Objective To study the expression and the relation of vascular endothelial growth factor (VEGF)and matrix metal proteinase-2(MMP-2)in rectal cancer and evaluate their roles in rectal carcinogen- esis and development.Methods The expression of VEGF and MMP-2 in 52 cases of rectal cancer was de- tected by immunohistochemical SP technique.12 cases normal rectal tissue served as the control group.Re- suits The expression of VEGF in rectal carcinoma(67.3 %)was much higher than that in control group(P

BACKGROUND:Rapid and complete reperfusion has been widely adopted in the treatment of patients with acute myocardial infarction (AMI), but this process sometimes can cause severe reperfusion injury. This study aimed to investigate different patterns of post-conditioning in acute myocardial ischemia-reperfusion injury, and to detect the role of mitogen activated protein kinase (MAPK) during the injury. METHODS:Rats were randomly divided into five groups:sham group, reperfusion injury (R/I) group, gradually decreased reperfusion group (GDR group, 30/10-25/15-15/25-10/30 seconds of reperfusion/ischemia), equal reperfusion group (ER group, 20/20 seconds reperfusion/ischemia, 4 cycles), and gradually increased reperfusion group (GIR group, 10/30-15/25-25/15-30/10 seconds of reperfusion/ischemia). Acute myocardial infarction and ischemic post-conditioning models were established in the rats. Six hours after reperfusion, 3 rats from each group were sacrificed and myocardial tissues were taken to measure the expressions of phosphorylation of extracellular signal-regulated protein kinase (P-ERK), phosphorylated c-Jun N-terminal kinase (P-JNK), mitogen-activated protein kinase p38 (p38 MAPK), tumor necrosis factor-α (TNF-α), caspases-8 in the myocardial tissue, and cytochrome c in the cytosol using Western blot. Hemodynamics was measured at 24 hours after reperfusion, the blood was drawn for the determination of cardiac enzymes, and the heart tissue was collected for the measurement of apoptosis using TUNEL. One-way analysis of variance and the Q test were employed to determine differences in individual variables between the 5 groups. RESULTS:Three post-conditioning patterns were found to provide cardioprotection (P<0.05) compared with R/I without postconditioning. GIR provided the best cardioprotection effect, followed by ER and then GDR. Apoptotic index and serum marker levels were reduced more significantly in GIR than in ER (P<0.05). The enhanced cardioprotection provided by GIR was accompanied with significantly increased levels of P-ERK 1/2 (1.82±0.22 vs. 1.54±0.32,P<0.05), and lower levels of p-JNK, p38 MAPK, TNF-α, caspase-8, caspase-9 and cytochrome in the cytoplasm (P<0.05), compared with ER. The infarct size was smaller in the GIR group than in the ER group, but this difference was not significant (16.30％±5.22％ vs. 20.57％±6.32％,P<0.05). Allthe measured variables were improved more significantly in the GIR group than in the GDR group (P<0.05). CONCLUSION:Gradually increased reperfusion in post-conditioning could attenuate reperfusion injury more significantly than routine method, thereby the MAPK pathway plays an important role in this process.

OBJECTIVETo compare the effects of carvedilol, metoprolol and propranolol on myocardial gap junction (GJ) structure in rat with myocardial ischemia and reperfusion injury.

METHODSRats were divided randomly into five groups: sham operation group (SO), myocardial ischemia and reperfusion group (IR), IR + carvedilol group (CV), IR + metoprolol group (MT), and IR + propranolol group (PP). The left anterior descending branch was ligated for 30 minutes and reperfused for 4 hours (IR). After 4 h reperfusion, the distribution and composition of gap junctional connexin 43 (CX43) were observed by immunofluorescence and laser scanning confocal microscopy (LSCM), and the quantification of CX43 was measured by LSCM.

RESULTCompared with SO group, IR resulted in abnormal distribution and composition of CX43-GJ and the impairment of CX43-GJ was significantly attenuated by CV, MT and PP treatments with the best effect observed in CV group (P<0.05 vs. MT and PP).

CONCLUSIONThese results suggest that beta-blockers, especially, carvedilol, could significantly attenuate IR induced CX43-GJ impairment.

Adrenergic beta-Antagonists ; pharmacology ; Animals ; Connexin 43 ; metabolism ; Disease Models, Animal ; Gap Junctions ; drug effects ; Male ; Myocardial Reperfusion Injury ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley

Ibuprofen/ethyl-cellulose (EC)-polyvinylpyrrolidone (PVP) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading as the main evaluation index, orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles. The experiments such as encapsulation efficiency, particle size distribution, electron microscope analysis, infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 40 degrees C, crystallization pressure 12 MPa, PVP concentration 4 mgmL(-1), and CO2 velocity 3.5 Lmin(-1). Under the optimal conditions, the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%, and the average particle size of the particles was 27.621 microm. IR and DSC analysis showed that PVP might complex with EC. The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect. Experiment results showed that, ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.
Calorimetry, Differential Scanning ; Carbon Dioxide ; chemistry ; Cellulose ; administration & dosage ; analogs & derivatives ; chemistry ; Crystallization ; Delayed-Action Preparations ; Drug Carriers ; Drug Compounding ; Ibuprofen ; administration & dosage ; chemistry ; Microscopy, Confocal ; Particle Size ; Povidone ; administration & dosage ; chemistry ; Solubility ; Spectrophotometry, Infrared ; Technology, Pharmaceutical ; methods

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC₅₀ = 0.33 μmol·L^-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L^-1, 21.2% inhibition at 1 μmol·L^-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

Objective:To investigate the clinical significance of TP53 allelic state in patients with myelodysplastic syndromes(MDS).Methods:The clinical data of 858 MDS patients who underwent second-generation sequencing(NGS)testing in the First Affiliated Hospital of Soochow University from January 2019 to December 2021 were retrospectively analyzed.Results:The median age of the patients was 52 years old,and median follow-up time was 23.8(0.4-109.6)months.Four hundred and one patients(46.7％)had at least one chromosomal abnormality,including 106 complex karyotypes and 78 monosomal karyotypes.A total of 103 cases of TP53 mutations were identified,with a mutation rate of 12％.Compared with TP53 wild-type,various types of chromosomal abnormalities were significantly more common in patients with TP53 mutations(all P＜0.001).Patients with TP53 mutations had lower hemoglobin levels,lower platelet counts and higher percentage of bone marrow primitive cell compared with TP53 wild type(all P＜0.05),and significantly shorter overall survival(OS).Among 97 evaluable patients,33 cases(34％)were mono-allelic TP53 mutation,while 64 cases were bi-allelic TP53 mutation.Patients in bi-allelic TP53 mutation subgroup had a higher proportion of chromosomal abnormalities and a lower number of co-mutations compared with mono-allelic TP53 mutation.The median OS was 33.6 months in patients with mono-allelic state and only 11.4 months in patients with bi-allelic state(HR=2.138,95％CI:1.053-4.343,P＞0.05).Median OS was not reached in TP53 wild-type patients,and there was a significant difference in OS among TP53 wild-type,mono-allelic and bi-allelic TP53 mutation patients(P＜0.001).Multivariable Cox regression analysis showed that bi-allelic TP53 was an independent predictor of poor outcomes(HR=2.808,95％CI:1.487-5.003,P=0.001),while mono-allelic TP53 mutation and wild-type TP53 were not.Conclusion:Patients with TP53 mutations have a poor prognosis,and bi-allelic TP53 mutations have a worse prognosis compared with mono-allelic TP53 mutations and independently affect the prognosis of MDS patients.

OBJECTIVETo investigate the changes of thyroxin and monocyte human leukocyte antigen-DR expression in senior patients with sepsis and explore their clinical significance.

METHODSAccording to the 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions, 125 senior patients with sepsis free of thyroid conditions were divided into non-severe sepsis group (n=86) and severe sepsis group (n=39), with another 30 healthy subjects as the control. Thyroid function was assayed by chemoluminescence method in these patients and monocyte HLA-DR expression was determined by flow cytometry.

RESULTSCompared with the control group and non-severe sepsis cases, the levels of free T3 (FT3), free T4 (FT4), T3, T4 and monocyte HLA-DR expression were significantly lower in severe sepsis cases (P<0.05), but the levels of thyroid stimulating hormone (TSH) were comparable between the 3 groups (P>0.05). The non-severe sepsis cases showed significantly lower levels of FT3, FT4, T3, T4, TSH and monocyte HLA-DR expression than the control group (P<0.05). In severe sepsis group, the levels of FT3, FT4, T3, T4 and monocyte HLA-DR expression showed significant differences between the fatal cases and surviving cases (P<0.05).

CONCLUSIONThe levels of thyroxin and monocyte human leukocyte antigen-DR expression are obviously lower in senior patients with severe sepsis, and their detection may well indicate the severity of the condition and help make prognostic judgment.

Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; HLA-DR Antigens ; blood ; immunology ; Humans ; Male ; Monocytes ; metabolism ; Pneumonia ; complications ; Sepsis ; blood ; etiology ; immunology ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

OBJECTIVETo evaluate the efficacy of preoperative radiochemotherapy and investigate the influencing factors in rectal cancer.

METHODSFifty-three patients with locally advanced rectal cancer were treated with radiochemotherapy before surgery. Three-field technique of radiation therapy was administered with 46 Gy, 2 Gy per fraction, five times a week. Two cycles of chemotherapy were carried out at day 1, 2 and day 21, 22 during the radiation course. Surgery was performed 4-6 weeks after the radiochemotherapy. Response of preoperative radiochemotherapy was evaluated in all the patients by endoscopic ultrasonography (EUS), spiral computed tomography (SCT) and pathology. Influencing factors of the efficacy of radiochemotherapy were evaluated by univariate and Logistic analysis.

RESULTSUnivariate analysis revealed that tumor size and histological grading were associated with the efficacy of preoperative radiochemotherapy. Logistic regression analysis showed that only tumor size was the significant predictive factor for response to preoperative radiochemotherapy. All patients underwent surgical resection after preoperative radiochemotherapy. The tumor was reduced by an average of 32.1%. T-level down-staging was 64.2%. Nodal negativity was 58.1%. Complete pathologic remission occurred in 11 patients.

CONCLUSIONSPreoperative radiochemotherapy can shrink the primary tumor and decrease lymph node metastasis rate. Patient with small tumor may have better response to preoperative radiochemotherapy.

Adult ; Aged ; Chemotherapy, Adjuvant ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Radiotherapy, Adjuvant ; Rectal Neoplasms ; drug therapy ; radiotherapy ; therapy ; Treatment Outcome ; Young Adult

OBJECTIVETo observe the characteristics and difference of gene expression in the pituitary adenomas and para-tumor normal pituitary tissues.

METHODSUsing serial analysis of gene expression (SAGE), two SAGE libraries were generated. Forty clones from each SAGE library were sequenced, and the results were analyzed by SAGE2000 software and compared with the SAGE map at NCBI.

RESULTSA total of 655 gene tags, representing 43 genes, were extracted from the 40 sequence files of the para-tumor normal pituitary tissues and 737 gene tags, representing 53 genes, were extracted from the 40 sequence files of the pituitary adenomas. Of these tags, 13 were not reported before. The genes related to pituitary hormone secretion and energy metabolism were highly expressed in the two kinds of tissues. Some growth factors and cytokines were also expressed, including those involved in the immunological system. But there were also much difference of gene expression in the two tissues. Thirty-one and five tags were only detected in para-tumor normal pituitary tissues and pituitary adenomas, respectively.

CONCLUSIONSGenes involved in hormones secretion and energy metabolism were highly expressed in the pituitary adenomas and para-tumor normal pituitary tissues. Many growth factors and cytokines were also expressed in pituitary. There was also much difference of gene expression in the two kinds of tissues. SAGE can be used not only in understanding the quantity information of gene expression, but also in finding new genes.

Adenoma ; genetics ; metabolism ; Base Sequence ; Cloning, Molecular ; Expressed Sequence Tags ; Gene Expression ; Gene Expression Profiling ; methods ; Gene Expression Regulation, Neoplastic ; Gene Library ; Humans ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis ; Pituitary Gland ; metabolism ; Pituitary Neoplasms ; genetics ; metabolism

The aim of the study was to determine the expression of cytidine deaminase (CDD) gene in bone marrow cells from patients with acute leukemia (AL) and evaluate the relationship between CDD expression and clinical feature. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used for detection of expression level of CDD mRNA in bone marrow cells from 83 patients with acute leukemia and from 15 healthy peoples as control. CDD/beta-actin ratio >or= 0.5 was considered to be positive. The results showed that expression levels of CDD of 31 previously untreated patients were higher than those of 23 cases of AL in complete remission and of normal controls. Expression levels of CDD of 29 relapse/refractory patients were also higher than those of 23 AL patients in complete remission and of normal subjects. The expression levels of CDD in relapse/refractory ALL were higher than those in AML while expression levels of CDD were not correlated with the outcome of therapy. It is concluded that the level of CDD mRNA expression varies at the different stage of acute leukemia. The expression level of CDD seems not to be a prognostic factor.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow Cells ; enzymology ; Cytidine Deaminase ; genetics ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; enzymology ; genetics ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; enzymology ; genetics ; RNA, Messenger ; genetics ; metabolism ; Remission Induction ; Reverse Transcriptase Polymerase Chain Reaction