Animals ; Gene Silencing ; physiology ; Gene Targeting ; Genetic Therapy ; methods ; Genomics ; Humans ; RNA Interference ; RNA, Small Interfering ; genetics ; therapeutic use ; RNA-Induced Silencing Complex

The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide—arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2 ± 7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17 ± 1.88) %, an encapsulation rate (5.85 ± 0.72) %, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.

OBJECTIVETo investigate the possible role of STAT3 and p38 in the carcinogenesis of sporadic colorectal tubular adenoma.

METHODSThe expression of STAT3 and p38 at protein level was studied in 107 sporadic colorectal tubular adenomas with different dysplasia (SCTA-D) or with cancerous changes (SCTA-Ca) by immunohistochemical staining method, meanwhile the expression of STAT3 at mRNA level was detected by in situ hybridization.

RESULTSImmunohistochemical staining results showed that the positive expression rate of STAT3 and p38 was 12.0%, 59.0%, 91.7% and 8.0%, 47.0%, 91.7% in normal colorectal mucosa (NCM), SCTA-D and SCTA-Ca, respectively, with a statistically significant difference of STAT3 and p38 expression among the SCTA-D, SCTA-Ca and NCM (P < 0.05). The expression of STAT3 and p38 was positively correlated with the degree of dysplasia from mild to severe SCTA-D (P < 0.05). In situ hybridization results showed that the positive expression rate of STAT3 at mRNA level in NCM, SCTA-D and SCTA-Ca was 8.00%, 51.8% and 100.0%, respectively, with a statistically significant difference among these either (P < 0.05). The positive expression of STAT3 at mRNA level was not only positively correlated with the degree of dysplasia (P < 0.05), but also with the expression of p38 (P < 0.05).

CONCLUSIONSTAT3 and p38 may be involved in the carcinogenesis of sporadic colorectal tubular adenoma.

Adenocarcinoma ; metabolism ; pathology ; Adenoma ; metabolism ; pathology ; Cell Transformation, Neoplastic ; metabolism ; Colorectal Neoplasms ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Intestinal Mucosa ; metabolism ; Precancerous Conditions ; metabolism ; pathology ; RNA, Messenger ; metabolism ; STAT3 Transcription Factor ; genetics ; metabolism ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism

Objective To analyze the status quo of patients with severe mental illness in Jinshan district, Shanghai, and provide sci-entific evidence for strengthening the prevention and treatment of them. Methods The data of severe mental illness until March 1st, 2016 were derived from the national database and analysis system, and were used for statistical analysis. Results A total of 4778 patients with severe mental illness were registered. Among them, 54.40% suffered from schizo-phrenia, patients aged 18 to 59 years old (67.73%) accounted for the vast majority, 86.44% only got junior high school education or below, 40.46% were unmarried or divorced, 76.50% patients choose outpatient department as a way to see doctor, and 15.11% patients did not take any treatment. Conclusion The prevention of severe mental illness has become the important gambit for this district. The proportion of patients choosing appropriate way to visit doctor is relatively low. The management of patients with severe men-tal diseases needs to be strengthened to promote the recovery of patients and social stability.

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

OBJECTIVE: To observe the changes of relative expression of myocardial various RNAs in rats died of different causes and their relationship with PMI. METHODS: The rat models were established in which the rats were sacrificed by broken neck, asphyxia, and hemorrhagic shock. Total RNAs were extracted from myocardium. The quantitative real time PCR was used to calculate threshold cycle values of RNAs including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-actin, inducible nitric oxide synthase (iNOS), hypoxia-inducible factor-1 (HIF-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and U6 small nuclear RNA (U6 snRNA) and to study the changes of the relative expressions of various indexes with PMI. RESULTS: U6 snRNA with stable expression level could be used as appropriate internal control. In the early PMI, the relative expression of GAPDH, HIF-1, iNOS, TNF-alpha, and IL-6 more characteristically increased in groups of asphyxia and hemorrhagic shock than in group of broken neck, but the quantity of beta-actin decreased in all groups. In the late PMI, all the relative expressions significantly declined in correlation with the degradation of RNA. CONCLUSION The characteristic changes of each RNA expression can be used as references to estimate PMI in deaths by different causes.
Actins ; Animals ; Cause of Death ; Cytokines/metabolism* ; Disease Models, Animal ; Enzymes/metabolism* ; Glyceraldehyde-3-Phosphate Dehydrogenases ; Myocardium/metabolism* ; Nitric Oxide Synthase Type II ; RNA/metabolism* ; RNA, Small Nuclear ; Rats ; Shock, Hemorrhagic ; Tumor Necrosis Factor-alpha

BACKGROUNDThe incidence of brain metastases in patients with breast cancer is approximately 10% - 16%, and survival after diagnosis of brain metastases is usually short. This study was designed to evaluate the risk factors associated with brain metastases in advanced breast cancer patients, with a view to help predict patient groups with high risk of brain metastases.

METHODSIn total, 295 patients with advanced breast cancer were evaluated. All patients were pathologically confirmed and metastatic lesions were confirmed pathologically or by imaging. All patients were examined at least once every 6 months with head CT or MRI. Patients showing symptoms underwent immediate inspection, and brain metastatic lesions were confirmed by head CT and/or MRI.

RESULTSAt a median follow-up of 12 months from the occurrence of metastases, brain metastases had occurred in 49 patients (16.6%). In our univariate analysis, variables significantly related to increased risk of brain metastases were hormone receptor-negative tumors, epidermal growth factor receptor 2 (HER2)-positive tumors, and multiple distant metastases. Patients with dominant tumor sites in soft tissue, or defined as Luminal A subtype, tended to have a lower risk of brain metastases than patients with visceral metastases, Luminal B subtype, triple-negative subtype or HER2-enriched subtype tumors.

CONCLUSIONSOur results strongly suggest that factors such as Luminal B, triple-negative, and HER2-enriched subtypes are high risk factors for brain metastases. These data, therefore, provide pivotal clinical evidence towards a comprehensive understanding of the risk factors of brain metastases in advanced breast cancer patients.

Adult ; Brain Neoplasms ; metabolism ; secondary ; Breast Neoplasms ; complications ; metabolism ; Female ; Humans ; Male ; Receptor, ErbB-2 ; metabolism ; Retrospective Studies ; Risk Factors

OBJECTIVETo biomechanically compare the stability of the short and long iliac screw fixation constructs in lumbo-iliac reconstruction.

METHODSSeven adult human embalmed cadavers (L(3)-pelvis) were used. Using posterior spinal fixation system, L(4)-S(1) pedicle screw fixation was performed. This was defined as intact state of the sacroiliac joint. After the intact test, total sacrum resection and L(4)-L(5)-pelvis reconstruction by pedicle screw and iliac screw with different lengths were performed as follow: short screw group (as the length of exceeding 2 mm over ischial notch) and long screw group (as the length of exceeding 2 mm over anterior inferior iliac spine). Using the 858 MTS material testing machine, biomechanical testing was performed under 800 N compression and 7 Nm torsion loading modes. At last, the axial pullout test of two iliac screws was executed. Construct stiffness in compression and torsion test, and maximum pullout force were analyzed.

RESULTSInsertion lengths of the short and long iliac screw were (70 +/- 2) mm and (138 +/- 4) mm respectively. The lumbo-pelvic reconstruction using short and long iliac screw, respectively restored 53.3% +/- 13.6% and 57.6% +/- 16.2% of the initial stiffness in compression testing, and respectively harvested 55.1% +/- 11.9% and 62.5% +/- 9.2% of the initial stiffness in torsion testing. No significant difference was detected between the two reconstructions (P > 0.05), however, the compressive and torsional stiffness of the two techniques were markedly less than the intact condition (P < 0.05). The maximum pullout strength of long iliac screw was significantly higher than short screw (P < 0.05).

CONCLUSIONSUnder the physical loading, lumbo-pelvic fixation construct using the short iliac screw may obtain mechanical stability comparable to that by long iliac screw. The short iliac screw is only the half of the long iliac screw by length, could reduce the implantation risk. However, the long iliac screw behaves greater axial pullout force, should be applied as far as possible in the osteoporosis patient. The lumbo-pelvic reconstruction utilizing any length of iliac screw is difficult to restore the local stability.

Adult ; Aged ; Biomechanical Phenomena ; Bone Screws ; Female ; Humans ; Ilium ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Pelvic Bones ; surgery ; Sacrum ; surgery ; Spinal Fusion ; methods

OBJECTIVETo build sub-endplate microcirculation disturbance animal model and to investigate the potential pathogenesis of intervertebral disc degeneration (IVDD).

METHODSTwenty four New Zealand white rabbits were divided into treatment group (Group A) and control group (Group B). In Group A, animals received endotoxin and corticosteroid application to build sub-endplate microcirculation disturbance animal model, validated by microthrombus staining. In Group B, animals were given no drug, but standard feeding. After 3 month, the extent of IVDD was evaluated by the water content, biochemistry analysis, and morphology.

RESULTSSub-endplate microthrombus staining confirmed the exist of microcirculation disturbance. The water content and biochemistry components content of disc in Group A were lower than those of disc in Group B, and IVDD was observed in morphology.

CONCLUSIONSub-endplate microcirculation disturbance can directly contribute to IVDD, the nutrients diffusion barrier is the potential pathogenesis of IVDD.

Animals ; Disease Models, Animal ; Female ; Intervertebral Disc ; blood supply ; metabolism ; pathology ; Male ; Microcirculation ; Rabbits ; Random Allocation ; Thrombosis ; complications ; metabolism ; pathology

OBJECTIVETo evaluate the efficacy of hBMP-4 gene modified tissue engineered bone graft in the enhancement of rabbit spinal fusion and find an ideal kind of substitute for the autograft bone.

METHODSRabbit BMSCs were cultured and transfected with AAV-hBMP-4 using different MOI value. The optimal MOI value were determined by observing cell's morphology change. BMSCs were then transfected with AAV-hBMP4 and AAV-EGFP respectively, following which the transfected cells were evenly suspended in a collagen sponge I, and implanted to either side of the L5,6 intertransverse spaces posterolateral in the New Zealand rabbits to induce spinal fusion. Fourteen rabbits were randomly divided into 2 groups. Group 1: AAV-hBMP-4 transfected BMSCs in the right side (hBMP-4 side) and autograft bone in the left side. Group 2: AAV-hBMP-4 transfected BMSCs in the right side (hBMP-4 side) and AAV-EGFP transfected BMSCs in the left side (EGFP side). Radiographs and three-dimensional CT of the spine, manual palpation, gross and histological examination of the fusion masses for all the animals were performed subsequent to animals having been sacrificed at 12 weeks after surgery.

RESULTSEvaluation has been taken in 12 New Zealand rabbits delivered into 2 groups which meet the criterion after operation. Eleven in 12 implemented sides involved hBMP-4 achieved bony fusion, to which 5 in 6 autografted sides was similar. But only 2 in 6 sides in EGFP-group achieved bony fusion meanwhile. Three-dimensional CT scan and palpation also evidenced the results. Bone formation was observed obviously on specimen both in hBMP4 sides and autografted ones. EGFP-group also got bony integration, but the quantity was small.

CONCLUSIONTissue-engineered bone graft constructed from application of hBMP4 is a fine substitute for autograft. Effective enhancement of bony integration in spinal fusion surgery has been evidenced in vivo.

Animals ; Bone Morphogenetic Protein 4 ; genetics ; Bone Regeneration ; Bone Substitutes ; Bone Transplantation ; methods ; Genetic Vectors ; Lentivirus ; genetics ; Male ; Myeloid Progenitor Cells ; Rabbits ; Random Allocation ; Spinal Fusion ; methods ; Stromal Cells ; Tissue Engineering ; Transfection