Objective: To integrate the toxic component of cantharidin (CTD) into a novel nanostructured lipid carrier (NLC) and optimize the cantharidin nanostructured lipid carrier (CTD-NLC) formulation process to reduce the toxicity of CTD and enhance its targeting. Methods: CTD-NLC was prepared by emulsified ultrasonic dispersion method. The encapsulation efficiency was determined by dialysis method. The average particle size, particle size distribution (polydispersity index, PDI), Zeta potential, encapsulation efficiency, and drug loading were taken as indicators. Univariate investigation and central composite design-response surface methodology (CCD-RSM) were used to optimize the prescription process of CTD-NLC. Multivariate quadratic fitting was used to evaluate the model equation between indicators and factors. The fitted equation was analyzed by the variance analysis and the optimal prescription was predicted by the resonse surface. Results: The optimized CTD-NLC prescriptions were as follow: mass of total lipid was 453.66 mg, solid to liquid lipid ratio of 1:2, total stable dose of 16.9 mg/mL, ratio of Pluronic F68 to egg yolk lecithin (Lipoid E PC S) of 3.88:1, with ultrasound for 30 min (working 2 s, stopping 2 s). The prepared CTD-NLC was clear clarification in appearance with light blue opalescence, the average particle size was (85.99 ± 0.49) nm, PDI was 0.280 ± 0.002, Zeta potential was (-8.21 ± 0.24) mV, encapsulation efficiency was (98.57 ± 0.05)%, and drug loading was (0.65 ± 0.01)%. Conclusion: The fitting model established by CCD-RSM is accurate and reliable. The optimized CTD-NLC distribution is concentrated, with high encapsulation efficiency and good physical stability. It lays a foundation for the subsequent in vitro and in vivo studies of CTD-NLC.

OBJECTIVE: To evaluate the spontaneous brain activity alterations in liver transplantation (LT) recipients using resting-state functional MRI. MATERIALS AND METHODS: Twenty cirrhotic patients as transplant candidates and 25 healthy controls (HCs) were included in this study. All patients repeated the MRI study one month after LT. Amplitude of low-frequency fluctuation (ALFF) values were compared between cirrhotic patients (both pre- and post-LT) and HCs as well as between the pre- and post-LT groups. The relationship between ALFF changes and venous blood ammonia levels and neuropsychological tests were investigated using Pearson's correlation analysis. RESULTS: In the cirrhotic patients, decreased ALFF in the vision-related regions (left lingual gyrus and calcarine), sensorimotor-related regions (left postcentral gyrus and middle cingulate cortex), and the default-mode network (bilateral precuneus and left inferior parietal lobule) were restored, and the increased ALFF in the temporal and frontal lobe improved in the early period after LT. The ALFF decreases persisted in the right supplementary motor area, inferior parietal lobule, and calcarine. The ALFF changes in the right precuneus were negatively correlated with changes in number connection test-A scores (r = 0.507, p < 0.05). CONCLUSION: LT improved spontaneous brain activity and the results for associated cognition tests. However, decreased ALFF in some areas persisted, and new-onset abnormal ALFF were possible, indicating that complete cognitive function recovery may need more time.
Ammonia ; Brain* ; Cognition ; Fibrosis ; Frontal Lobe ; Hepatic Encephalopathy ; Humans ; Liver Transplantation* ; Liver* ; Magnetic Resonance Imaging ; Motor Cortex ; Neuropsychological Tests ; Occipital Lobe ; Parietal Lobe ; Rabeprazole ; Somatosensory Cortex

OBJECTIVESTo discuss the methods and outcome of shorting proximal femoral and total hip arthroplasty for Crowe IV dysplastic hip of adults.

METHODSFrom July 2000 to February 2006, 13 cases of osteoarthritis secondary to severe development dysplastic hip were treated by total hip replacement and the shorting proximal femoral.

RESULTSThe duration of follow-up ranged from 4 months to 55 months. The average score increased from 36.9 to 84.1 points after the surgery according to Harris. All the patients could walk independently. Their paces were improved obviously and the function of their hips was satisfactory.

CONCLUSIONSThe treatment by total hip arthroplasty and the shorting of posterior femoral is effective and efficient for osteoarthritis secondary to Crowe IV development dysplastic hip in adults. The long-term followup is necessary for further study.

Adult ; Aged ; Arthroplasty, Replacement, Hip ; methods ; Female ; Femur ; surgery ; Follow-Up Studies ; Hip Dislocation ; etiology ; surgery ; Humans ; Male ; Middle Aged ; Osteotomy ; methods ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo study the feasibility of using tetracysteine (TC) reporter in gene therapy.

METHODSEffects of TC reporter and conventional reporter genes encoding green fluorescence protein (GFP) and luciferase (Luc) on expression and function of the therapeutic gene MGMT(P140K) were compared. Cytotoxicity and drug resistance were studied by Western blot. TC reporter used in therapy was analyzed by flow cytometry (FCM).

RESULTSThe TC reporter had no toxicity to cells and neither affected the expression or activity of therapeutic gene as compared to GFP and Luc. TC could be used in blood sample detection.

CONCLUSIONTC is a new kind of reporter gene for lentiviral vector in future gene therapy.

Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Cysteine ; analogs & derivatives ; genetics ; metabolism ; Gene Expression Regulation ; Genes, Reporter ; Genetic Therapy ; Humans ; Lentivirus ; genetics ; Lymphocytes ; metabolism

AIMTo determine the biochemical effect of di-(2-ethylhexyl) phthalate (DEHP) on testes, liver, kidneys and pancreas on day 10 in the process of degeneration of the seminiferous epithelium.

METHODSDiets containing 2% DEHP were given to male Crlj:CD1(ICR) mice for 10 days. The dose of DEHP was 0.90 +/- 0.52 mg/mouse/day. Their testes, livers, kidneys and pancreata were examined for detection of mono-(2-ethylhexyl) phthalate (MEHP), nitrogen oxides (NOx) produced by peroxidation of nitric oxide (NO) with free radicals, and lipid peroxidation induced by the chain reaction of free radicals.

RESULTSHistological observation and serum analysis showed the presence of severe spermatogenic disturbance, Leydig cell dysfunction, liver dysfunction and dehydration. Unexpectedly, the concentration of MEHP in the testes was extremely low compared with that in the liver. However, the concentration of the NOx in the testes was as high as the hepatic concentration. Furthermore, free radical-induced lipid peroxidation was histochemically detected in the testes but not in the liver.

CONCLUSIONThe results indicate that DEHP-induced aspermatogenesis is caused by the high sensitivity of the testicular tissues to MEHP rather than the specific accumulation or uptake of circulating MEHP into the testes.

Animals ; Body Weight ; drug effects ; Copper ; metabolism ; Diethylhexyl Phthalate ; analogs & derivatives ; metabolism ; pharmacology ; Iron ; metabolism ; Kidney ; drug effects ; metabolism ; Lipid Peroxidation ; drug effects ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Nitrogen Oxides ; metabolism ; Pancreas ; drug effects ; metabolism ; Spermatogenesis ; drug effects ; Testis ; drug effects ; metabolism ; Testosterone ; blood ; Zinc ; metabolism

Objective To evaluate the role of preoperative serological indexes in predicting long-term survival and tumor recurrence of hepatocellular carcinoma (HCC) patients after liver transplantation, aiming to explore its significance in expanding the Milan criteria. Methods Clinical data of 669 recipients undergoing liver transplantation for HCC were retrospectively analyzed. The optimal cut-off value was calculated by the receiver operating characteristic (ROC) curve. The risk factors affecting the overall survival and recurrence-free survival rates of HCC patients after liver transplantation were identified by univariate and multivariate regression analyses. The correlation between preoperative serum liver enzymes and pathological characteristics in HCC patients was analyzed. The predictive values of alpha-fetoprotein (AFP) combined with γ -glutamyl transferase (GGT) and different liver transplant criteria for the survival and recurrence of HCC patients after liver transplantation were compared. Results Exceeded Milan criteria, total tumor diameter (TTD) > 8 cm, AFP > 200 ng/mL and GGT > 84 U/L were the independent risk factors for the overall survival and recurrence-free survival rates of HCC patients after liver transplantation (all P < 0.05). Correlation analysis showed that preoperative serum GGT level was correlated with TTD, number of tumor, venous invasion, microsatellite lesions, capsular invasion, tumor, node, metastasis (TNM) stage, Child-Pugh score and exceeded Milan criteria (all P < 0.05). Milan-AFP-GGT-TTD (M-AGT) criteria were proposed by combining Milan criteria, TTD with serum liver enzyme indexes (AFP and GGT). The 5-year overall survival and recurrence-free survival rates of HCC recipients who met the M-AGT criteria (111 cases of exceeded Milan criteria) were significantly higher than those who met Hangzhou criteria (both P < 0.05), whereas had no significant difference from their counterparts who met the University of California at San Francisco (UCSF) criteria (both P > 0.05). Conclusions Preoperative serological indexes of AFP and GGT could effectively predict the long-term survival and tumor recurrence of HCC patients after liver transplantation. Establishing the M-AGT criteria based on serological indexes contributes to expanding the Milan criteria, which is convenient and feasible.

OBJECTIVETo evaluate the value of transbronchial needle aspiration (TBNA) combined with transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of mediastinal and pulmonary hilar lesions as well as in the lymph node staging (N staging) of lung cancer.

METHODS129 patients with mediastinal and pulmonary hilar lesions underwent either TBNA or EUS-FNA with cytological needle aspiration. The samples obtained from TBNA or EUS-FNA were examined by both cytologiy and histopathology.

RESULTSOf the 129 patients, 59 underwent TBNA and 70 EUS-FNA. The diagnostic rate were 84.7% (50/59) by TBNA and 94.3% (66/70) by EUS-FNA, resepectively. The diagnosis of 116 (89.9%) patients were confirmed by either TBNA or EUS-FNA. The pathological and cytological diagnostic rates were 92.2% (107/116) and 88.0% (102/116), resepectively. The diagnostic rate was elevated by 8.4% (9/107) through pathological examination. The histological classification rates by cytological and pathological examination were 73.8% (76/116) and 89.3% (92/103), respectively. The diagnostic rate of histological classification was elevated by 35.5% (27/76) through pathological examination.

CONCLUSIONThe combination of TBNA and EUS-FNA can improve the diagnostic rate for wider mediastinal and pulmlonary hilar lesions. Pathological examination of the samples obtained from the TBNA and EUS-FNA can elevate not only the rate of diagnosis but also the rate of histological classification.

Adenocarcinoma ; diagnostic imaging ; pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle ; methods ; Biopsy, Needle ; Carcinoma, Squamous Cell ; diagnostic imaging ; pathology ; Endosonography ; methods ; Female ; Humans ; Lung Neoplasms ; diagnostic imaging ; pathology ; Lymph Nodes ; diagnostic imaging ; pathology ; Lymphatic Metastasis ; Male ; Mediastinal Neoplasms ; diagnostic imaging ; pathology ; secondary ; Mediastinum ; Middle Aged ; Neoplasm Staging ; Small Cell Lung Carcinoma ; diagnostic imaging ; pathology ; Young Adult

OBJECTIVETo investigate the effect of combined occupational exposure of chromium and iron on erythrocyte metabolism, and the possible mechanism.

METHODSA total of 115 chromate production workers were selected in a chemical factory of Jinan as exposure group, Dec, 2008, and 60 healthy residents from a community which was far away from the factory were enrolled as control group. Environmental concentrations of chromium and iron were collected by filter membrane sampling and determined. The peripheral blood of subjects were collected for determination of chromium, iron, copper in whole blood and folate, vitamin B₁₂ in serum, mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) and correlation analysis was conducted.

RESULTSThe median (quartile interval) concentration of air-chromium and air-iron in workplace were 9.0 (10.5) and 11.2 (10.1) µg/m³, respectively, which were significantly higher than that of the control (0.1 (0.1) and 7.2 (2.5) µg/m³) (all P values < 0.01). Blood-chromium and blood-iron of the exposed group were 15.5 (14.1) µg/L and (895.1 ± 90.2) mg/L, which were significantly higher than the counterpart of the control (3.6(2.0) µg/L, (563.7 ± 49.3) mg/L) (all P values < 0.01). Serum folate ((6.9 ± 2.5) µg/L), serum vitamin B₁₂ ((396.4 ± 177.0) µg/L) and blood copper ((777.6 ± 103.5) µg/L) of the exposed group were all significantly lower comparing to the control group ((558.0 ± 330.8), (8.1 ± 3.8), (812.1 ± 94.6) µg/L) (all P values < 0.05). The relationships between blood chromium and serum folate, serum vitamin B₁₂ were statistical significant (r = -0.319 and -0.293, P < 0.01). Both serum vitamin B₁₂ and blood copper correlated with mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) (r = -0.223, -0.242, -0.261, -0.292, all P values < 0.01).

CONCLUSIONCombined chromium and iron exposure existed in the workplace. Adverse effect of Chromium on human erythrocyte may via folate and vitamin B₁₂ metabolism, while iron may via copper metabolism.

Air Pollutants, Occupational ; Chromates ; adverse effects ; Chromium ; adverse effects ; Copper ; blood ; Erythrocytes ; metabolism ; Folic Acid ; blood ; Humans ; Iron ; adverse effects ; Occupational Exposure ; analysis ; Vitamin B 12 ; blood

This study was aimed to investigate the radioprotective effects of recombinant human interleukin-12 (rhIL-12) on monkey hematopoietic system, and to provide experimental evidence for future clinical prophylaxis and treatment for patients who suffered from acute radiation syndrome. In in vitro study, the effect of rhIL-12 in different concentrations (0, 1, 5, 25, 125 and 625 ng/ml) on colony forming capacity of human or monkey bone marrow-derived mononuclear cells was examined in methylcellulose H4434 medium. In in vivo study, the acute radiation syndrome model was established in 11 Rhesus monkeys which received lethal total body irradiation by 6 Gy (60)Co γ in single time irradiation. The irradiated monkeys were randomly divided into 3 subgroups: control group (n = 4) which received subcutaneous PBS injection, rhIL-12 single-dose group (n = 3) which received subcutaneous single injection of rhIL-12 (4 µg/kg) at 2 h after irradiation, and multiple-dose group (n = 4) which received subcutaneous injection of rhIL-12 (1 µg/kg per injection) at 2 h, day 3, 6 and 9 after irradiation respectively. Peripheral blood cells were counted before and after irradiation every other day. The survival status of animals were observed daily. In vitro test results showed that different concentrations of rhIL-12 obviously promoted human and healthy monkeys' bone marrow mononuclear cells to form various hematopoietic progenitor cell colonies, especial CFU-E and CFU-GM. All animals in control group died within 22 d after lethal total body irradiation, average survival time was (20.3 ± 1.2) d. Only one monkey in multiple-dose group died due to anemia on day 17. All monkeys in single-dose group survived. Compared with control group, rhIL-12-administrated monkeys' white blood cell count, hemoglobin level, platelet and reticulocyte counts showed faster recovery from high dose radiation. It is concluded that the rhIL-12 treatment can promote the bone marrow hematopoietic stem/progenitor cell colony formation in vitro and protect lethally-irradiated monkeys. There is an obvious therapeutic effect of rhIL-12 on monkeys suffered from bone marrow failure caused by severe acute radiation exposure.
Animals ; Bone Marrow Cells ; cytology ; drug effects ; radiation effects ; Cells, Cultured ; Hematopoietic Stem Cells ; drug effects ; radiation effects ; Humans ; Interleukin-12 ; pharmacology ; Macaca mulatta ; Radiation-Protective Agents ; pharmacology ; Recombinant Fusion Proteins ; pharmacology

AIM:To explore the effects of genipin (GEN) on high glucose (HG) -induced oxidative stress injury and apoptosis in H9c2 cardiomyocytes.METHODS:H9c2 cells were cultured in vitro and HG-induced injury model was established.H9c2 cells were divided into 4 groups:normal control (NC) group (glucose at 5.6 mmol/L) , HG group (glucose at 50 mmol/L) , NG+GEN group and HG+GEN group.The concentration of genipin was used at 10μmol/L.The viability of the H9c2 cells was measured by CCK-8 assay.The intracellular malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were determined by enzyme labeling and WST-1 methods, respectively.The activity of lactate dehydrogenase (LDH) in the cell culture supernatant was detected by microplate method.Fluorescent probe DCF was used to detect intracellular levels of reactive oxygen species (ROS).Nucleosome fragments was measured to evaluate cell apoptosis by ELISA.The intracellular mitochondrial membrane potential was detected by JC-1 method.The protein levels of Mn-SOD, cytochrome C (Cyt C) , Bax and cleaved caspase-3 were determined by Western blot.RESULTS:Compared with HG group, the cell viability in HG+GEN group was increased significantly (P<0.05) , the levels of MDA and LDH were decreased (P<0.05) , SOD activity was increased (P<0.05) , the levels of ROS and nucleosome fragments in HG+GEN group were decreased (P<0.05) , and the mitochondrial membranes potential was notably increased (P<0.05).Compared with NG group, the activation of Mn-SOD was decreased, but the protein levels of Cyt C, Bax and cleaved caspase-3 were increased in HG group (P<0.05).Compared with HG group, the activation of Mn-SOD was increased, and the protein levels of Cyt C, Bax and cleaved caspase-3 were decreased in HG+GEN group (P<0.05).CONCLUSION:Genipin protects HG-induced H9c2 cardiomyocytes against oxidative stress injury and apoptosis.