As one of the major sources of infection, viruses could infect all organisms including bacteria, plants, animals, and humans. Infectious diseases caused by viruses pose a great threat and damage to human health and economic activities all over the world. Adaptor-associated protein kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and a specific key kinase regulating the phosphorylation of AP-2 protein μ2 subunit T156. In the past, AAK1 has been regarded as a feasible biological target for the treatment of nerve pain. Recently, scientists have found that inhibiting AAK1 can regulate endocytosis and inhibit virus invasion into cells. Therefore, AAK1 could be the potential target of anti-virus therapy. This paper reviews the research progress of small molecule AAK1 inhibitors in the field of antiviral, analyzes the future research directions and challenges, and provides new ideas for the development of antiviral drugs targeting AAK1.

Antigens, CD34 ; metabolism ; Carcinoma, Signet Ring Cell ; genetics ; metabolism ; pathology ; surgery ; Codon ; Diagnosis, Differential ; Exons ; Female ; Follow-Up Studies ; Gastrectomy ; methods ; Gastrointestinal Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Gastrointestinal Stromal Tumors ; genetics ; metabolism ; pathology ; surgery ; Humans ; Melanoma ; metabolism ; pathology ; Middle Aged ; Neurilemmoma ; metabolism ; pathology ; Point Mutation ; Proto-Oncogene Proteins c-kit ; metabolism ; Receptor, Platelet-Derived Growth Factor alpha ; genetics ; metabolism

ObjectiveTo investigate the injury mechanism,clinical characteristics and surgical treatments of Segond fracture combined with anterior cruciate ligament (ACL) injury.MethodsNine patients suffering from Segond fracture combined with ACL injury were treated between January 2008 and December 2010.All the patients revealed ACL and medial collateral ligament (MCL) breakage under arthroscopy.Furthermore,one patient was associated with lateral collateral ligament (LCL) breakage and medial meniscus injury,four with medial meniscus tear and two with lateral meniscus tear.All the patients underwent arthroscopic tendon allotransplantation,ACL reconstruction and MCL repair.Besides,synchronous LCL reconstruction was performed in one patient,meniscus suture in three and meniscus plasty in four.Six patients with large Segond fracture fragments were fixed with two hollow lag crews and three with relatively small fracture fragments fixed with one hollow lag crew.ResultsThe mean followup period was 12 months,which showed average postoperative Lysholm score of 59 points and satisfactory clinical outcome.ConclusionsSegond fracture is often combined with ACL injury and is predictive for ACL injury.In ACL reconstruction,large Segond fracture blocks should be reduced and fixed and the combined injuries also should be treated in the same period.

Objective To investigate the prognostic impact of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and CD34 on invasion and metastasis of gastric cancer.Methods CEACAM1 and CD34 expressions were detected by immunhistochemistry in 90 cases of gastric cancer and 30 cases of normal gastric mucosa.Then the relationship among CEACAM1, MVD marked by CD34 antibody and gastric cancer patients` clinical pathological features and prognosis were analyzed.Results The positive rates of CEACAM1 and CD34 protein in gastric cancer were significantly higher than those in normal gastric mucosa (P<0.05).The positive rate of CEACAM1 was closely related to histological differentiation, tumor invasion, nodal metastasis and TNM stage.MVD marked by CD34 was related with tumor size, histological differentiation, tumor invasion, nodal metastasis and TNM stage(P<0.05).Conclusions In gastric cancer, CEACAM1 and CD34 promote its invasion and metastasis, and they are potential indicators of predicting development and prognosis.

Objective To develop a liquid chromatography tandem mass spectrometry(LC-MS/MS) method for determination of s teicoplanin in human plasma.Methods The plasma samples were precipitated by methnaol,then the supernatant were separated on Eclipse Plus C1s column (2.1 mm × 100 mm,3.5 μm) and eluted with methnaol-10 mmol · L-1 ammonium acetate(85:15,v/v,containing 0.1％ formic acid),and the column temperature was 25 ℃.Detection of the analyte was achieved using positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode.The MS/MS ion transitions monitored were m/z 1880.1→m/z 1563.0,m/z→748.8 m/z 158.1 for teicoplaninand internal standard,respectively.The specificity,standard curve and lower limitation of quantitation,precision and recovery rate,stability and matrix effect were investigated.Results The linear regression equation was y =1.63 × 10-2x-2.95 × 10-3(r =0.9963).The linear range of teicoplanin was 0.10-20.00 μg · mL-1,with the lower limit of quantitation (LLOQ) of 0.10 μg · mL-1.The accuracy was 93.56％-105.12％.Intra-day and inter-dayrelative standard deviations were both below 15％.The absolute recovery in plasma was 80.32％-88.28％.The matrix effect was 91.78％-108.56％.Conclusion The established method is rapid,sensitive,accurate,specific and reliable,and it is suitable for the determination of teicoplanin in human plasma and pharmacokinetic study.

OBJECTIVETo assess the changes of neurobehavioral function in a neonatal mouse model of excitotoxic brain damage.

METHODSFifty-five 5-day-old ICR neonatal mice were randomly assigned to three groups: blank (no intravenous) control (n=20), saline control (n=20) and excitotoxic brain damage model (ibotenic acid treatment, n=15). Behavioral function was evaluated by the surface righting reflex test (postnatal days 6-10), the swimming test (postnatal days 8-12) and the Y-maze discrimination learning test (postnatal days 33-34).

RESULTSRighting time in the surface righting reflex test in the ibotenic acid treatment group on postnatal days 6-10 was more prolonged than that in the two control groups (p<0.05). Swimming test scores in the ibotenic acid treatment group were significantly lower than those in the two control groups (p<0.05). In the Y-maze discrimination learning test, the mice from the ibotenic acid treatment group performed significantly worse than two control groups, presenting with increased learning times (19.79+/-2.42 vs 16.29+/-2.48 or 16.30+/-2.37; p<0.05) and achieving a lower correct percentage (86.7% vs 96.5% or 95.0%) (p<0.05).

CONCLUSIONSThe developmental reflexes and learning and memory functions were impaired in neonatal mice following excitotoxic brain damage. Behavioral testing is useful in the evaluation of early developmental reflexes and long-term neurobehavioral outcome in neonatal mice with excitotoxic brain damage.

Animals ; Animals, Newborn ; Behavior, Animal ; drug effects ; Brain ; drug effects ; Excitatory Amino Acid Agonists ; toxicity ; Female ; Ibotenic Acid ; toxicity ; Male ; Maze Learning ; drug effects ; Mice ; Mice, Inbred ICR ; Swimming

Child ; Child, Preschool ; Diuretics ; therapeutic use ; Edema ; drug therapy ; Female ; Furosemide ; therapeutic use ; Humans ; Male ; Nephrotic Syndrome ; complications ; Sulfonamides ; therapeutic use

Hypoxic pulmonary hypertension (HPH) is characterized by hypoxic pulmonary vasoconstriction (H P V) and hypoxic pulmonary vascular remodeling(HPVR). Previous studies have shown that intracellular Ca

OBJECTIVETo establish a murine model of sensitization, and investigate the effect and mechanism of sensitization on allogeneic donor bone marrow cells (BMCs).

METHODSSensitized BALB/c mice were established by transfusions of allogeneic splenocytes. The donor reactive antibodies were detected by binding and complement-dependent cytotoxicity assays. After irradiation, 1 × 10(7) BMCs of C57BL/6 donor mice were injected into non-sensitized or sensitized BALB/c recipient mice. The distribution pattern of donor BMCs in peripheral blood, spleen and bone marrow of recipient mice were analyzed at different time points (2 h, 12 h and 48 h) post transplantation. Hematopoietic recovery post transplantation was assessed, and survival was monitored. Moreover, sera and splenocytes derived from non-sensitized or sensitized recipients were incubated with allogeneic BMCs in vitro, and the cytotoxic indexes were calculated in the immune experiments.

RESULTSThe binding and complement-dependent cytotoxicity assays showed that a high level of donor reactive antibodies was presented in sensitized sera. Compared with the non-sensitized recipients, the homing assay showed significantly decreased distributions of allogeneic donor BMCs in peripheral blood, spleen and femur of sensitized recipients. Non-sensitized recipients survived long term after irradiation, while all the sensitized recipients died within 12-15 days. Fourteen days post transplantation, the white blood cells and BMCs of non-sensitized recipients were (3240 ± 300) × 10(6)/L and (396 ± 27) × 10(6)/femur, respectively; while the white blood cells and BMCs of sensitized recipients were (320 ± 80) × 10(6)/L and (6 ± 2) × 10(6)/femur, respectively; the differences were statistically significant between this two groups (P < 0.05). Seven days post transplantation, the percentage of donor cells in bone marrow of non-sensitized and sensitized recipients was (48.07 ± 4.70)% and (0.77 ± 0.11)%, respectively, and the differences were statistically significant (P < 0.05). Furthermore, the white blood cells and BMCs following transplantation decreased along with time in sensitized recipients. The immune experiments of complement-dependent cytotoxicity reaction, cytotoxic T lymphocytes reaction and antibody-dependent cellular cytotoxicity showed the cytotoxic indexes were higher in sensitized group than the non-sensitized group.

CONCLUSIONA sensitized model was established by transfusions of allogeneic spleen cells. Allogeneic donor BMCs were rejected in sensitized recipients, and its mechanism might be through immune impairment pathways.

Animals ; Bone Marrow Cells ; Bone Marrow Transplantation ; Disease Models, Animal ; Graft Rejection ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Tissue Donors ; Transplantation, Homologous

B-Lymphocytes ; Child ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; immunology ; Precursor Cells, B-Lymphoid ; pathology