general surgeon. However, nerve entrapment sequelae have been reported and appear to be higher with the laparoscopic approach. Contributing factors include pelvic variations in nerve pathways and the use of staples. We examined the pelvic relations of the lateral femoral cutaneous nerve (LFCN) to the anterior superior iliac spine (ASIS) and the iliopubic tract (IPT) because of the high morbidity of entrapment of this nerve, despite its low incidence. The LFCN, ASIS, and IPT were identified and their relationships measured in 48 male and 24 female cadavers ranging in age from 61 to 96 yr. The LFCN was located 1.7 (+/- 1.2) cm medial to the ASIS along the IPT and 1.4 (+/- 0.7) cm posterior (deep) to the IPT at this point, with no significant sex differences. The intrapelvic pathway of the LFCN, including its branches, varied widely so that in 18% of these specimens the LFCN was in either the vertical plane of the ASIS (13%) or in the plane of the IPT (5%). In 11% this nerve was within 1 cm of the ASIS. These data indicate that exclusive use of the ASIS as a guide for staple placement may result in entrapment of this nerve or its branches.