Unresectable or metastatic pancreatic cancer carries a poor prognosis,and systemic therapy with cytotoxic agents provides marginal benefit. Even the first-line chemotherapeutic agent, gemcitabine(GEM) has a modest survival benefit,and objective tumor response is rarely achieved. Combination of various cytotoxics did not produce a significant improvement either. For that reason,continuous search for better molecules targeted agents and/or combinations is inevitable. Erlotinib, an orally bioavailable small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase, is the first of these targeted which compounds to be approved for use in combination with gemcimbine for patients with advanced pancreatic cancer. GEM with other targeted agents,including monoclonal antibodies: cetuximab or bevacizumab,also has been extensively evaluated,with limited success to date. Future research should continue to unravel the mechanism of pancreatic carcinogenesis and to identify key relevant molecular targets for therapeutic intervention.

It is well appreciated that hepatocellular carcinoma (HCC) represents one of the most challenging malignancies of worldwide importance. HCC is a disease that requires multidisciplinary management. There has been no widely accepted standardard systemic therapy for this disease until recently. However, with the arrival of newly developed, molecularly targeted agents, there has been renewed interest in developing novel systemic therapy in HCC. For this review, the authors concisely summarized the current status of molecular targeted agents: muhikinase inhibitor, antiangiogenesis and anti-EGFR agents, which are under clinical development, focus on new agents with promise, particularly sorafenib, a drug that appear to be the new standard of care for advanced HCC.

This article reviews the role of bevacizumab (BV) and cetuximab (C225) in the treatment of the patients with advanced or metastatic colorectal cancer(CRC). The molecules targeting agents BV and C225 are being specifically blocking biological response of VEGF and EGFR. The clinical application of these agents for CRC is effective and well tolerated. Unlike traditional chemotherapy, it primarily inhibits tumor growth rather than regression. The combination of targeted agents (BV and C225) with cytotoxic agents holds the promise of enhanced chemotherapy benefits, prolonged survival and improved quality of life for patients with CRC

Metastatic renal cell carcinoma (RCC) is currently one of the treatment-resistant malignamcies. However, the elucidation of the molecular mechanisms underlying RCC development has led to the identification of promising targets for novel therapeutic agents. In Clinical studies, sunitinib and sorafenib have shown significant activity with manageable toxicity in the treatment of advanced or metastatic RCC. Both are oral agents which belong to a class of multitarget drugs called kinase inhibitor that inhibit the VEGF, platelet-derived growth factor(PDGF) and C-KIT receptor tyrosine kinase, which have been rapidly approved in the second-line and will soon be used as first-line therapy for RCC. Further studies with sunitinib or sorafenib as monotherapy and combination regimens in the treatment of RCC are warranted.

This article reviews the proteasomes inhibition is a novel approach to cancer therapy. Bortezomib (velcade) is the first proteasomes inhibitor, it was effective in this class to be approved for clinical use. Phase I clinical trials established an optimal dosing strategy and demonstrated a manageable toxicity profile. Two phase II trial, SUMMIT and CREST demonstrated the safety and efficacy of bortezomib for patients with relapsed and/or refractory myeloma. The phase III APEX trial comparing bortezomib with high-dose dexamethasone demonstrated that bortezomib had an improved response rate, duration of remission and overall survival advantage in the setting of relapsed disease. These findings have led investigators to study bortezomib combination with conventional chemotherapy and other novel agents. Results of ongoing trial with bortezomib in the first-line treatment of myeloma have been extremely encouraging. Further studies with bortezomib as monotherapy and combination regimens in the treatment of hematologic and solid malignancies are warranted.

AIM To investigate the effects of ethyl acetate extract from Huangqi Injection (HQIEACE) on leucopenia mice.METHODS An experimental mouse model of leucopenia was induced by cyclophosphamide.NMR based metabolomic profiling technique coupled with multivariate statistical method was used for performing metabolomic analysis.RESULTS HQIEACE could elevate the levels of white blood cell,monocytes,neutrophils and lymphocyte in modeled mice.The levels of ten potential endogenous metabolites (lipid,leucine,3-D-hydroxybutyrate,lactate,alanine,pyruvate,creatine,scyllo-inositol,betaine and glucose) were reversed.CONCLUSION The metabolic pathways related to the pharmacological effects of HQIEACE on leucopenia are probably involved in body energy metabolism,amino acid metabolism,oxidative stress and choline metabolism.

Objective To explore the change of serum osteopontin concentration and the expression of OPN in the synovial membrane of patients with rheumatoid arthritis.Methods We measured the serum osteo-pontin concentration in 91 RA patients and 29 sex-and age-matched normal control subjects using an en-zyme-linked immunoabsorbent assay and collected clinic data at the same time.The expression of OPN in the synovial membrane from 7 RA patients and 1 patient with trauma was examined by immunohistochemisty.Results Serum osteopontin concentrations were significantly higher in both active and inactive RA patients than that in the normal control group:(65±22)ng/ml in active RA,(56±22)ng/ml in inactive RA patients and(26±8)ng/ml(P＜0.005)in normal controls.Increase in OPN concentration correlated positively and sig-nificantly with the number of tender joints,joint x-ray change stages,and joint function(r=O.435,P=0.005.r=0.415,P=0.007,r=O.394,PP=0.012).The expression of OPN was observed in all samples from patients.OPN was expressed in the synovial lining and sublining layer.Conclusion The above results suggest that the pro-duction of osteopontin is associated with joint destruction in RA.

In vitro compartmentalization (IVC) links genotype and phenotype by compartmentalizing individual genes (including expression system) or cells into a micro-droplet reaction region. Combined with fluorescence-activated cell sorting (FACS), it can detect and separate single droplets in ultra-high throughput. IVC-FACS screening method has been widely used in protein engineering, enzyme directed evolution, etc. However, it is difficult to control the homogeneity of droplet size by mechanical dispersion method in previous studies, which seriously affects the quantitative detection of droplets and reduces the efficiency and accuracy of this screening method. With the rapid development of microfluidic chip manufacturing technology, the microfluidic chip-based methods for droplet generation are becoming more efficient and controllable. In this study, firstly, the water-in-oil (W/O) single-layer droplet generation chip was used to prepare single-layer monodisperse W1/O droplets at a high generation frequency, and then the W1/O droplets were reinjected into water-in-oil-in-water (W/O/W) double-layer droplet generation chip to prepare uniform W1/O/W2 double-layer emulsion droplets. By optimizing the flow rate and ratio of the oil and water phases, a single-layer micro-droplet can be generated with a diameter range from 15.4 to 23.2 μm and remain stable for several days under normal incubation. Then the single-layer droplets were reinjected into the double emulsion generation chip. By adjusting the flow rate of drop phase, oil phase and water phase, the double-layer emulsion droplets with a diameter range from 30 to 100 μm at a rate of 1 000 droplets/s could be obtained. Escherichia coli embedded in the double-layer emulsion droplets could be cultured and induced for protein expression. This study lays a foundation for the establishment of a high-throughput screening method based on the droplet and flow cytometry.
Emulsions ; Flow Cytometry ; High-Throughput Screening Assays ; Microfluidics ; methods

OBJECTIVETo investigate the basic factors of the progress amplitude of hearing and speech rehabilitation effect of preschool deaf children with cochlear implants, and provide guidance for the improvement and optimization of rehabilitation strategies.

METHODUsing the standard hearing and language assessment tools, tracked and evaluated 1 422 CI preschool deaf children for a period of one year, and calculated the effect of hearing and speech rehabilitation, carried out the correlation analysis and variance analysis among different grouping variables.

RESULT(1) There was a negative correlation (P<0.01) between the rehabilitation effect and cochlear implantation age, existed the different degree of positive correlation (P<0.01) between the rehabilitation effect and parents cultural level, but no correlation between the rehabilitation effect and parents hearing status.(2) Father's education level, in comparison to mother's education level, had greater impact on the children rehabilitation effect.(3)There was positive correlation(r=0.689, P<0.01) between the progress amplitude of hearing and speech rehabilitation effect. (4) The progress amplitude of auditory and language rehabilitation effect of 2-3 years old group was the highest value(the progress amplitude of hearing and speech recognition rate reached 77.5%, the progress amplitude of language age progress rate reached 2.02 years old), and there were significant differences (P<0.05) between over 3 years old groups.

CONCLUSIONS(1) To expect the better progress amplitude of rehabilitation effect, cochlear implant age should not be more than 3 years old. (2) Father's effect in the process of rehabilitation is more helpful for deaf children's learning enthusiasms.

Age Factors ; Child, Preschool ; Cochlear Implantation ; Cochlear Implants ; Deafness ; rehabilitation ; Hearing ; Hearing Tests ; Humans ; Language ; Speech Perception

p-coumaric acid is an important natural phenolic compound with a variety of pharmacological activities, and also a precursor for the biosynthesis of many natural compounds. It is widely used in foods, cosmetics and medicines. Compared with the chemical synthesis and plant extraction, microbial production of p-coumaric acid has many advantages, such as energy saving and emission reduction. However, the yield of p-coumaric acid by microbial synthesis is too low to meet the requirements of large-scale industrial production. Here, to further improve p-coumaric acid production, the directed evolution of tyrosine ammonia lyase (TAL) encoded by Rhodotorula glutinis tal gene was conducted, and a high-throughput screening method was established to screen the mutant library for improve the property of TAL. A mutant with a doubled TAL catalytic activity was screened from about 10,000 colonies of the mutant library. There were three mutational amino acid sites in this TAL, namely S9Y, A11N, and E518A. It was further verified by a single point saturation mutation. When S9 was mutated to Y, I or N, or A11 was mutated to N, T or Y, the catalytic activity of TAL increased by more than 1-fold. Through combinatorial mutation of three types of mutations at the S9 and A11, the TAL catalytic activity of S9Y/A11N or S9N/A11Y mutants were significantly higher than that of other mutants. Then, the plasmid containing S9N/A11Y mutant was transformed into CP032, a tyrosine-producing E. coli strain. The engineered strain produced 394.2 mg/L p-coumaric acid, which is 2.2-fold higher than that of the control strain, via shake flask fermentation at 48 h. This work provides a new insight for the biosynthesis study of p-coumaric acid.
Ammonia-Lyases/genetics* ; Escherichia coli/genetics* ; Propionates ; Rhodotorula ; Tyrosine/genetics*