OBJECTIVE:To investigate Smad3 and Smad7 expression in cardiac tissues in myocardial infarction (MI) rats and the effect of simvastatin (SIM) on expression of Smads.METHODS:36 rats were randomized into SIM (40 mg?kg-1,n=12) group,MI group (normal saline,n=12) and SHAM group (normal saline,n=12).Rats in first two groups were induced MI model.Rats of 3 groups were sacrificed after four weeks administration.The mRNA expressions of Smad3 and Smad7 in non-infarction regions were measured by RT-PCR.Smad3 and Smad7 protein expressions were measured by Western blotting assay.RESULTS:As compared with SHAM group,the expressions of Smad3 in MI group and SIM group were increased while the expressions of Smad7 were decreased.As compared with MI group,the mRNA expression and protein expression of Smad3 in SIM group was decreased while that of Smad7 increased (P

Objective To study the transfection efficiency, protein expression, and effect of adenovirus-mediated transfection on microvascular endothelial cells transfected by angiopoietin-related protein 2(Ad. ARP2)gene. Methods Mice coronary microvascular endothelial cells(CMECs) were isolated, cultured and transferred by Ad-ARP2. The transfection efficiency and cellular toxicity of adenovirus vector to CMECs were detected by immunofluorescence staining. Expression of Ad. ARP2 in CMECs and the secreted materials in culture medium were measured by Western blot and ELISA and compared among groups of Ad. ARP2, Ad. null, and PBS control. Vascular endothelial cells were incubated with conditional medium containing secreted ARP2, and effects on cells sprouting were observed in matrigel. Results Adenovirus-transfected CMECs showed a very high efficiency. When multiplicity of infection (MOD was 200, the transfection efficiency was 93. 5% ,and no harmful effect on CMECs growth was found. When CMECs were transfected with Ad. ARP2, there was a high ARP2 expression, which was significantly different from that with Ad. Null or PBS. The conditional medium containing ARP2 had an excellent ability to stimulate sprout of CMECs which phenomenon could not be seen in the control groups. Conclusions Adenovirus vector can be transferred into CMECs efficiently and safely. Ad. ARP2 gene transfection allows a high transient expression, and the expression products can stimulate the sprout of microvascular endothelial cells in vitro very well.

Anal Canal/surgery* ; Anorectal Malformations ; Constriction ; Fecal Incontinence ; Humans ; Rectal Prolapse

The different biological functions were studied in mouse bone marrow-derived endothelial progenitor cells isolated by differential time attachment to obtain the optimal adherent time in this study. Density gradient centrifugation-isolated bone marrow mononuclear cells were seeded on the fibronectin-coated dish. The 1-day cultured unattached cells were seeded on the second dish for 2 more days. Then unattached cells in the second dish were seeded on the third dish. The cells on 3 dishes were defined as 1-day adherent cells, 3-day adherent cells and 3-day unattached cells, respectively. After 20-day culture, the biological functions, such as the percentage of biomarkers, the ability of adhesion, and the ability of forming tubes in vitro were analyzed. The results showed that the percentages of positive CD34, FLK-1, and CD34/FLK-1 expressions in 1-day attached cells were significantly increased compared to those in the 3-day adherent or unattached cells (P < 0.01), which showed the strongest adhesion ability. The expression of eNOS in 1- or 3-day adherent cells was significantly higher than that in 3-day unattached cells (P < 0.01). The expression of VEGF in 3-day adherent cells was significantly higher than that in 1-day adherent cells or 3-day unattached cells (P < 0.01). These results suggest the biological functions of 1-day adherent cells are significantly stronger than that of 3-day adherent or unattached cells. VEGF expression in 3-day adherent cells is higher than that in 1-day adherent cells or 3-day unattached cells. The expression of eNOS in 1-day adherent cells or 3-day adherent cells is higher than that in 3-day unattached cells. The optimal adherent time to obtain mouse bone marrow-derived endothelial progenitor cells is 1-3 d.
Animals ; Bone Marrow Cells ; cytology ; Cell Culture Techniques ; methods ; Cell Differentiation ; Cell Separation ; methods ; Cells, Cultured ; Endothelial Cells ; cytology ; metabolism ; Leukocytes, Mononuclear ; cytology ; Male ; Mice ; Mice, Inbred C57BL ; Nitric Oxide Synthase Type III ; metabolism ; Stem Cells ; cytology ; metabolism ; Time Factors ; Vascular Endothelial Growth Factor A ; metabolism

Purpose To investigate the expression and the clinical significances of SEL1L and BCL-2 in 123 cases of diffuse large B cell lymphoma (DLBCL) and cell line SUDHL-4, LY-10. Methods Immunohistochemistry staining for SEL1L was performed in 123 DLBCL and 60 reactive lymphoid hyperplasia (RLH), and also BCL-2 protein in 123 DLBCL. Immunocytochemistry staining and Western blot analysis for SEL1L protein were used in SUDHL-4 and LY-10. Results The high expression rate of SEL1L was 69.9％ in 123 DLBCL, which was significantly higher than that in 60 RLH (25.0％ ). The expression of SEL1L protein in DLBCL was not related to clinic pathological parameters. The positive rate of BCL-2 was 83.7％ in123 DLBCL. The expression of BCL-2 protein was correlated with immunophenotyping, primary location, and Ann Arbor stage. The expression of SEL1L protein was positively correlated with that of BCL-2 protein in DLBCL (r=0.227, P＜0.05). SEL1L protein was also detected in SUDHL-4 and LY-10 cell lines. Conclusion The SEL1L protein may play an important role in the carcinogenesis of DLBCL, and may be associated with BCL-2.

OBJECTIVE: To analyze the difference in the gene expression, amino acid and carnitine levels in the cervical secretions between the endometria of pre-receptive and receptive stages, with an aim to provide clues for identifying new molecular markers for endometrial receptivity. METHODS: Fifty nine infertile women treated at the Department of Reproductive Medicine of Linyi People's Hospital from January 6, 2020 to January 31, 2022 were selected as as the study subjects, which were matched with 3 pairs (6 cases) of infertile women preparing for embryo transfer based on factors such as age, body mass index, and length of infertility. Endometrial tissue samples were collected for gene transcription and expression analysis. Twenty five women who had become pregnant through assisted reproductive technology were selected as the control group, and 28 non-pregnant women receiving ovulation monitoring at the Outpatient Department were enrolled as the case group. Status of endometrial receptivity was determined by ultrasonography. In the former group, endometrial tissues were sampled for sequencing, and GO and KEGG database enrichment analysis of differentially expressed genes was carried out. In the latter group, cervical secretions were collected, and amino acid and carnitine levels were measured by mass spectrometry. Statistical analysis was carried out using rank sum test, t test and chi-square test with SPSS v25.0 software. RESULTS: No difference was found in the clinical data of the patients with regard to age, body mass index, infertility years, AMH, FSH, LH, E2, and type of infertility. Compared with the receptive endometrial tissues, there were 100 significantly up-regulated genes and 191 significantly down-regulated genes in the pre-receptive endometrial tissue, with the most significantly altered ones being HLA-DRB5 and MMP10. The biological processes, molecular functions and pathways enriched by more differentially expressed genes in GO and KEGG were mainly immune regulation, cell adhesion and tryptophan metabolism. Analysis of secretion metabolism also revealed a significant difference in the levels of amino acids and carnitine metabolites between the two groups (P < 0.05), in particular those of Alanine, Valine, 3-hydroxybutyrylcarnitine (C4OH) + malonylcarnitine (C3DC)/captoylcarnitine (C10). CONCLUSION A significant difference has been discovered in the levels of gene transcription and protein expression in the endometrial tissues from the pre-receptive and receptive stages. The levels of amino acids and carnitine, such as Alanine, Valine, 3-hydroxybutyryl carnitine (C4OH)+malonyl carnitine (C3DC)/caproyl carnitine (C10), may be associated with the receptive status of the endometrium, though this need to be verified with larger samples.
Pregnancy ; Humans ; Female ; Infertility, Female/genetics* ; Endometrium/metabolism* ; Amino Acids/metabolism* ; Gene Expression ; Carnitine ; Alanine/metabolism* ; Valine/metabolism*

OBJECTIVETo compare the pathologic diagnosis and immunohistochemistry of small cell malignant tumors (SCMT) of bone using both core needle biopsy and surgical specimen.

METHODSSeventy-seven cases of SCMT with core needle biopsies and surgical specimens available were respectively analyzed by histologic examination and immunohistochemical study, with literature review.

RESULTSThe male-to-female ratio was 48:29. The age of the patients ranged from 6 to 73 years. The tumors studied included Ewing sarcoma/PNET (n = 38), myeloma (n = 23), lymphoma (n = 10), small cell osteosarcoma (n = 2), small cell carcinoma (n = 2) and mesenchymal chondrosarcoma (n = 2). The tumors involved limbs, axial skeleton and flat bones. Microscopically, the tumors shared similar histology, with small round cells and spindly cells arranged in diffuse sheets. The pathologic diagnosis by core needle biopsies correlated with that by surgical specimens in 84.4% (65/77) of the cases.

CONCLUSIONSSCMT represents a heterogeneous group of malignancy. Correlations with clinicoradiologic findings and application of ancillary investigations including immunohistochemistry and molecular study are important for definitive diagnosis. Pathologic diagnosis using core needle biopsies shows good results and provides useful information for surgical planning.

12E7 Antigen ; Adolescent ; Adult ; Aged ; Antigens, CD ; metabolism ; Biopsy, Large-Core Needle ; Bone Neoplasms ; diagnosis ; metabolism ; pathology ; Carcinoma, Small Cell ; diagnosis ; metabolism ; pathology ; Cell Adhesion Molecules ; metabolism ; Child ; Female ; Humans ; Lymphoma ; diagnosis ; metabolism ; pathology ; Male ; Middle Aged ; Neuroectodermal Tumors, Primitive, Peripheral ; diagnosis ; metabolism ; pathology ; Oncogene Proteins, Fusion ; metabolism ; Osteosarcoma ; diagnosis ; metabolism ; pathology ; Plasmacytoma ; diagnosis ; metabolism ; pathology ; Proto-Oncogene Protein c-fli-1 ; metabolism ; RNA-Binding Protein EWS ; metabolism ; Retrospective Studies ; Sarcoma, Ewing ; diagnosis ; metabolism ; pathology ; Vimentin ; metabolism ; Young Adult

BACKGROUNDThe optimal ventilated status under total intravenous or inhalation anesthesia in neurosurgical patients with a supratentorial tumor has not been ascertained. The purpose of this study was to intraoperatively compare the effects of moderate hyperventilation on the jugular bulb oxygen saturation (SjO 2 ), cerebral oxygen extraction ratio (O 2 ER), mean arterial blood pressure (MAP), and heart rate (HR) in patients with a supratentorial tumor under different anesthetic regimens.

METHODSTwenty adult patients suffered from supratentorial tumors were randomly assigned to receive a propofol infusion followed by isoflurane anesthesia after a 30-min stabilization period or isoflurane followed by propofol. The patients were randomized to one of the following two treatment sequences: hyperventilation followed by normoventilation or normoventilation followed by hyperventilation during isoflurane or propofol anesthesia, respectively. The ventilation and end-tidal CO 2 tension were maintained at a constant level for 20 min. Radial arterial and jugular bulb catheters were inserted for the blood gas sampling. At the end of each study period, we measured the change in the arterial and jugular bulb blood gases.

RESULTSThe mean value of the jugular bulb oxygen saturation (SjO 2 ) significantly decreased, and the oxygen extraction ratio (O 2 ER) significantly increased under isoflurane or propofol anesthesia during hyperventilation compared with those during normoventilation (SjO 2 : t = -2.728, P = 0.011 or t = -3.504, P = 0.001; O 2 ER: t = 2.484, P = 0.020 or t = 2.892, P = 0.009). The SjO 2 significantly decreased, and the O 2 ER significantly increased under propofol anesthesia compared with those values under isoflurane anesthesia during moderate hyperventilation (SjO 2 : t = -2.769, P = 0.012; O 2 ER: t = 2.719, P = 0.013). In the study, no significant changes in the SjO 2 and the O 2 ER were observed under propofol compared with those values under isoflurane during normoventilation.

CONCLUSIONSOur results suggest that the optimal ventilated status under propofol or isoflurane anesthesia in neurosurgical patients varies. Hyperventilation under propofol anesthesia should be cautiously performed in neurosurgery to maintain an improved balance between the cerebral oxygen supply and demand.

Adolescent ; Adult ; Aged ; Anesthetics, Inhalation ; Anesthetics, Intravenous ; Arterial Pressure ; physiology ; Blood Gas Analysis ; Craniotomy ; methods ; Female ; Heart Rate ; physiology ; Humans ; Hyperventilation ; chemically induced ; physiopathology ; Isoflurane ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Propofol ; administration & dosage ; therapeutic use ; Young Adult

New Chemical Entities (NCEs) development is a systematic long-term project that involves multiple disciplines. The translation research will help to build an advanced R&D system from the basic laboratory research, preclinical studies and clinical evaluation to clinical application of drug, for the purpose of shortening the R&D cycle and accelerate the launch of new drugs. In new drug R&D and its clinical application, drug disposition (absorption, distribution, metabolism, excretion, ADME) properties are important criteria for assessing drug-likeness of candidates. ADME evaluation of NCEs plays an important role in the translation research throughout innovative drug R&D process. Therefore, ADME evaluation at the early stage of drug design and development will be helpful to improve the success rate and reduce costs, and further access to safe, effective drugs.
Absorption ; Biological Transport ; Drug Design ; Drug Evaluation, Preclinical ; Pharmaceutical Preparations ; chemistry ; metabolism ; Pharmacokinetics ; Tissue Distribution ; Translational Medical Research