Sorafenib is a novel oral multikinase inhibitor that inhibits Raf kinase because of its anti-proliferative property. Sorafenib also inhibits receptor tyrosine kinases of multiple proangiogenic factors, such as VEGFR-1/2/3 and PDGFR-β. The combina-tion of both its anti-proliferative and anti-angiogenic properties makes sorafenib an attractive agent in cancer treatment. To date, sorafenib is the only approved systemic treatment for patients with hepatocellular carcinoma. The most common adverse events of this inhibitor included hand-foot skin reactions, nausea, diarrhea, weight loss, and hypertension. These adverse events can severely affect patient compliance, which may negate the effect of therapy. Correct understanding and treatment of these adverse events can improve clinical outcome. This paper discusses the clinical aspect of sorafenib-induced adverse events and the molecular basis behind their toxic-ity. Recommendations for the management of the adverse effects are also provided.

Gene Rearrangement, T-Lymphocyte ; Genes, T-Cell Receptor ; genetics ; Genotype ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Lymphoma, Non-Hodgkin ; genetics ; Polymerase Chain Reaction ; methods

BACKGROUND: It is proved that protein of heat shock protein 70 family has protective effects on cells. Ketamine can cause psychiatric symptoms such as illusion and delirium in patients, which can damage neurons of the limbic system in rats. The expression of heat shock protein 70 can be detected in the damaged neurons with immunohistochemical staining.OBJECTIVE: To observe the expression of heat shock protein 70 induced by ketamine in the hippocampus of rats of different ages and probe into the damaging effect on nerves.DESIGN: Randomized controlled trial.SETTING: Department of Anesthesiology and Critical Care Medicine,Huaxi Hospital of Sichuan University.MATERIALS: The experiment was conducted in the laboratory of the Department of Anesthesiology and Critical Care Medicine, Huaxi Hospital of Sichuan University, from January to May 2001. Totally 70 SD rats,weighing 25 to 285 g, of either gender and clean grade, were recruited.Thirty-five adult SD rats were randomly divided into control group and ketamine groups of 20.0, 40.0, 60.0, 80.0, 100.0 and 120.0 mg/kg with 5 rats in each group. The rats in each group were injected intraperitoneally with normal saline and 20.0, 40.0, 60.0, 80.0, 100.0 and 120.0 mg/kg of ketamine, respectively. Another 35 rats aged 0-10, 11-20, 21-30, 31-45,46-60, 61-90 and 91-120 days, 5 rats in each age stage, were given intraperitoneal injection of 80.0 mg/kg ketamine. After 24-hour survival time, the animals were put to death and their brains were removed. 5 μm-thick coronal sections of the hippocampus were cut on a vibratome. The expression of heat shock protein 70 was detected in the hippocampus of rats of different ages with immunohistochemical staining.MAIN OUTCOME MEASURES: Positive cellular percentage, density and grayscale of heat shock protein 70 in the rats' hippocampus.of different doses of ketamine on the expression of heat shock protein in rat hippocampus: In control group, the cellular density of heat shock protein 70 expression induced by 20.0, 40.0, 60.0, 80.0, 100.0 and 120.0 mg/kg of ketaminewas0, 8.12±1.82, 27.07±5.98, 45.35±5.84, 78.51±7.34,74.16±8.17 and 60.84±6.27, respectively. It indicated that when ketamine was under 80.0 mg/kg, the cellular density of heat shock protein 70 in creased significantly with the dose increase (P ＜ 0.01). When ketamine was over 80.0 mg/kg, the cellular density significantly decreased with the dose tamine in the hippocampus of rats of different ages: The density of positive nerve cells of heat shock protein 70 in young rats aged under 20 days was 0; the density of young rats aged 21-30 days, 31-45 days, 46-60 days and 61-90 days was 34.17±6.18, 55.42±4.80, 78.51±7.34 and 83.16±11.10,respectively. Compared with that of the first age group, with the increased age, the density of positive cells of heat shock protein 70 was significantly increased (P ＜ 0.01); it was 83.16±11.10 and 85.83±9.33 in the hippocampus of rats aged 61-90 days and 91-120 days, re spectively (P ＞ 0.05).CONCLUSION: Ketamine can induce the expression of heat shock protein 70 in the hippocampus of rats, indicating that neurons of the hippocampus may be damaged; with the increase of dose, its damaging effect is enhanced.The damage of ketamine is greater in adult rats than in young rats.

BACKGROUND:Stem cel transplantation has incomparable superiorities in the treatment of cardiovascular diseases. But stem cel s have a very low efficiency to differentiate into myocardial cel s spontaneously, and there are many factors influencing stem cel differentiation. OBJECTIVE:To clarify the pros and cons of different sources of stem cel s in the treatment of myocardial infarction, to investigate the methods for improving the differentiation efficiency of myocardial cel s, optimal differentiation conditions and mechanism underlying exercise-induced stem cel mobilization and endogenous myocardial cel regeneration. METHODS:A computer-based search of CNKI and PubMed databases was performed by the first author for articles related to stem cel therapy for myocardial infarction and stem cel differentiation into myocardial cel s, exercise effect on stem cel proliferation and myocardial cel regeneration published from 1985 to 2015. The key words were“stem cel s, myocardial infarction, myocardial regeneration, cardiac cel , exercise”in Chinese and English, respectively. Final y, 54 articles were included in result analysis. RESULTS AND CONCLUSION:In recent years, a variety of chemical inducers and biological components have been used in the myocardial differentiation of stem cel s. Simulation of myocardial microenvironment and vascular cel growth factors are the main methods of inducing myocardial differentiation. Aerobic exercise-induced stem cel mobilization can induce ischemic cardiac angiogenesis and upregulate a variety of vascular endothelial growth factors so as to promote myocardial proliferation and repair. However, in-depth exploration is stil needed in the harvesting of stem cel s, transplant rejection, and regulatory mechanisms underlying the directed differentiation of stem cel s into cardiomyocytes.

Objective To study the direct oblique images of normal temporal bones such as facial nerve canal, ossical chain, otic capsule and other structures. Methods 63 normal temporal bones were examined on direct oblique CT. The images were compared with cadaveric bone. Results The direct oblique images clearly showed the external auditory meatus, epitympanum, mastoid antrum, ossical chain, mastoid facial canal, otic capsule, internal auditory canal in 63(100%) temporal bones, the tympanic facial canal in 42(66 7%), the anteriorgenu in 55(87 3%), and the vestibular aqueduct in 58(92 1%). Conclusion Besides axial and coronal CT, direct oblique CT scan is also an important imaging method, which may provide valuable evidence for diagnosis and operation about ear diseases.

OBJECTIVE:To promote essential drug list into practice.METHODS:Relevant problems on the selection of National Essential Drug List were explored and analyzed.RESULTS & CONCLUSION:There are some problems on coordination of safety and effectiveness of drugs,price and the selection of traditional Chinese medicine.The advantage of first choice of essential drugs is not reflected completely.Large or small problems exist in selection process and individual drug verification.There was low credibility of drug evaluation.On the whole,the selection and formulation of essential drug list should be adjusted and improved continuously to guarantee the requirement of public medication.

OBJECTIVE:To analyze the problems of TCM injection included in Primary Medical Institutions Parts of National Essential Drugs List(2009 edition).METHODS:Danshen injection was taken as an example.The chemical composition of it (including water-soluble ingredients,fat-soluble components,other types of compounds,inorganic elements,proteins,tannins,polysaccharides,volatile oil),adverse reactions and quality standards were analyzed to investigate the problems of TCM injection included in Primary Medical Institutions Parts of National Essential Drugs List(2009 edition).RESULTS & CONCLUSION:Complex chemical composition of TCM injection and poor controlled quality standards require the further study.Because the safety of TCM injection is difficult to be guaranteed,it is necessary that reevaluation,research,consolidation of TCM injection.

Objective To study whether G3PD modifier protein (MP) could repair tubular epidermal cell(TEC) and ameliorate renal functions in aged rats with gentamycin induced acute tubular necrosis(ATN). Methods Aged and young rats were randomly divided into 3 groups, namely aged and young normal groups, aged and young model groups and the aged and young MP groups. The animal models of acute renal failure (ARF) were induced by gentamycin (140 mg?kg -1 ?d -1 , ip?7 d). Nitric oxide (NO) concentration was determined by Cd activated cadmium reduction method, malonaldehyde(MDA) with thiobarbituric acid test, superoxide dismutase(SOD) with hydroxylamine test, serum creatinine (Scr) with picric acid method, and the renal histology was observed by light and electron microscopy. Results NO was significantly higher in the aged MP group than that in the aged model group 〔serum: (94.29?7.68)?mol/L vs (70.14?5.53)?mol/L, P

The safety and effectiveness of catheter ablation in coronary sinus using radiofre-quency energy was studied in 16 dogs. Radiofrequency energy(1229?711 J) was applied between electrode catheter placed inside coronary sinus and a chest wall patch. Thirteen dogs were killed approximately half an hour after ablation and three 3 to 4 weeks. Lesion of abltion area were 3. 2?1. 8mm in length, 2. 2?1. 7mm in width and 2. 1?1. 0mm in depth. Microscopic examination showed well circumscribed area of coagultion necrosis (acute period)and fibrosis (chronic period). The coronary atery and mitral apparatus were not involved,nor was the endocadium. No arrhyth-mias except occationally atrial or ventricular premature beats were observed. No hemodynamic changes and rupture of coronary sinus occurred in any dog. Large amount of radiofrequency energy can be safely applied to the coronary sinus. The location of the lesions produced suggests that this technique may be useful for interruption of left-sided atioventricular pathways of patients.

Objective To evaluate the efficacy and safety of TUEVP vs TURP for treating benign prostatic hyperplasia(BPH).MethodsLiferatures on randomized controlled trials(RCT),non-randomized controlled trials(NRCT) and retrospective controlled trials of both Chinese and English studies about TUEVP vs TURP for the treatment of BPH all over the world were searched by Pubmed,Ovid,ScineceDirect,NGC,EBSCO,EMBASE,CNKI,CBM,as well as manual search of four Chinese journals: Chinese of Journal of Androloy,National Journal of Androlgy,Chinese Journal of Urology,Journal of Clinical Urology.Two reviewers independently screened the studies for eligibility,evaluated the quality and extracted the data from the eligible studies,with confirmation by cross-checking.Divergences of opinion were settled by discussion or consulted by the expert.Meta-analysis was processed by Rev Man 5.0,fail-safe number(Nfs) was performed by SAS8.0.ResultsSeventeen RCTs involving 2413 men were enrolled the inclusion criteria in Meta analysis.The baseline of patients' characteristics was comparable in all the studies.By evaluating the relevant indicators,side effects and complications between TUEVP and TURP,the statistically significant differences of pooled estimates suggested a benefit of TUEVP over TURP for bladder wash-out time,catheterization time,hospital stay,incidence of ED(20.6% vs 29.0%).In contrast,pooled estimates of the difference favoured TURP over TUEVP for MFR and incidence of postoperative secondary hemorrhage(7.9% vs 3.6%).ConclusionThis formal meta-analysis suggests that both TUEVP and TURP in patients with BPH provide comparable improvements,whose efficacy and safety is similar.While comparative analysis is limited by the methodological shortcomings of the underlying studies and the short follow-up,both TURP and TUEVP may offer distinct advantages.More high quality trials with large sample and longer follow-up are proposed,which will provide more evidence about evidence based medicine.