OBJECTIVETo evaluate the usefulness of quantitative electroencephalogram (QEEG), flash visual evoked potential (F-VEP) and auditory brainstem responses (ABR) as indicators of general neurological status.

METHODSComparison was conducted on healthy controls (n = 30) and patients with brain concussion (n = 60) within 24 h after traumatic brain injury. Follow-up study of patient group was completed with the same standard paradigm 3 months later. All participants were recorded in multi-modality related potential testing in both early and late concussion at the same clinical setting. Glasgow coma scale, CT scanning, and physical examinations of neuro-psychological function, optic and auditory nervous system were performed before electroencephalogram (EEG) and evoked potential (EEG-EP) testing. Any participants showed abnormal changes of clinical examinations were excluded from the study. Average power of frequency spectrum and power ratios were selected for QEEG testing, and latency and amplitude of F-VEP and ABR were recorded.

RESULTSBetween patients and normal controls, the results indicated: (1) Highly significance (P < 0.01) in average power of α1 and power ratios of θ/α1, θ/α2, α1/α2 of EEG recording; (2) N70-P100 amplitude of F-VEP in significant difference at early brain concussion; and (3) apparent prolongation of I-III inter-peak latency of ABR appeared in some individuals at early stage after concussion. The follow-up study showed that some patients with concussion were also afflicted with characteristic changes of EEG components for both increments of α1 average power and θ/α2 power ratio after 3 months recording.

CONCLUSIONEEG testing has been shown to be more effective and sensitive than evoked potential tests alone on detecting functional state of patients with mild traumatic brain injury (MTBI). Increments of α1 average power and θ/α2 power ratio are the sensitive EEG parameters to determining early concussion and evaluating outcome of post-concussion symptoms (PCS). Follow-up study associated with persistent PCS may be consistent with the postulate of substantial biological, rather than psychological origin. The study suggests that combination of EEG and EP parameters can contribute to the evaluation of brain function as a whole for clinical and forensic applications.

PURPOSE: This study assessed the environmental lead exposure in patients with chronic kidney disease (CKD) and the relationship between lead exposure and renal function indices. METHODS: Seventy-one patients with CKD and 40 control subjects without known renal disease were included. Blood lead was measured by atomic absorption spectrophotometry and tibial lead was measured via 109Cd-based K-shell X-ray fluorescence. Blood urea nitrogen (BUN), serum creatinine, urine creatinine and urine N-acetyl-beta glucosaminidase (NAG) were also measured. Blood lead was corrected with hematocrit (female: 35%, male: 42%) to adjust for differences in anemic status of patients compared with control subjects. RESULTS: The mean level of hematocrit-adjusted blood lead was significantly higher in patients with CKD (4.18+/-1.74 microg/dL) compared with that in control subjects (3.00+/-0.92 microg/dL); the mean tibial lead level tended to be higher in patients with CKD (3.38+/-9.93 microg/g) than that in control subjects (1.28+/-7.92 microg/g), but no statistical significance was observed. In a multivariate regression analysis after adjusting for gender, age, and drinking and smoking status, adjusted blood lead was a significant predictor of increases in BUN and serum creatinine, but not of the level of urine NAG or creatinine. In contrast, no significant association between tibial lead and renal indices was observed in the multivariate regression analysis. CONCLUSION: These results suggest that environmental lead exposure may compromise renal function.
Blood Urea Nitrogen ; Creatinine ; Drinking ; Fluorescence ; Hematocrit ; Hexosaminidases ; Humans ; Renal Insufficiency, Chronic ; Smoke ; Smoking ; Spectrophotometry, Atomic

Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.
Dendritic Cells/immunology ; Female ; Genetic Vectors ; Humans ; *Immunotherapy ; Papillomavirus Infections/*complications/therapy ; Papillomavirus Vaccines/therapeutic use ; *Translational Medical Research ; Uterine Cervical Neoplasms/*therapy ; Vaccines, DNA/therapeutic use ; Vaccines, Subunit/therapeutic use

Proteins of the complement system are known to interact with many charged substances. We recently characterized binding of C1q and factor H to immobilized and liposomal anionic phospholipids. Factor H inhibited C1q binding to anionic phospholipids, suggesting a role for factor H in regulating activation of the complement classical pathway by anionic phospholipids. To extend this finding, we examined interactions of C1q and factor H with lipid A, a well-characterized activator of the classical pathway. We report that C1q and factor H both bind to immobilized lipid A, lipid A liposomes and intact Escherichia coli TG1. Factor H competes with C1q for binding to these targets. Furthermore, increasing the factor H: C1q molar ratio in serum diminished C4b fixation, indicating that factor H diminishes classical pathway activation. The recombinant forms of the Cterminal, globular heads of C1q A, B and C chains bound to lipid A and E. coli in a manner qualitatively similar to native C1q, confirming that C1q interacts with these targets via its globular head region. These observations reinforce our proposal that factor H has an additional complement regulatory role of down-regulating classical pathway activation in response to certain targets. This is distinct from its role as an alternative pathway down-regulator. We suggest that under physiological conditions, factor H may serve as a downregulator of bacterially-driven inflammatory responses, thereby fine-tuning and balancing the inflammatory response in infections with Gram-negative bacteria.
Binding, Competitive ; immunology ; Complement Activation ; immunology ; Complement C1q ; chemistry ; immunology ; metabolism ; Complement C4b ; analysis ; Complement Factor H ; chemistry ; immunology ; metabolism ; Complement Pathway, Classical ; immunology ; Escherichia coli ; immunology ; metabolism ; Humans ; Iodine Radioisotopes ; Isotope Labeling ; Lipid A ; immunology ; metabolism ; Liposomes ; immunology ; metabolism ; Protein Binding ; immunology ; Recombinant Proteins ; chemistry ; immunology ; metabolism ; Substrate Specificity

OBJECTIVETo study the effect of Tiantai No. 1 [symbol in text] on gene expression profile in hippocampus of Alzheimer's disease (AD) rat, molecular genetic target points of the effect of this drug were defined, its molecular genetic pharmacodynamic mechanism of anti-AD was further explored at molecular gene level, and a scientific basis was provided for its clinical availability and promotion.

METHODSThirty male Sprague-Dawley rats were divided into three groups with 10 rats per group: sham-operation group, model group and Tiantai No. 1 group. Sterile surgical procedure was applied, the model group with bilateral hippocampal injection of Aβ1-40 was established, and normal saline was used instead of Aβ1-40 in the sham-operation group. One week after the models was made, rats were administered by gastric lavage once every day for three consecutive weeks. The rats of the sham-operation group and the model group were daily fed with purified water by lavage; the rats of the Tiantai No.1 group treated group were administered with Tiantai No.1 by lavage. Total RNAs of hippocampus tissues were extracted with Trizol, the changes of hippocampus gene expression profiles in the above three groups were analyzed by using Affymetrix rat whole genome expression profile microarray.

RESULTSMicroarray analysis showed that, compared with the sham-operation group, the hippocampus of the model group had 50 up-regulated genes with significant difference (fold change >2), and 21 down-regulated genes with significant difference (fold change <0.5); compared with the hippocampus of the model group, the hippocampus of the Tiantai No. 1 group was found to have 5 up-regulated genes with significant difference (fold change >2) and 20 down-regulated genes with significant difference (fold change <0.5). The functions of differentially expressed genes of the groups were involved in nervous system's development, neuronic differentiation and function-regulation, cellular growth and differentiation and apoptosis, synaptic occurrence and plasticity, inflammation and immune response, ion channels/transporters, cellular signal transduction, cellular material/energy metabolism and so on.

CONCLUSIONTiantai No. 1 can regulate hippocampal function, and further regulate the brain function of animals in multiple gene target points by a number of ways.

Alzheimer Disease ; genetics ; pathology ; Animals ; Body Weight ; drug effects ; Computational Biology ; methods ; Drugs, Chinese Herbal ; pharmacology ; Electrophoresis, Agar Gel ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Hippocampus ; drug effects ; metabolism ; pathology ; Male ; Nucleic Acid Denaturation ; Organ Size ; drug effects ; RNA ; isolation & purification ; metabolism ; Rats, Sprague-Dawley

OBJECTIVEChanges of the internal and external cellular environments can induce calcium homeostasis disorder and unfolded protein aggregation in the endoplasmic reticulum (ER). This ER function disorder is called endoplasmic reticulum stress (ERS). Severe long-term ERS can trigger the ER apoptosis signaling pathway, resulting in cell apoptosis and organism injury. Recent researches revealed that ERS-induced cell death was involved in the neurocyte retrogradation in the progress of neuron degenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease and so on. Therefore, the protection effect of the traditional Chinese drug-Tiantai No. 1 (1) on the ERS injury of AD was investigated at the molecular gene level in this study with a view to explore the gene pharmacodynamic actions and mechanisms of this drug.

METHODSPrimarily cultured marrow mesenchymal stem cells (MSCs) of rats were treated by tunicamycin (TM) in order to induce ERS. RT-PCR, fluorescence immunocytochemistry and Western blot techniques were used to determine the mRNA and protein expression levels of the protective stress protein-ER molecular chaperones GRP78 and GRP94 (which would assist cells to resist cellular stress injury), and to determine the mRNA and protein expression levels of apoptosis promoting molecule Caspase-12 on the membrane of the ER, respectively.

RESULTSProtein expression levels of GRP78 and GRP94 were significantly increased in the TM-induced MSCs, and the mRNA level of Caspase-12 was also remarkably increased in the TM-induced MSCs (P<0.05). All these proved that the ERS model was successfully established by TM in MSC. Meanwhile, the mRNA and protein levels of GRP78 and GRP94 were all significantly increased compared with the model group (P<0.05 or P<0.01) after MSCs were treated with Tiantai No.1 while the mRNA and protein expression levels of Caspase-12 were significantly decreased compared with the model group (P<0.05 or P<0.01). This effect showed a dose dependent manner.

CONCLUSIONTiantai No.1 might attenuate the cell apoptosis induced by ERS injury, and thus protect the neurons against AD.

Animals ; Anti-Bacterial Agents ; antagonists & inhibitors ; pharmacology ; Cells, Cultured ; Drug Antagonism ; Drugs, Chinese Herbal ; pharmacology ; Endoplasmic Reticulum ; drug effects ; metabolism ; Gene Expression Regulation ; drug effects ; Heat-Shock Proteins ; genetics ; metabolism ; Male ; Membrane Glycoproteins ; genetics ; metabolism ; Mesenchymal Stromal Cells ; drug effects ; metabolism ; RNA ; analysis ; drug effects ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Stress, Physiological ; drug effects ; genetics ; Tunicamycin ; antagonists & inhibitors ; pharmacology

BACKGROUNDBoth real-time three-dimensional echocardiography (RT3DE) and myocardial contrast echocardiography (MCE) are novel imaging techniques. The purpose of this study was to confirm the feasibility and accuracy of RT3DE combined with MCE for quantitative evaluation of myocardial perfusion defects.

METHODSThirteen dogs underwent ligation of the left anterior descending artery (LAD, n = 6) or distal branch of the left circumflex artery (LCX, n = 7) under general anaesthesia. Three to four ml of a perfluoropropane (C3F8) microbubble contrast agent was injected intravenously to assess the resulting myocardial perfusion defects with a commercially available Philips SONOS-7500 ultrasound system. After removal of the dog hearts, Evans blue dye was injected via the left and right coronary arteries to stain the myocardium at risk. In vitro anatomic measurements of myocardial mass after removal of the animals' hearts were used as controls.

RESULTSLeft ventricular (LV) mass determined by RT3DE ranged 36.7 - 68.9 g [mean, (54.6 +/- 9.6) g] before coronary artery ligation, and correlated highly (r = 0.99) with in vitro measurement of LV mass [range, 38.9 - 71.1 g; mean, (55.6 +/- 9.3) g]. There was no significant difference between RT3DE and in vitro measurements of LV mass [range, 36.7 - 68.9 g; mean, (51.3 +/- 12.5) g. Or range, 38.9 - 71.1 g; mean, (53.7 +/- 12.3) g, respectively] and under-perfused mass [range, 0 - 21.4 g; mean, (12.0 +/- 6.9) g. Or range, 0 - 19.8 g; mean, (10.8 +/- 6.3) g, respectively] after the LAD ligation (P > 0.05). Likewise, no significant difference was present between RT3DE and in vitro measurements of LV mass [range, 50.1 - 65.4 g; mean, (57.5 +/- 5.9) g. Or range, 51.5 - 65.8 g; mean, (57.3 +/- 6.4) g, respectively] and under-perfused mass [range, 0 - 25.6 g; mean, (13.3 +/- 9.6) g. Or range, 0 - 22.7 g; mean, (12.8 +/- 8.1) g, respectively] after the LCX ligation (P > 0.05). For all the animals with coronary ligation, LV mass measured by RT3DE ranged 35.9 - 68.6 g [mean, (54.8 +/- 10.0) g] and there was no significant difference between RT3DE and in vitro measurements of LV mass and under-perfused mass (P > 0.05, r = 0.99). Further, the under-perfused mass derived from RT3DE [range, 0 - 25.6 g; mean, (12.7 +/- 8.2) g] correlated strongly with the in vitro measurements [range, 0 - 22.7 g; mean, (11.9 +/- 7.2) g] (r = 0.96).

CONCLUSIONRT3DE with MCE is a rapid and accurate method for estimating LV myocardial mass and quantifying perfusion defects.

Animals ; Coronary Disease ; diagnostic imaging ; Dogs ; Echocardiography ; Echocardiography, Three-Dimensional ; Feasibility Studies ; Fluorocarbons

Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive than surgery with comparable efficacy. The present guidelines (the “2019 Seoul Consensus on Esophageal Achalasia Guidelines”) were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10 pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could use these guidelines to make an informed decision on the management of achalasia.

Objectives. Polymorphisms in metabolic genes which alter rates of bioactivation and detoxification have been shown to modulate susceptibility to colorectal cancer. This study sought to evaluate the colorectal cancer risk from environmental factors and to do polymorphism studies on genes that code for Phase I and II xenobiotic metabolic enzymes among Filipino colorectal cancer patients and matched controls. Methods. A total of 224 colorectal cancer cases and 276 controls from the Filipino population were genotyped for selected polymorphisms in GSTM1, GSTP1, GSTT1, NAT1 and NAT2. Medical and diet histories, occupational exposure and demographic data were also collected for all subject participants.Results. Univariate logistic regression of non-genetic factors identified exposure to UV (sunlight) (OR 1.99, 95% CI: 1.16-3.39) and wood dust (OR 2.66, 95% CI: 1.21-5.83) and moldy food exposure (OR 1.61, 95% CI:1.11-2.35) as risk factors; while the NAT2*6B allele (recessive model OR 1.51, 95% CI :1.06-2.16; dominant model OR 1.87, 95% CI: 1.05-3.33) and homozygous genotype (OR 2.19, 95% CI: 1.19-4.03) were found to be significant among the genetic factors. After multivariate logistic regression of both environmental and genetic factors, only UV radiation exposure (OR 2.08, 95% CI: 1.21-3.58) and wood dust exposure (OR 2.08, 95% CI: 0.95-5.30) remained to be significantly associated with increasing colorectal cancer risk in the study population.Conclusion. This study demonstrated that UV sunlight and wood dust exposure play a greater role in influencing colorectal cancer susceptibility than genotype status from genetic polymorphisms of the GST and the NAT` genes.
Colorectal Neoplasms ; Polymorphism, Genetic

BACKGROUND: The comparative outcomes of subcutaneous implantable cardioverter-defibrillator (S-ICD) and transvenous ICD (T-ICD) have not been well studied. The aim of this study was to evaluate the safety and efficacy of currently available S-ICD and T-ICD. METHODS: The study included 86 patients who received an S-ICD and 1:1 matched to those who received single-chamber T-ICD by gender, age, diagnosis, left ventricular ejection fraction (LVEF), and implant year. The clinical outcomes and implant complications were compared between the two groups. RESULTS: The mean age of the 172 patients was 45 years, and 129 (75%) were male. The most common cardiac condition was hypertrophic cardiomyopathy (HCM, 37.8%). The mean LVEF was 50%. At a mean follow-up of 23 months, the appropriate and inappropriate ICD therapy rate were 1.2% vs. 4.7% (χ = 1.854, P = 0.368) and 9.3% vs. 3.5% (χ = 2.428, P = 0.211) in S-ICD and T-ICD groups respectively. There were no significant differences in device-related major and minor complications between the two groups (7.0% vs. 3.5%, χ = 1.055, P = 0.496). The S-ICD group had higher T-wave oversensing than T-ICD group (9.3% vs. 0%, χ = 8.390, P = 0.007). Sixty-five patients had HCM (32 in S-ICD and 33 in T-ICD). The incidence of major complications was not significantly different between the two groups. CONCLUSIONS The efficacy of an S-ICD is comparable to that of T-ICD, especially in a dominantly HCM patient population. The S-ICD is associated with fewer major complications demanding reoperation.
Adult ; Cardiomyopathy, Hypertrophic ; physiopathology ; therapy ; Death, Sudden, Cardiac ; prevention & control ; Defibrillators, Implantable ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Tachycardia, Ventricular ; physiopathology ; therapy