AIM To observe the protective effects of mangiferin on the inflammatory injury and expression of the inflammatory factor in the cerebral tissue of spontaneously hypertensive rats and on MCP-1/CCR2 signal pathway.METHODS Forty spontaneously hypertensive rats were randomly divided into model,benazepril [10 mg/(kg · d)] and mangiferin high,middle and low dose [40,20,10 mg/(kg · d)] groups and other eight rats of same week age served as control group.After consecutive intragastric administration for eight weeks,morphology of the rats' cerebral tissue was observed;their levels of ICAM-1,IL-6 and TNF-α in cerebral tissue were determined by ELISA;their expressions of MCP-1 and CCR2 protein in brain tissue of rats were detected by immunohistochemistry and Western blot and the detection of mRNA expressions of MCP-1 and CCR2 in cerebral tissue of rats were carried out by RT-PCR.RESULTS Compared with the model group,the blood pressure of mangiferin in each dosage group decreased slightly,but there was no significant statistical difference.In the control group and the model group,there was no obvious morphological change in the cerebral tissue.The morphology of rats in the benazepril group,each dose of mangiferin group were all normal.The contents of IL-6,TNF-α,ICAM-1 and MCP1,CCR2 protein and mRNA expression were significantly decreased in the cerebral tissues of spontaneously hypertensive rats.CONCLUSION Mangiferin has obvious anti-inflammatory effects on inflammatory reaction in spontaneously hypertensive rats,its mechanism may be related to inhibiting the expression of MCP/CCR2 signaling pathway.

Objective: To retrospectively characterize and analyze the thyroid ultrasound images of thyroid cancer patients, to classify thyroid nodules according to thyroid imaging reporting and data system (TI-RADS), and to evaluate the diagnostic value of TI-RADS. Methods:Clinical data of 160 thyroid cancer patients with 235 nodules from September 2008 to August 2011 were retro-spectively analyzed. All patients underwent conventional color Doppler ultrasonography to evaluate the size, number, shape, boundary, and extent of lesions and blood distribution of the nodules. All nodules were analyzed according to TI-RADS classification and scored to evaluate the diagnostic value of TI-RADS. Results:Among 176 malignant nodules, 144 (81.8%) had lesions showing a mass of irreg-ular boundary with no envelope and halo, 152 (86.4%) were inhomogeneous hypoechoic or slightly hypoechoic, or 144 (81.8%) exhibit-ed microcalcification. TI-RADS scores of 4 or 5 and 2 or 3 were obtained in 160 (90.91%) and 16 (9.09%) of the malignant nodules, re-spectively. Conclusion:Thyroid ultrasound sonogram of ill-defined, irregular shape, hypoechoic or slightly hypoechoic mass, microcal-cification within the mass, and rich blood flow is an important index for the diagnosis of thyroid cancer. Thyroid nodules with a TI-RADS score 4 or 5 have higher possibility for cancer. Therefore, TI-RADS has a significant diagnostic value for thyroid cancer be-fore operation.

Objective To compare the value of assessment with DWI and contrast-enhanced MRI (CE-MRI) in activity of sacroiliitis of patients with ankylosing spondylitis(AS).Methods Ninety-six patients conforming to modified New York criteria were prospectively collectedas the AS group, and twenty-one healthy volunteers were enrolled into the control group. According to the Bath AS disease activity index (BASDAI), erythrocyte sedimentation rate and C-reaction protein, AS patients were divided into the active AS group (n=60) and the chronic AS group (n=36) . All subjects were performed with conventional MRI, DWI and CE-MRI of bilateral sacroiliac joints. The MRI manifestations were reviewed and the ADC values and signal intensity enhancement rate (ΔSI) were measured.ANOVA was performed for the comparison ofΔSI and ADC values among active AS group, chronic AS group and control group with BASDAI and lab test results as the gold standards. ROC was analyzed with ΔSI and ADC values for activity of AS and paired
samples t test was obtained to comparethe areas under the ROC ofΔSI and ADC values.Results Among 96 cases of AS patients, MRI of sacroiliac jointsshowed that 62 cases had subchondral bone edema (57 cases of active group, 5 cases of chronic group), that 11 cases had bone surface erosion(4 cases of active group, 7 cases of chronic group), that 15 cases had bone sclerosis(6 cases of active group, 9 cases of chronic group) and that 58 cases had fat deposition on the sacroiliac joints (27 cases of active group, 31 cases of chronic group). The ΔSI values of the active group, the chronic group and control group were respectively (2.51 ± 1.69)%,(1.19 ± 0.67)%and(0.75 ± 0.21)%, and the ADCvalues were(1.33 ± 0.33)× 10-3,(1.00 ± 0.43)× 10-3 and(0.38±0.13)×10-3mm2/s. There were significant differences forΔSI and ADC values among three groups (F=18.375, 16.366. P<0.01), and statistical significance ofΔSI and ADC values were found between every two groups of three(P< 0.05).The area under the ROC between ΔSI and ADC to determine activity of AS patients were respectively 0.814 and 0.730, which had nostatistical significance(t=1.632, P=0.103). The sensitivity and specificity to determine activity of AS patients byΔSI=1.44%were 81.67%and 80.00%.The sensitivity and specificity to determine activity of AS patients by ADC=1.15 × 10-3/mm2 were 76.67% and 71.43%.Conclusion DWI and CE-MRI performed equally in detecting activity of AS patients.

Metastasis is a multistep process involving modification of morphology to suit migration, reduction of tumor cell adhesion to the extracellular matrix, increase of cell mobility, tumor cell resistance to anoikis, and other steps. MicroRNAs are well-suited to regulate tumor metastasis due to their capacity to repress numerous target genes in a coordinated manner, thereby enabling their intervention at multiple steps of the invasion-metastasis cascade. In this study, we identified a microRNA exemplifying these attributes, miR-124, whose expression was reduced in aggressive MDA-MB-231 and SK-3rd breast cancer cells. Down-regulation of miR-124 expression in highly aggressive breast cancer cells contributed in part to DNA hypermethylation around the promoters of the three genes encoding miR-124. Ectopic expression of miR-124 in MDA-MB-231 cells suppressed metastasis-related traits including formation of spindle-like morphology, migratory capacity, adhesion to fibronectin, and anoikis. These findings indicate that miR-124 suppresses multiple steps of metastasis by diverse mechanisms in breast cancer cells and suggest a potential application of miR-124 in breast cancer treatment.
Anoikis ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Connective Tissue Growth Factor ; metabolism ; DNA Methylation ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; genetics ; metabolism ; Neoplasm Metastasis ; rho GTP-Binding Proteins ; metabolism ; rho-Associated Kinases ; metabolism

Objective To evaluate the effects of different sedation depths of propofol on postopera-tive delirium in patients undergoing cardiac valve replacement under cardiopulmonary bypass(CPB)and the relationship with regional cerebral oxygen saturation(rSO2). Methods Forty American Society of An-esthesiologists physical statusⅢorⅣpatients of both sexes, aged 26-64 yr, with body mass index of 17-25 kg∕m2, scheduled for elective aortic valve replacement with CPB, were divided into A and B groups (n=20 each)using a random number table. The infusion rate of propofol was adjusted to maintain the cor-responding anesthetic depth with 50≤BIS value<60 during CPB in group A and with 35≤BIS value<45 during CPB in group B. Bilateral rSO2was measured using the near infrared spectroscopy from admission to the operating room until the end of skin suturing. The minimum rSO2was recorded, and occurrence of low cerebral oxygen saturation(rSO2was less than 55% or the decrease in rSO2>20% of the baseline)was ob-served. Postoperative delirium was evaluated using Confusion Assessment Method for the Intensive Care Unit (ICU)from 12 h after admission to ICU until discharge from ICU. Results The incidence of postoperative delirium, low cerebral oxygen saturation and minimum rSO2were significantly lower in group B than in group A(P<005). Conclusion Maintaining 35≤ BIS value< 45 during CPB can reduce the develop-ment of postoperative delirium and is related to improving intraoperative rSO2in patients undergoing cardiac valve replacement.

Objective: To evaluate the effect of anesthesia management based on regional cerebral oxygen saturation (rSO₂)-bispectral index (BIS)-goal-directed hemodynamic multi-modal monitoring on acute kidney injury (AKI) after cardiac valve replacement. Methods: A total of 238 patients of both sexes, aged 18-75 yr, weighing 45-95 kg, of American Society of Anesthesiologists physical status Ⅲ or Ⅳ (New York Heart Association class Ⅱ or Ⅲ ), undergoing elective cardiac valve replacement, were assigned into routine experience group (group C, n=122) and multi-mode monitoring group (group M, n=116) using a random number table method.After admission to the operating room, the invasive blood pressure of radial artery, central venous pressure, electrocardiogram, SpO₂ and end-tidal pressure of carbon dioxide were recorded in group C, and rSO₂, BIS, stroke volume variation, cardiac index and stroke volume index were monitored based on the monitoring in group C. The patients were tracheally intubated when BIS value was about 50.BIS value was maintained between 45 and 55, rSO₂ was maintained not less than 20% of the baseline value or the absolute value not less than 55%, and fluctuation in mean arterial pressure did not exceed 20% of the baseline value, and stroke volume index was maintained >25 ml/m² and cardiac index>2.5 L·min^-1 ·m^-2, maintaining not lower than the baseline value before induction in special conditions.The intraoperative volume of fluid infused, infusion of allogeneic blood, consumption of propofol, time of cardiopulmonary bypass, aortic cross-clamping time, anesthesia time, operation time, occurrence of AKI within 48 h after operation, renal replacement therapy, extubation time, duration of intensive care unit stay, postoperative length of hospital stay, development of other serious postoperative complications and fatality rate at day 30 after operation were recorded. Results: Compared with group C, the incidence of AKI was significantly decreased, the volume of plasma infused and consumption of propofol were reduced, the extubation time, duration of intensive care unit stay and postoperative length of hospital stay were shortened (P<0.05), and no significant change was found in the rate of renal replacement therapy, constituent ratio of AKI degree, incidence of other serious postoperative complications or mortality rate at day 30 after operation in group M (P>0.05). Conclusion Anesthesia management based on rSO₂-BIS-goal-directed hemodynamic multi-modal monitoring can decrease the occurrence of AKI after cardiac valve replacement.

OBJECTIVE: The compatibility of Eucommia ulmoides (Eu) and Psoralea corylifolia (Pc) on the pharmacokinetic (PK) properties in the rat was explored in this study. METHODS: Eu extract, Pc extract and the combined extracts (crude drug ratio was 2:1) was administered by gavage, respectively. Two PK experiments were conducted. In first one, the blood samples were collected via the occuli chorioideae vein to get the PK properties of the components. In second one, the blood samples were simultaneously collected via the internal jugular vein or portal vein at different time points and the concentrations of target ingredients were detected by LC/MS/MS to clear the location where the interaction of Eu and Pc took place in vivo. RESULTS: Eight of 11 ingredients in Eu and Pc extract were determined in rat plasma. The exposure levels of geniposidic acid (GPA), aucubin (AU), geniposide (GP), pinoresinol diglucoside (PDG), psoralen glycosides (PLG) and isopsoralen glycosides (IPLG) were decreased 1/5-2/3 after administration of combined extracts. Comparing to the combined administration, the exposure of GPA and AU in plasma of single Eu administration collected via the portal vein were decreased 1/3-2/3, and the values of AUC_0-24h and AUC_0-∞ of GP collected from the portal vein or internal jugular vein were double increased. The other components' parameters were not significantly changed. CONCLUSION In summary, the Pc and Eu combined administration could affect the exposure of the main components of Eu extract in rats due to the changed intestinal absorption. The research on the compatibility of Pc and Eu was helpful to guide the clinical administration of Eu and Pc simultaneously.

OBJECTIVE: Hypertension is a low-grade inflammation state of the disease and was easily complicated by kidneys' inflammatory response. Mangiferin (MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-inflammatory activity. However, the effects of MGF on renal inflammatory injury in spontaneously hypertensive rats (SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal inflammatory injury in SHRs. METHODS: MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological, immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR (RT-PCR) analysis. RESULTS: The results showed that the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and recombinant chemokine C-C-Motif receptor 2 (CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-α, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen (BUN) and serum uric acid (SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels. CONCLUSION Our study proved that the kidneys of SHRs had significant inflammatory injury, and MGF had the protective effects on renal inflammatory injury in SHRs; The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.

Alzheimer's disease （AD） is one of the most common diseases in the elderly population. Its etiology involves multiple pathogenic factors and pathological links such as abnormal deposition of β amyloid protein （Aβ）， hyperphosphorylation of Tau protein， abnormalities of the cholinergic system， oxidative stress， and inflammatory response. However， its specific pathogenesis has not been clarified， and no specific therapeutic drugs have been found. In recent years， more and more studies have paid attention to the potential of chemical components of traditional Chinese medicine （TCM） in the treatment of AD. However， the diversity and complexity of the chemical components of TCM may have a positive impact on multiple pathological links of AD. Researchers have isolated many active components from TCMs， and the effects of treating AD have been confirmed by modern pharmacological studies. Through literature analysis， this article found that the main chemical components of TCM with anti-AD effects were saponins （31%）， flavonoids （24%）， polysaccharides （20%）， lactones （8%）， alkaloids （7%）， phenols （3%）， and other compounds （7%）. Among them， ginsenoside， notoginsenoside， epimedium flavones， puerarin， baicalein， schisandra polysaccharide， angelica polysaccharide， ganoderma lucidum polysaccharide， pachyman， huperzine A， berberine， andrographolide， curcumin， emodin， and gastrodin have been extensively studied in terms of their anti-AD effects， and their mechanisms of pharmacological action have been involved in many aspects of AD pathogenesis. This article reviews the anti-AD activities and possible mechanisms of chemical components of TCM， so as to provide a reference for the development of new drugs for the prevention and treatment of AD.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems