Bexarotene is a synthetic analogue of retinoic acid and exerts protective effects on the nervous system. However, low bioavailability and poor solubility of the crystal type I form severely limits the application of bexarotene in the clinic. A co-amorphous sample of bexarotene-PVP-K30 was prepared and the structure was characterized by X-ray diffraction and infrared spectroscopy. To determine the pharmacokinetics and tissue distribution of bexarotene, an LC-MS method was established to profile and quantify bexarotene in plasma and tissues of SD rats. In vitro dissolution indicated that the co-amorphous form improved the dissolution of bexarotene in pure water 4.17-fold. After rats were orally administered bexarotene or bexarotene-PVP-K30 co-amorphous (equivalent to 30 mg·kg^-1 bexarotene) the AUC of bexarotene was 7 034.89 and 10 174.03 μg·L^-1·h respectively, the peak time was advanced from 7.33 h to 0.9 h with the amorphous form, and C_max was enhanced from 627.76 to 3 011.88 μg·L^-1. The co-amorphous form yielded higher concentrations of bexarotene in various tissues, especially brain, liver and kidney. Animal welfare and experimental procedures complied with the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. The results indicate that bexarotene-PVP-K30 co-amorphous improves the pharmacokinetic characteristics of bexarotene and provides preclinical data in support of bexarotene-PVP-K30 for the treatment of brain diseases.

Objective To discuss the effects of polybrominated diphenyl ethers （PBDEs） exposure in e-waste dismantling region on the human body and provide data support for the identification of environmental health damage to residents in the e-waste dismantling region. Methods Adults in an e-waste dismantling region （exposed group, 54 participants） and a control region （control group, 58 participants） were selected, questionnaires were carried out and blood and urine samples were collected. Blood PBDEs, blood lipids, blood routine, blood lead, urine cadmium, urine chromium and urine nickel were detected. T-test was utilized to compare the differences of PBDEs between the two groups. Multivariate analysis were utilized to compare the differences between the two groups in blood routine indexes. Linear regression was used to analyze the relationship between PBDEs and blood routine. Results Exposure levels of PBDEs were significantly higher in the exposed group （240.00 ng/g, adjusted mass fraction of blood lipids, thereafter） than in the control group （93.00 ng/g, P<0.05）. There was no statistical significance in the differences in most blood routine indexes of the two groups （ P>0.05）, and their reference values were all within normal ranges. Mean platelet volume, plateletcrit, basophils percentage, absolute value of basophils, and mean corpuscular hemoglobin concentration were higher in the exposed group than in the control group （P<0.05）. Platelet distribution widths were lower in the exposed group than in the control group and below the normal reference range （P<0.05）. Conclusion PBDEs exposure in e-waste dismantling region tend to change platelet morphology, the number of basophils, and mean corpuscular hemoglobin concentration, and may pose potential health hazards to local residents.
Adult ; China ; Electronic Waste/analysis* ; Environmental Monitoring ; Halogenated Diphenyl Ethers/toxicity* ; Human Body ; Humans

Objective To investigate the effect of safranal on neurologic functions and histopathologic changes after spinal cord injury (SCI)and the related molecular mechanisms.Methods We randomly assigned 36 rats into six groups:control group,injury group and four treatment groups (namely,A,B,C,and D).The Basso Beattie Bresnahan locomotor rating scale (BBB)and HE staining were applied to evaluate the neuroprotective effect and determine the most effective dosage.Another 60 rats were randomly and evenly assigned to three groups:control group,injury group and treatment group.Nissl staining,TUNEL staining and electron microscopy were used to analyze histopathological changes;RT-PCR,immunohistopathological staining,ELISA,and Western blot were used to detect the expressions of apoptosis-related proteins (Bax and Bcl-2 ),inflammation-related factors (IL-1β, IL-10,TNF-αand P38MAPK),and edema-related factor (APQ-4).Results The optimal dosage for safranal was 100 mg/kg.Neurocyte structure was found more distinct in treatment group than in injury group.In addition,we detected a smaller number of apoptotic neurocyte (26.37±1.54 vs.35.94±1.62,P=0.000),decreased Bax (P=0.000)and APQ-4[(359.55±16.12)% vs.(124.53±20.35)%,P=0.000]expressions,increased Bcl-2 (P=0.036)expression,and obviously lowered P38MAPK [(300.30±33.26)% vs.(132.54±10.21)%,P=0.000]expression. Conclusion Safranal exerts its neuroprotective function through anti-apoptosis,anti-inflammation and anti-edema in the rat model of spinal cord injury.

Objective To discuss the clinical application of percutaneous transhepatic removal of gall-stone technique in treating common bile duct (CBD) stones.Methods Between January 2013 and January 2015,a total of 25 patients with CBD stones underwent lithotomy procedure via percutaneous transhepatic route.First,under ultrasound or fluoroscopy guidance percutaneous transhepatic cholangiography (PTC) was performed with subsequent placement of an 8 F rsheath;then,a balloon of 8-12 mm diameter was employed to dilate the papilla;mechanical lithotripsy was adopted when the stone size exceeded 12 mm;finally,through guide-wire exchange technique the stone-retrieval balloon was used to push the stones into the intestinal tract through the sphincter of duodenal papilla.Results The reasons to receive percutaneous transhepatic removal of gall-stone technique in the 25 patients included previous gastrointestinal surgery (n=18),endoscopic treatment failure (n=3),unwilling to receive endoscopic treatment (n=3),and other reasons (n=1).Successful removal of stones was accomplished in all 25 patients.After the treatment,complications occurred in 3 patients (12％),including fever (n=2) and liver abscess formation (n=1).The patients were followed up for 0.5-3 years;two patients died of tumor recurrence and metastasis,and one patient developed recurrence of common bile duct stones.No reflux cholangitis occurred.Conclusion For the treatment of CBD stones,percutaneous transhepatic removal of gall-stone technique carries higher technical success rate with lower incidence of complications,therefore,this technique can be used for the patients who are not suitable for endoscopic treatment or in whom endoscopic treatment failed.

Aim To investigate the influence of down-regulating adenosine A1 receptor and adenosine A2 A receptor gene expression on proliferation and activation of acetaldehyde-induced hepatic stellate cell-T6 cells through siRNA. Methods Alcoholic liver fibrosis in vitro model was constructed by inducing HSC-T6 cells with acetaldehyde. siRNA targeting A1R and A2AR were designed and synthesized according to its mRNA. The siRNA was transfected into rat HSC-T6 cells by li-posome LipofectamineTM 2000. HSC cell proliferation was measured by MTT. The mRNA levels of A1R, A2AR, α-SMA, Collagen I in the supernatant of the cell culture were measured by Quantitative Real-Time PCR. The protein levels of A1R, A2AR, α-SMA, Collagen I were measured by Western blot. Results A1 R and A2 AR siRNA effectively inhibited the cell proliferation, and they also significantly decreased the levels of A1R, A2AR,α-SMA, Collagen I, suggesting that A1 R and A2 AR might be potential target genes in the alcoholic liver fibrosis. Conclusions Silencing A1 R or A2 AR by RNAi can significantly inhibit the HSC proliferation, A1R and A2AR may be potential therapeutic target genes for alcoholic liver fibrosis.

Adult ; Female ; Humans ; Hypercalcemia ; diagnosis ; surgery ; Hyperparathyroidism ; diagnosis ; surgery ; Male ; Middle Aged ; Parathyroid Neoplasms ; diagnosis ; surgery

OBJECTIVETo evaluate the effects of two gastric cancer screening schemes for early detection of gastric cancer in a high-risk population.

METHODSA cluster random sampling method was used to select local residents aged 40-69 years from Linqu County, Shandong Province. "Serum pepsinogen initial screening combined with further endoscopic examination (PG scheme)" and "direct endoscopic examination (endoscopy scheme)" were conducted. The associations between screening schemes and detection rates of gastric cancer, and early gastric cancer/high-grade intraepithelial neoplasia were evaluated by unconditional logistic regression analysis.

RESULTSOverall, 3654 and 2290 participants completed PG and endoscopy schemes, respectively. A total of 11 (0.30%) cases of gastric cancer and 10 (0.27%) cases of high-grade intraepithelial neoplasia were detected by PG scheme, of which 7 (0.19%) cases were early gastric cancer. While, 19 (0.83%) cases of gastric cancer and 10 (0.44%) cases of high-grade intraepithelial neoplasia were detected by endoscopy scheme, with 12 (0.52%) cases of early gastric cancer. Compared with the PG scheme, the endoscopy scheme had a significantly higher detection rates of gastric cancer (OR = 2.83, 95%CI 1.34-5.98), and early gastric cancer/high-grade intraepithelial neoplasia (OR = 2.12, 95%CI 1.12-4.02).

CONCLUSIONSThe endoscopy scheme is more effective in the detection of gastric cancer in a high-risk population, particularly for early gastric cancer/high-grade intraepithelial neoplasia than the PG scheme.

Adult ; Aged ; Carcinoma ; blood ; diagnosis ; Carcinoma in Situ ; blood ; diagnosis ; Early Detection of Cancer ; methods ; Female ; Gastroscopy ; Humans ; Male ; Mass Screening ; methods ; Middle Aged ; Pepsinogen A ; blood ; Stomach Neoplasms ; blood ; diagnosis

BACKGROUNDCyanotic congenital heart defects with decreased pulmonary blood flow due to lung ischemia, hypoxia, and others lead to infant morbidity and mortality more than acyanotic heart disease does. Despite the great effort of medical research, their genetic link and underlying microRNAs molecular mechanisms remain obscure. In this study, we aimed to investigate microRNAs regulation during cyanotic defects in lung of immature piglets.

METHODSCyanotic piglet model was induced by main pulmonary artery-left atrium shunt with distal pulmonary artery banding. Four weeks later, hemodynamic parameters confirmed the development of cyanotic defects and pulmonary lobe RNA was extracted from all animals. We studied the repertoire of porcine lung microRNAs by Solexa deep sequencing technology and quantified highly expressed microRNAs by microarray hybridization. Furthermore, we quantitated selected microRNAs from cyanotic and control piglets by quantitative RT-PCR.

RESULTSAfter surgical procedure 4 weeks later, the cyanotic model produced lower arterial oxygen tension, arterial oxygen saturation, and higher arterial carbon dioxide tension, hematocrit and hemoglobin concentration than controls (all P < 0.05). In 1273 miRNAs expressed in the immature piglets lungs, 2 most abundant microRNAs (miR-370 and miR-320) demonstrated significant difference between cyanotic and control group (all P < 0.05).

CONCLUSIONOur results extended lung microRNA profile in immature piglets and suggested that miR-370 and miR-320 are significantly up-regulated in cyanotic lung tissues.

Animals ; Chronic Disease ; Cyanosis ; genetics ; physiopathology ; Gene Expression Profiling ; Heart Atria ; surgery ; MicroRNAs ; analysis ; physiology ; Pulmonary Artery ; surgery ; Pulmonary Circulation ; Real-Time Polymerase Chain Reaction ; Swine ; Swine, Miniature

OBJECTIVETo study the clinical and laboratory features and diagnosis of the patient with anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis in children.

METHODThe data of clinical feature, laboratory findings, and radiological manifestation were reviewed and analyzed.

RESULTOf the 7 patients, 4 were female and 3 were male. The age of onset was from 6.6 to 15.5 years (average 9.5 years). The onset of 4 cases started with convulsion. Six cases had seizures which was difficult to control by antiepileptic drugs. All patients had psychiatric symptoms and speech disorder. Six cases had different levels of decreased consciousness and dyskinesias. 6 cases had autonomic nerve instability, and 7 cases developed sleep disorders. The results of MRI examination were normal in all patients. The EEG of most patients showed focal or diffuse slow waves. Six cases had oligoclonal bands. All cases were confirmed to have the disease by detection of anti-NMDA receptor antibodies. No tumor was detected in any of the patients. All patients received immunotherapy.

CONCLUSIONAnti-NMDAR encephalitis is a severe but treatable disorder that frequently affects children and adolescents. Pediatric patients had clinical manifestations similar to those of adult patients. But children have a lower incidence of tumors and hypoventilation also occurs less frequently in children. Most of children had a good prognosis.

Adolescent ; Anti-N-Methyl-D-Aspartate Receptor Encephalitis ; complications ; diagnosis ; therapy ; Autoantibodies ; blood ; cerebrospinal fluid ; Autonomic Nervous System ; physiopathology ; Brain ; diagnostic imaging ; pathology ; Child ; Electroencephalography ; Female ; Humans ; Immunotherapy ; methods ; Magnetic Resonance Imaging ; Male ; Movement Disorders ; etiology ; Radiography ; Receptors, N-Methyl-D-Aspartate ; immunology ; Retrospective Studies ; Seizures ; etiology

BACKGROUNDCyanotic patients have potential growth retardation and malnutrition due to hypoxemia and other reasons. Ghrelin is a novel endogenous growth hormone secretagogue that has effects on growth and cardiovascular activities. The aim of this study was to evaluate the plasma level and myocardial expression of ghrelin and insulin-like growth factor-1 (IGF-1) using an immature piglet model of chronic cyanotic congenital heart defects with decreased pulmonary blood flow.

METHODSTwelve weanling Chinese piglets underwent procedures of main pulmonary artery-left atrium shunt with pulmonary artery banding or sham operation as control. Four weeks later, hemodynamic parameters were measured. Enzyme-linked immunosorbent assay for plasma ghrelin and IGF-1 level measurement were performed. Ventricular ghrelin and IGF-1 mRNA expressions were measured by quantitative real-time polymerase chain reaction.

RESULTSFour weeks after surgical procedure, the cyanotic model produced lower arterial oxygen tension ((68.73 ± 15.09) mmHg), arterial oxygen saturation ((82.35 ± 8.63)%), and higher arterial carbon dioxide tension ((51.83 ± 6.12) mmHg), hematocrit ((42.67 ± 3.83)%) and hemoglobin concentration ((138.17 ± 16.73) g/L) than the control piglets ((194.08 ± 98.79) mmHg, (96.43 ± 7.91)%, (36.9 ± 4.73) mmHg, (31.17 ± 3.71)%, (109.83 ± 13.75) g/L) (all P < 0.05). Plasma ghrelin level was significantly higher in the cyanotic model group in comparison to the control (P = 0.004), and the plasma IGF-1 level was significantly lower than control (P = 0.030). Compared with control animals, the expression of ghrelin mRNAs in the ventricular myocardium was significantly decreased in the cyanotic model group (P = 0.000), and the expression of IGF-1 mRNAs was elevated (P = 0.001).

CONCLUSIONSChronic cyanotic congenital heart defects model was successfully established. Plasma ghrelin level and myocardial IGF-1 mRNA expression were significantly up-regulated, while plasma IGF-1 level and myocardial ghrelin mRNA expression were down-regulated in the chronic cyanotic immature piglets. The ghrelin system may be an important part of the network regulating cardiac performance.

Animals ; Cyanosis ; blood ; metabolism ; physiopathology ; Female ; Ghrelin ; blood ; metabolism ; Heart Defects, Congenital ; blood ; metabolism ; physiopathology ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Male ; Pulmonary Circulation ; physiology ; Swine