Objective: To understand the pathogenesis of bisphosphonate-related osteonecrosis of the jaws (BRONJ) and to investigate its differential diagnosis, clinical manifestations, treatment and prevention. Methods: By analyzing the clinical data of 4 patients with BRONJ in the retrospective study with reviewing related literatures in the world to make a summary of it Results: Cases of 4 patients mainly presented recurring pain, discharging of pus and disposure and necrosis of the bone. 3 patients received surgical and antibiotics treatments, one of them had local infection which was under control by oral antibiotic. The other 2 patients had no infection and recurrence. Conclusion BRONJ is caused by jaw necrosis due to bisphosphonate inhibition of osteoclast function. For the reason that none of the treatments is unified and satisfied, we should focus on the risk factors in prevention. Appropriate surgery treatment could be well controlled the process of the BRONJ which should be popularization in our study.

OBJECTIVETo study the relationship between the fibrinogen content in middle ear effusion (MEE) and the protracted inflammation of secretory otitis media (SOM) and to explore the possible mechanism of batroxobin in treatment of SOM.

METHODSThe fibrinogen content of middle ear effusion from 156 patients with SOM was investigated with concretion technique at different stages. After two times punctuation of tympanum, the recurrence patients were randomly divided into two groups: batroxobin and dexamethasone group, and 0.5 ml (2 BU/ml) batroxobin or dexamethasone (2 mg/ml) was injected into middle ear cavity. The therapeutic effects were investigated.

RESULTSThe concentration of fibrinogen in the recurrence group of SOM patients was higher than that in the cured group, and even higher in the second recurrence group than in the first recurrence group (P < 0.01). There was significantly different (P < 0.001) in the therapeutic efficacy between the batroxobin group (91.6%) and the dexamethasone group (62. 5%); the difference of the fibrinogen content in MEE and air conduction of pure tone audiometry at frequencies (0.5, 1.0, 2.0 kHz) between the two groups after treatment were also significant (P < 0.01).

CONCLUSIONSFibrinogen may play a significant role in the occurrence and development of secretory otitis media. Batroxobin had better therapeutic effect on SOM than dexamethasone. The mechanism of batroxobin in the treatment of SOM may be that the batroxobin can relief the depressant effect of fibrinogen on surface active agents of the Eustachian tube and prevent the fibrinogen from turning into insoluble fibrin polymer by means of fibrinolysis.

Adolescent ; Adult ; Aged ; Batroxobin ; therapeutic use ; Dexamethasone ; therapeutic use ; Ear, Middle ; secretion ; Female ; Fibrinogen ; analysis ; metabolism ; Humans ; Inflammation ; Male ; Middle Aged ; Otitis Media with Effusion ; drug therapy ; metabolism ; Young Adult

The aim of this study is to prepare porous γ-cyclodextrin metal-organic framework (CD-MOF) with good biocompatibility to improve the in vitro release properties of water-insoluble drugs. Different sizes of CD-MOF were obtained by controlling the self-assembly of γ-cyclodextrin and potassium ion and the rate of crystal growth. The poorly water-soluble diflunisal (DIF) was selected as the model drug and loaded into the interior of porous CD-MOF by the impregnation method. The DIF loaded CD-MOF (DIF-MOF) was characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), nitrogen adsorption and desorption, Fourier infrared spectrometer and thermogravimetric analysis. In addition, in vitro cytotoxicity and solubilizing capability of CD-MOF were investigated. It revealed that the obtained CD-MOF was cubic-like with a narrow size distribution and high porosity. Negligible cytotoxicity was found after incubation with RAW264.7 cells. Compared with the pure CD-MOF carrier, the morphology and crystal form of DIF-MOF was not damaged during the drug loading process. Moreover, the solubility and release rate of water-insoluble DIF from the DIF-MOF were significantly increased.

Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Guanine ; adverse effects ; analogs & derivatives ; therapeutic use ; Hepatitis B ; complications ; drug therapy ; Humans ; Liver Cirrhosis ; complications ; drug therapy ; Male ; Middle Aged ; Peripheral Nervous System Diseases ; chemically induced ; complications

The aim of this study was to determine the dynamic expression profile of hepatitis B surface antigen (HBsAg) according to hepatic parenchyma cells' volume at different stages of liver fibrosis during the immune clearance phase. Eighty-nine patients with HBeAg-positive chronic hepatitis B (CHB) in the immune clearance stage were recruited for study. Each patient's serum HBsAg levels were detected by electrochemiluminescence. The serum HBsAg levels were apportioned according to hepatic parenchyma cells' volume at liver fibrosis stages 1, 2, 3, and 4 and compared by ANOVA. The unapportioned serum HBsAg levels (IU/mL) at liver fibrosis stages 1 (227.2+/-237.7), 2 (211.0+/-131.4), 3(300.1+/-144.6), and 4 (278.7+/-148.8) were not significantly different (all comparisons, P range: 0.061 to 0.759). However, when the serum HBsAg levels were apportioned by the same hepatic parenchyma cells' volume at liver fibrosis stages 1 (343.9+/-359.8), 2 (336.4+/-209.5), 3 (508.7+/-245.1), and 4 (525.2+/-274.8), the levels were significantly different (all comparisons, F = 3.045 and P = 0.033; stage 1 vs. 3, P = 0.041; stage 1 vs. 4, P = 0.046; stage 2 vs. 3, P = 0.028; stage 2 vs. 4, P = 0.034). During the immune clearance phase of chronic hepatitis B, increased HBsAg expression is associated with increased hepatic parenchyma cells' volume and progressive liver fibrosis stage.
Adolescent ; Adult ; Cell Size ; Child ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B, Chronic ; metabolism ; pathology ; Humans ; Liver ; cytology ; metabolism ; Liver Cirrhosis ; metabolism ; pathology ; Male ; Middle Aged ; Young Adult

ObjectiveTo investigate whether hsa_circ_0002316 （circOMA1） is involved in drug resistance in prolactinoma and its mechanism. MethodsRT-qPCR was used to dectect the expression of circOMA1 in clinical prolactinoma specimens including 5 dopamine receptor agonists （DAs）-sensitive prolactinomas and 12 DAs-resistant prolactinomas. MMQ cell lines with stable expression of exogenous circOMA1 were constructed by lentivirus vector infection for in vitro experiment， and were divided into MMQ NC group and MMQ OMA1 group. Xenograft tumor models in nude mice were established for in vivo experiment， and were divided into MMQ NC+cabergoline （CAB） group， MMQ NC+bromocriptine （BRC） group， MMQ OMA1+CAB group and MMQ OMA1+BRC group. CCK8， Western blot and ELISA were performed to detect the effects of circOMA1 on cell proliferation and secretion of prolactin （PRL） in drug resistance mechanism. Western blot， ELISA and immunohistochemistry were used to examine the effect of circOMA1 on dopamine receptor expression. The mechanism of circOMA1 regulating dopamine receptor was explored by TargetScan， CircInteractome and microRNA-145-5p （miR-145-5p） minic remediation experiment. ResultsRT-qPCR showed that circOMA1 expression was increased in DAs-resistant prolactinomas （P < 0.01）. Compared with MMQ NC group， MMQ OMA1 group had lower DAs sensitivity and increased cell proliferation and prolactin secretion （P < 0.05） in vivo and in vitro. Western blot and immunohistochemical analysis showed that in MMQ OMA1 group， the expression of dopamine receptor type 2 （DRD2） was down-regulated， and the expression of dopamine receptor type 5 （DRD5）， the cyclic 3 'and 5' -adenosine monophosphine （cAMP） was up-regulated （P < 0.05）. In MMQ OMA1 group， miR-145-5p expression was down-regulated， kelch repeat sequence and BTB domain-containing protein 7 （KBTBD7） mRNA and protein expression was up-regulated （P < 0.05）. After transfected with miR-145-5p minic， MMQ OMA1 group exhibited down-regulated KBTBD7 expression and up-regulated DRD2 expression （P < 0.05）， which indicated that overexpression of miR-145-5p reversed the promoting effect of circOMA1 on KBTBD7. ConclusionCircOMA1 down-regulated DRD2 expression through miR-145-5p/KBTBD7 pathway to reduce the sensitivity of prolactinoma to DAs， and regulated the expression of dopamine receptors to activate the cAMP pathway and promote the synthesis and release of prolactin， thus promoting the drug resistance in prolactinoma.

【Objective】To investigate the role of ER stress and PUMA in 5-FU-induced liver cells injury and apoptosis.【Methods】We established 5-FU-induced liver injury models by intraperitoneally injecting the isodose 5-FU to 10 PUMA knockout mice(PUMA-KO)and 20 PUMA Wild type mice(PUMA-WT). Meanwhile,10 WT mice were intraperitoneally injected with 4-Phenylbutyric acid,the ER stress inhibitor. In the control group,10 KO mice and 20 WT mice were given the same amount of normal saline.After the modeling,serum and liver tissues of the mice were collected to assess the degree of liver pathological injury,measure the expression levels of ALT and AST in serum,and detect the expression levels of PUMA and GRP78 in liver tissues. The changes of these indicators in different treatment groups were observed and compared.【Results】Compared with the WT control group,serum ALT and AST levels were significantly increased in the 5-FU group,H&E staining showed punctate focal necrosis,accompanied by hemorrhage and inflammation. TUNEL staining showed apoptotic cells were markedly added(Z = 3.78,P < 0.001),and expressions of PUMA and GRP78 were obviously augmented,suggesting that both PUMA and ER stress were involved in 5-FU-induced liver cells injury and apoptosis. Then,in the 4-PBA group,we found that the expression levels of GRP78 and PUMA were down-regulated,and apoptosis of liver cells was reduced under the same dose of 5-FU(χ~2= 32.99,Z = 3.78,P <0.001),further confirming that both PUMA and ER stress were involved in this process. Subsequently,it was found that,when induced by the same dose of 5-FU,cleaved caspase-3 staining showed that the liver apoptosis signal of the PUMA knockout mice was lower than the WT mice(χ~2= 33.99,Z = 3.78,P < 0.001),but the difference in the expression of GRP78 between the two groups was not statistically significant. In summary,the expression of PUMA was reduced and the apoptosis of liver cells was attenuated after the inhibition of ER stress;PUMA knockdown could not influence the activation of ER stress but alleviated apoptosis of liver cells.【Conclusions】PUMA mediates ER stress-up-regulated liver cells apoptosis in 5-FU-induced Chemotherapeutic liver injury.

OBJECTIVETo investigate the association of Pro12Ala variant in peroxisome proliferator-activated receptor-gamma2 gene with type 2 diabetes mellitus and its clinical characteristics.

METHODSThe genotypes of Pro12Ala variant in peroxisome proliferator-activated receptor-gamma2 gene were determined by polymerase chain reaction-restriction fragment length polymorphisms assay in 401 unrelated subjects of the Han population in the southern part of China (including 180 subjects with normal glucose tolerance and 221 type 2 diabetic patients). The clinical data were also analyzed.

RESULTSThe allele frequencies in the case and control groups were 96.15%,96.11% for P and 3.85%, 3.89% for A; the genotype frequencies were 92.77%, 92.22% for PP, 6.78%, 7.78% for PA and 0.45%, 0 for AA. The Pro12Ala variant of peroxisome proliferator-activated receptor-gamma2 was not significantly associated with type 2 diabetes. The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma2 in diabetes patients was associated with increased waist circumference and waist to hip ratio. The Pro12Ala polymorphism in Chinese population was similar to that in Japanese population and was different from that in European and American population.

CONCLUSIONThe above data showed that the Pro12Ala variant of peroxisome proliferator-activated receptor-gamma2 was not significantly associated with type 2 diabetes, but it could be associated with abdominal obesity in type 2 diabetes. The significant difference of Pro12Ala of peroxisome proliferator-activated receptor-gamma2 among various races was observed.

Adult ; Alanine ; genetics ; Alleles ; Amino Acid Substitution ; Blood Glucose ; metabolism ; Body Constitution ; Body Mass Index ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Diabetes Mellitus, Type 2 ; blood ; genetics ; pathology ; Female ; Gene Frequency ; Genotype ; Humans ; Insulin ; blood ; Male ; Middle Aged ; Proline ; genetics ; Receptors, Cytoplasmic and Nuclear ; genetics ; Transcription Factors ; genetics ; Triglycerides ; blood

OBJECTIVETo evaluate the effect of different cleaners on the color stability of two silicone rubbers used for maxillofacial prosthesis, and to provide recommendations for clinical use.

METHODSThirty skin-color columniform specimens (12 mm diameter, 10 mm height) of two silicone rubber (A:A-2000; Z:ZY-1) were prepared, randomly divided into 6 groups according to the table of random number, and cleaned with the following solutions: isopropyl alcohol (I), three kinds of denture cleaners (P: Polident, S: Steradent, C: Cleansoft) and distilled water (D), simulating the total immersion time of 1 year (1, 15, 10, 3 and 10 min each time respectively). Control group was kept in dark place without treatment. The L(*), a(*), b(*) value were tested before and after immersion. Then color difference value was calculated.

RESULTSColor differences were different among groups. Color difference in group I (A: 2.15, Z: 2.00) were significantly greater than that in any other group. There were no significant differences between groups using denture cleaner P (A: 0.36, Z: 0.36), C (A: 0.42, Z: 0.37) and S (A: 0.33, Z: 0.38), and group D (A: 0.22, Z: 0.23).

CONCLUSIONSIsopropyl alcohol causes the most severe fading, and denture cleaners and distilled water cause obscure fading.

2-Propanol ; chemistry ; Borates ; chemistry ; Color ; Denture Cleansers ; chemistry ; Materials Testing ; Maxillofacial Prosthesis ; Phosphates ; chemistry ; Prosthesis Coloring ; Silicone Elastomers ; Sodium Chloride ; chemistry ; Sulfates ; chemistry

The hydroxycamptothecin (HCPT) PEGylated liposomes (HCPT-LP) were modified with RGD cyclopeptide formed the tumor-targeting liposomes (HCPT-RGD-LP). HCPT-LP and HCPT-RGD-LP were injected intravenously with single dose of 5 mg x kg(-1) to rats. The drug concentration in plasma was determined and the pharmacokinetic behaviour was compared. The HCPT distribution in heart, liver, spleen, lung, kidney and plasma of mice was investigated following intravenous administration of HCPT-LP and HCPT injection. The nude mice implanted human hepatoma HepG2 cells were studied by in vivo imaging. The fluorescent probe was DiR and the nude mice were injected with DiR PEGylated liposomes (DiR-LP) and DiR-LP modified with RGD cyclopeptide (DiR-RGD-LP). The results showed that there was no significant difference (P > 0.05) of main pharmacokinetic parameters t1/2beta, CL, V(c), AUC(0-48 h), AUC(0-inifinity), MRT(0-48 h), MRT(0-infinity) between HCPT-RGD-LP and HCPT-LP. HCPT-LP had a remarkably better long-circulating effect than HCPT injection in mice and the concentration of HCPT was highest in liver. The DiR accumulation in tumors of DiR-RGD-LP was higher than that of DiR-LP by the visualized fluorescence of in vivo imaging. It indicated that such PEGylated liposomes modified with RGD cyclopeptide could improve the tumor targeting efficacy.
Animals ; Area Under Curve ; Camptothecin ; administration & dosage ; analogs & derivatives ; chemistry ; pharmacokinetics ; Diagnostic Imaging ; Drug Delivery Systems ; Female ; Fluorescent Dyes ; Hep G2 Cells ; Humans ; Liposomes ; administration & dosage ; chemistry ; pharmacokinetics ; Liver Neoplasms ; diagnosis ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Oligopeptides ; administration & dosage ; chemistry ; pharmacokinetics ; Polyethylene Glycols ; administration & dosage ; chemistry ; pharmacokinetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectroscopy, Near-Infrared ; Tissue Distribution