Aim To investigate the effects of Ang Ⅱ receptor antagonist irbesartan on the expressions of connective tissue growth factor(CTGF) and membrane-type 1 matrix metalloproteinase(MT1-MMP) in high glucose-cultured rat glomerular mesangial cells(GMCs).Methods High concentration glucose and irbesartan were used to stimulate the cultured rat GMCs in vitro.The mRNA and protein expressions of CTGF and MT1-MMP were detected with semi-quantitative RT-PCR and Western blot.The secreted collagen Ⅳ in the supernatants of the GMCs was detected by enzyme-linked immunoadsorbent assay(ELISA).Results Compared with control group,the expressions of CTGF were continuously increased in GMCs under high concentration glucose medium;otherwise the mRNA and protein levels of MT1-MMP in GMCs were decreased in a time-dependent manner at the same time.These changes were accompanied by increased secretion of collagen Ⅳ.Irbesartan could inhibit those changes induced by high glucose.Conclusions High glucosecould induce the expression of CTGF and inhibit the expression of MT1-MMP in GMCs.Irbesartan could inhibit the secretion of ECM in GMCs under high concentration glucose medium,partly by regulating the expressions of CTGF and MT1-MMP.

This study was aimed to investigate the effect of polypeptide extract from scorpion venom (PESV) on PI3K, p-Akt signal protein regulating K562 cell apoptosis and its mechanism. The K562 cells were cultured with PESV for different time, the cell growth curve was determined by MTT method, the levels of PI3K and p-Akt proteins were detected by Western blot. The results showed that as compared with control group, the apoptosis rate of K562 cells treated with PESV increased, the levels of PI3K and p-Akt expression decreased. It is concluded that the PESV inhibits the proliferation and promotes the apoptosis of K562 cells probably through suppressing the expression of PI3K and p-Akt signal proteins.
Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Humans ; K562 Cells ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Scorpion Venoms ; pharmacology ; Signal Transduction ; drug effects

OBJECTIVETo re-evaluate the effects of different treatments to prevent from phlebitis induced by Chansu injection.

METHODPatients treated with Chansu injection were divided randomly into 4 groups with 50 per group, control group, the magnesium sulfate group, phentolaminum group, and anisodamine group. Patients in the control group only received the routine nursing treatment, and patients in the various experiment group received different interventions. The comparison was made in the morbidity and the starting time of occurrence of phlebitis, the severity of pain, duration of pain.

RESULTThe morbidity of phlebitis was 8%, 8%, 6% respectively. The starting time of phlebitis occurrence was (21 +/- 9.31) , (22.34 +/- 10.15), (20.19 +/- 11.23) h, respectively. The NRS of pain was (4. 15 +/- 1.03), (3.26 +/- 1.17), (4.32 +/- 1.36), respectively. The duration time of pain was (4.05 +/- 1.21), (3.37 +/- 1.17), (3.19 +/- 1.67) d, respectively. In control group, the morbidity of phlebitis, the starting time of occurrence of phlebitis, the severity of pain, duration of pain was 24%, (17 +/- 6.32) h, (6.58 +/- 1.29), (5.32 +/- 1.12) d, respectively. As compared with the control group, a significance difference was found between every group in three test groups and control group respectively (P<0.05).

CONCLUSIONThe morbidity and the starting time of occurrence of phlebitis, the severity of pain, duration of pain was significantly reduced respectively by external appication of magnesium sulfate, anisodamine, and intravenous drip infusion of phentolaminum.

Adult ; Aged ; Aged, 80 and over ; Bufanolides ; adverse effects ; Female ; Humans ; Infusions, Intravenous ; Magnesium Sulfate ; therapeutic use ; Male ; Middle Aged ; Morbidity ; Phentolamine ; administration & dosage ; Phlebitis ; chemically induced ; prevention & control ; Solanaceous Alkaloids ; therapeutic use ; Time Factors

This study was purposed to establish and identify the model of extramedullary infiltration of CML-NOD/SCID mice. 24 mice were irradiated with 270 cGy of (137)Cs and absorbed dose rate 80 cGy/min, and were randomly divided into test group I, test group II and control group. The mice in test group I and test group II were injected with 5×10(6) and 1×10(7) K562 cells per mouse respectively, the mice in control group were injected with 0.2 ml of normal saline. The general situation and survival time of these mice were monitored, the extramedullary infiltration of leukemia cells was detected by histopathology examination and RT-PCR. The results indicated that at 4 - 8 weeks after injection, all the mice of group I and group II displayed extramedullary infiltration, suggesting that CML/NOD-SCID model was successfully established. It is concluded that the model of extramedullary infiltration of CML/NOD-SCID mice can be established by injection K562 cells into caudal vein, and can be confirmed by histopathologic examination and detection of BCR-ABL fusion gene using RT-PCR.
Animals ; Disease Models, Animal ; Female ; Humans ; Injections, Intravenous ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Transplantation ; Tail ; blood supply

Abstract: The new generation of artificial intelligence technology, represented by deep learning, has emerged as a crucial driving force in the advancement of new drug research and development. This article creatively proposes a workflow named “Molecular Factory” for the design and optimization of drug molecules based on artificial intelligence technology. This workflow integrates intelligent molecular generation models, high-performance molecular docking algorithms, and accurate protein-ligand binding affinity prediction methods. It has been integrated as a core module into DrugFlow, a one-stop drug design software platform, providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds. Utilizing the “Molecular Factory” module, we conducted the research of second-generation inhibitors against Menin that can combat drug resistance. Through the integration of computational and experimental approaches, we rapidly identified multiple promising compounds. Among them, compound RG-10 exhibited the IC50 values of 9.681 nmol/L, 233.2 nmol/L, and 40.09 nmol/L against the wild-type Menin, M327I mutant, and T349M mutant, respectively. Compared to the positive reference molecule SNDX-5613, which has entered Phase II clinical trials, RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants. These findings fully demonstrate the unique advantages of the "Molecular Factory" technology in practical drug design and development scenarios. It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures, holding significant value and profound implications for advancing new drug discovery.

OBJECTIVETo evaluate the effects and mechanism of radiation-sterilized allogeneic bone sheets in inducing vertebral plate regeneration after laminectomy in sheep.

METHODSTwelve adult male sheep (aged 1.5 years and weighing 27 kg on average) provided by China Institute for Radiation Protection underwent L3-4 and L4-5 laminectomy. Then they were randomly divided into two groups: Group A (n=6) and Group B (n=6). The operated sites of L4-5 in Group A and L3-4 in Group B were covered by "H-shaped" freeze-drying and radiation-sterilized allogeneic bone sheets (the experimental segments), while the operated sites of L3-4 in Group A and L4-5 in Group B were uncovered as the self controls (the control segments). The regeneration process of the vertebral plate and the adhesion degree of the dura were observed at 4, 8, 12, 16, 20 and 24 weeks after operation. X-ray and CT scan were performed in both segments of L3-4 and L4-5 at 4 and 24 weeks after operation.

RESULTSIn the experimental segments, the bone sheets were located in the anatomical site of vertebral plate, and no lumbar spinal stenosis or compression of the dura was observed. The bone sheets were absorbed gradually and fused well with the regenerated vertebral plate. While in the control segments, the regeneration of vertebral plate was not completed yet, the scar was inserted into the spinal canal, compressing the dura and the spinal cord, and the epidural area almost disappeared. Compared with the control segments, the dura adhesion degree in the experimental regenerated segments was much milder (P less than 0.01), the internal volume of the vertebral canal had no obvious change and the shape of the dura sack remained well without obvious compression.

CONCLUSIONSFreeze-drying and radiation-sterilized allogeneic bone sheets are ideal materials for extradural laminoplasty due to their good biocompatibility, biomechanical characteristics and osteogenic ability. They can effectively reduce formation of post-laminectomy scars, prevent recurrence of post-laminectomy spinal stenosis, and induce regeneration of vertebral plates.

Animals ; Bone Transplantation ; methods ; Laminectomy ; methods ; Regeneration ; Sheep ; Spinal Stenosis ; prevention & control ; Spine ; physiology ; Transplantation, Homologous

OBJECTIVESTo compare the efficacy and feasibility between intracoronary and hypodermic injection of granulocyte colony-stimulating factor (G-CSF) on improving cardiac function in a Swine model of chronic myocardial ischemia.

METHODSEighteen Swine underwent placement of ameroid constrictor on left circumflex coronary artery. The presence of myocardial ischemia was verified at four weeks after the operation, and the animals were then randomly assigned into three groups (n = 6 each): (1) administration of vehicle (control), (2) hypodermic injection of G-CSF (5 microgxkg(-1)x;d(-1)) for five days (IH), and (3) intracoronary injection of a bonus G-CSF (60 microg/kg) (IC). Coronary angiogram, cardiac MRI, and (18)F-FDG-SPECT/(99m)Tc-SPECT (DISA-SPECT) measurements were performed at pre-administration and at 4 weeks post administration. Global heart function such as left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVSDV) and left ventricular ejection fraction (LVEF), myocardial perfusion, myocardial viability and myocardial infarct area were evaluated. Myocardial vWF, Bcl-2 and Bax expressions were detected by Western blot and RT-PCR.

RESULTSMRI data showed that left ventricular dilation and dysfunction were similarly prevented in IH and IC G-CSF treated animals at eight weeks after the operation. SPECT revealed that both IH and IC G-CSF equally improved the regional contractility of chronic myocardial ischemia and increased myocardial viability. Myocardial infarct size was also reduced after both G-CSF treatments as detected by MRI. Intracoronary injection of G-CSF did not lead to angiogenesis in other organs. G-CSF treatments were also associated with a significant reduction in myocardial apoptosis and significant increase in angiogenesis.

CONCLUSIONSBoth intracoronary and hypodermic injection of G-CSF were safe and feasible and could equally improve cardiac function and increase angiogenesis in this Swine model of chronic myocardial ischemia.

Animals ; Coronary Vessels ; Disease Models, Animal ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Male ; Myocardial Ischemia ; therapy ; Recombinant Proteins ; Swine

Acute myocardial infarction is a rare but potentially lethal complication of systemic lupus erythematosus. There are several proposed mechanisms for acute myocardial infarction in lupus patients: atherosclerosis and endothelial injury leading to plaque rupture, coronary vasculitis and inflammation of the vessel wall causing aneurismal dilatation or spasm, and acute thrombosis and embolism. We report a-37-year-old man with systemic lupus erythematosus who developed myocardial infarction twice. Potential mechanisms for acute myocardial infarction for this patient are discussed in this report.
Atherosclerosis ; Dilatation ; Embolism and Thrombosis ; Humans ; Inflammation ; Lupus Erythematosus, Systemic* ; Male* ; Myocardial Infarction* ; Percutaneous Coronary Intervention* ; Rupture ; Spasm ; Vasculitis

BACKGROUNDAcute kidney injury (AKI) is considered as a common and significant complication following abdominal aortic aneurysm (AAA) repair. This study aimed to assess the associated risk factors of AKI in the critically ill patients undergoing AAA repair and to evaluate the appropriate AKI management in the specific population.

METHODSWe retrospectively examined data from all critically ill patients undergoing AAA repairs at our institution from April 2007 to March 2012. Multivariable analysis was used to identify factors associated with postoperative AKI, which was defined by risk, injury, failure, loss and end-stage (RIFLE) kidney disease criteria. The goal-directed hemodynamic optimization (maintenance of optimal hemodynamics and neutral or negative fluid balance) and renal outcomes were also reviewed.

RESULTSOf the 71 patients enrolled, 32 (45.1%) developed AKI, with 30 (93.8%) cases diagnosed on admission to surgical intensive care unit (SICU). Risk factors for AKI were ruptured AAA (odds ratio (OR) = 5.846, 95% confidence interval (CI): 1.346 - 25.390), intraoperative hypotension (OR = 6.008, 95%CI: 1.176 to 30.683), and perioperative blood transfusion (OR = 4.611, 95%CI: 1.307 - 16.276). Goal-directed hemodynamic optimization resulted in 75.0% complete and 18.8% partial renal recovery. Overall in-hospital mortality was 2.8%. AKI was associated with significantly increased length of stay ((136.9 ± 24.5) hours vs. (70.4 ± 11.3) hours) in Surgical Intensive Care Unit.

CONCLUSIONSCritically ill patients undergoing AAA repair have a high incidence of AKI, which can be early recognized by RIFLE criteria. Rupture, hypotension, and blood transfusion are the significant associated risk factors. Application of goal-directed hemodynamic optimization in this cohort appeared to be effective in improving renal outcome.

Acute Kidney Injury ; diagnosis ; etiology ; Aged ; Aortic Aneurysm, Abdominal ; surgery ; Critical Illness ; Endovascular Procedures ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Retrospective Studies ; Risk Factors

This study was purposed to compare the immunophenotypic and clinical characteristics of NPM1 mutated acute myeloid leukemia with a normal karyotype under the similar constituent ratio of FAB subtypes. Immunophenotyping and NPM1 gene mutation type-A,B and D and other leukemic related fusion genes were detected by multiparameter flow cytometry and real time RT-PCR or PCR, respectively. 77 AML patients with a normal karyotype (NK) and mutated NPM1 gene (NPM1m(+)AML) detected by immunophenotyping assay were included in this study. 55 cases without NPM1 mutation (NPM1m(-)AML) and with normal karyotype were served as negative control. The results showed that there was significant difference between NPM1m(+)AML and NPM1m(-)AML in terms of sex, white blood count, platelet counts, blast, WT1 expression level, FLT3-ITD mutation positive rate and response to treatment. The characteristic immunophenotype is lower expression of early differentiation-associated antigens (CD34, HLA-DR, CD117, CD38), lymphocytic antigens (CD7, CD4, CD19, CD2) and higher expression of CD33 and CD123 (P < 0.05). When above features was further analyzed between the M1/2 and M4/5 subgroups in NPM1m(+)AML patients, the M1/2 cases retained a higher frequency in women and a higher WT1 expression level (P < 0.05) . Monocytic differentiation-associated antigens including HLA-DR and lymphocytic antigens CD7 were higher expressed and CD117 was lower expressed in M4/5 subgroup (P < 0.05). It is concluded that under condition of similar constituent ratio of M1/2 and M4/5 subtype and normal karyotype, NPM1m(+)AML patients have higher WT1 expression level and better response to treatment. The major immunophenotype features of NPM1m(+)AML patients are lower expression of early differentiation antigens and lymphoid lineage antigens and higher expression of CD33 and CD123. Monocytic differentiation-associated antigens only higher are expressed in M4/5 cases when compared with M1/2 cases within NPM1m(+) AML patients.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Humans ; Immunophenotyping ; Karyotype ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; immunology ; Male ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; Young Adult