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.

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.

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 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.

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

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

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

OBJECTIVEThe aim of this study was to investigate whether miR-449a, miR-449b and miR-192 family microRNAs play the same roles in p53 pathway as miR-34 family in ovarian cancer.

METHODSWild-type p53 ovarian carcinoma cell line A2780 cells were treated with genotoxic agent adriamycin. The reactivation of p53 was detected by Western blot. The expression of miR-449a/b, miR-34a, miR-34b, miR-34c, miR-192 and miR-194 were detected by real-time quantitative PCR. Mutant p53 ovarian cancer cell line SKOV3.ipl cells were transfected with pre-microRNAs and the cell-cycle changes were detected. The expression level of miR-449a/b, miR-34a, miR-34b, miR-34c, miR-192 and miR-194 in serous ovarian carcinomas of varying grade and stage were compared with real-time PCR.

RESULTSThe expressions of miR-449a/b, miR-34b and miR-34c were 19-fold to 21-fold elevated after p53 activation by genotoxic agent. Ectopic expression of miR-449b, as well as miR-34c, resulted in cell-cycle arrest in SKOV3.ipl cells. The expression of miR-449a/b was parallel with that of miR-34b, miR-34c, and were significantly lower in late stage and high-grade serous carcinomas than in the normal fallopian tube, early stage and low-grade serous carcinomas. The expression of miR-192, miR-194 and miR-34a did not show evident features in serous ovarian carcinomas and were much lower than miR-449a/b, miR-34b and miR-34c in normal fallopian tube.

CONCLUSIONSAs tumor-suppressor microRNAs, miR-449a/b, miR-34b and miR-34c cooperate and play important roles in p53 pathway. Their inactivation may contribute to the carcinogenesis and progression of serous ovarian carcinomas.

Adult ; Aged ; Antibiotics, Antineoplastic ; pharmacology ; Cell Cycle ; Cell Line, Tumor ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; pathology ; Doxorubicin ; pharmacology ; Female ; Humans ; MicroRNAs ; genetics ; metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Transfection ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo investigate clinical outcome of surgical treatment for spinal metastatic tumors.

METHODSThirty-six patients with metastatic spine tumors treated surgically were retrospectivly reviewed from September 2005 to August 2010. There were 15 males and 21 females with an average age of 58 years old (ranged, 27 to 79 years). The site of origin of primary cancer included the breast, prostate, colon, lung, liver, esophagus, kidney, carcinoma, bladder, and 10 patients were with unidentified primary cancer. Five lesions were located in the cervical spine, 17 in the thoracic spine, 13 in the lumbar spine and 1 in the sacral vertebrae. Preoperative evaluation was conducted according to Tokuhashi system: total score 0 to 8 in 9 cases, 9 to 11 in 25 cases, 12 to 15 in 2 cases. The surgical procedures, including PVP, tumor resection and decompression, titanium nets implant, artificial vertebra replacement, bone cement stuffiness and inter fixation, were performed based on Tokuhashi score, location of lesions and neurological symptoms.

RESULTSAll the patients were followed up, and the during ranged from 2 months to 60 months with a mean time of 10.8 months. Pain relief was obtained in all patients after operation, and the VAS pain scores declined after operation. Among 14 patients suffering from spinal cord and nerve compromise, 12 patients improved 1 to 2 grades after surgery according to the Frankel grading system. According to the system of the ECOG performance status: 28 patients improved 1 to 2 grades in performance status after surgery. The postoperative survival rates at 3 months, 6 months, 1 year and 2 years were 97.2%, 63.9%, 38.9% and 16.7% respectively. Six patines had bone cement leakage after PVP, and none resulted in severe complications.

CONCLUSIONAccording to single or multiple spinal metastases, neurological symptoms, spinal stability and patients' condition, the different surgical treatments can be selected for spinal metastatic patients, which can relieve pain, maintain or improve the neurological status, improve quality of life, improve survival rate of patients.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Retrospective Studies ; Spinal Neoplasms ; mortality ; pathology ; surgery ; Survival Rate