Biotinidase deficiency is an autosomal recessive genetic disease with the decrease of biotinidase activity,which is caused by mutations of biotinidase gene.In recent years,with the development of genetic metabolic disease screening,biotinidase deficiency has been diagnosed constantly.Its incidence is about 1 ∶ 60 000 persons overseas and its clinical manifestations are complicated with high mortality and morbidity.In this paper,advances on pathogenesis,clinical manifestations,diagnosis and treatment of biotinidase deficiency will be reviewed.

Conformal radiotherapy is an important therapeutic strategy for primary hepatic carcinoma,which has high local control rate.However,the frequency of intra- and extra-hepatic recurrences is very high.Sorafenib is the only drug that has been demonstrated effectiveness to increase overall survival in advanced or metastatic hepatocellular carcinoma.The combination about radiotherapy and sorafenib can increase the radiosensitiveness,and inhibit the angiogenesis,and relieve the hypoxia,as well as synchronize the cell cycle.A lot of biological studies of sorafenib combined with radiotherapy have been camied out,and the phase Ⅰ -Ⅱ clinical trials are is in progress.

A growing body of evidence has indicated the important role of autophagy receptors in directing ubiquitinated or non-ubiquitinated cargos towards autophagy. Autophagy receptors bind to LC3 (microtubule-associated protein 1 light chain 3) on phagophore and autophagosome membranes, and recognize signals on cargoes in the delivery system of autophagy. However, the diverse domains in the receptor structures determine that their roles would never be limited to autophagy. Up to date, increasing numbers of the receptor proteins have been demonstrated to serve as a molecular link or switch participating in autophagic degradation, apoptosis or cell survival signals. Here, we highlight the non-autophagic roles of these receptor proteins to draw attention to this growing research topic.

OBJECTIVE:To establish an HPLC method for content determination of isoniazid and isonicotinic acid in isoniazid tablets.METHODS:The determination was performed on SHIM-PACK VP-ODS C18 column.The mobile phase consisted of methanol-water(0.2% docusate sodium,40 :60) at a flow rate of 0.8 mL?min-1.The UV detection wavelength was set at 261 nm and the sample size was 5 ?L.RESULTS:The linear range was 10～1000 ?g?mL-1 for isoniazid(r=0.999 8) with average recovery of 99.57%(RSD=0.26%) and 2～24 ?g?mL-1 for isonicotinic acid(r=0.9994) with average recovery of 98.96%(RSD=0.96%).The limited quantities were 0.05 ?g?mL-1,0.16 ?g?mL-1,respectively.CONCLUSION:The established method is simple,rapid and accurate,and suitable for content determination of isoniazid tablets.

Objective: To discuss the feasibility of immune tolerance in rat small bowel trans-plantation induced by immature dendritic cells isolated from SD and Wistar rat. Methods: Dendritic cells isolated from liver or bone marrow of inbred strain Wistar and SD rat were cultured for five to nine days. A week before operation, the recipient rats were injected 2?106 inmature DCs from vena dorsalis penis and observed. The models of heterotopic small bowel transplantation (SBT: SD→ Wistar)were established. Acute immuno- rejection levels were evaluated by HE. Results: Varying degrees of rejection were observed in 3, 5, 7 days after operation. Conclusion: Immature DC can induce allogenic immunological tolerance of rat small bowel transplantation.

Osteosarcoma is the most common aggressive malignancy of bone.Recent studies have discovered that exosomes can mediate intercellular transfer of biologically active molecules such as RNAs, dsDNA, and miRNAs.The specific membrane struc-ture and contents of exosomes are widely engaged into the exchange of material and information among tumor cells, which play an im-portant role in regulating the tumor microenvironment of osteosarcoma, mediating the expression of Wnt/β-catenin, TGF-βsignaling and inducing tumor cell immune escape.Exosomes derived from osteosarcoma cells with antigen-presenting cells cause significant anti-tumor effect by activating the immune response.Research on exosomes has therefore opened up a new avenue for treatment of osteosar-coma.In this article we review the role of exosomes in pathogenesis of osteosarcoma and its potential application on diagnosis and treat-ment of osteosarcoma.

“Multi-component Chinese medicine” was derived from effective clinical prescriptions, which is similar to natural medicines, and its form is similar to the fixed-dose compounds. The adaptable indications mainly cast chronic, intractable, and complex diseases. Its research targets of pharmacology mostly are diseases, symptoms or pathological process. Vivo and vitro experiments can be used in its researches. Its dose-effect relationship mostly shows non-linear relationship, and three elements (dose, efficacy and syndrome) are involved. However, the comprehensive evaluation method is still in the exploratory stag. In the safety evaluation, there were few general pharmacological researches, and the basis of toxicity and the relationship between amount and toxicity need further study. In combined optimization aspect, including identification of components and component ratio optimization, many methods have been developed, but it still needs to be developed in theory and systemic integration. Pharmacological mechanism researches focus on the multi-component, multi-target, multi-pathway, and multi-pharmacodynamics aspects, combined with new ideas and new technologies, such as systems biology, network pharmacology, etc. But as multi-component medicine, it should also be studied about the correspondence and network relationships of component and target, with a purpose to explain the contribution of each component in overall mechanism.

Objective To observe and compare the functional outcomes of early rehabilitation of persons who received primary bilateral or unilateral total knee arthroplasty (TKA).Methods Sixty-eight subjects were divided into a unilateral TKA group (36 cases) and a bilateral TKA group (32cases).All received the same professional rehabilitation program during an average postoperative hospital stay of (15.00 ± 3.71 ) days.At discharge,a visual analogue scale (VAS) was used to rate pain.Active range of motion (AROM) of the involved knee,knee injury and an osteoarthritis outcome score (KOOS) were also assessed.The KOOS and knee society score (KSS) were evaluated at follow-up about 11 months later.Results There was no significant difference between the two groups in any assessment at discharge,nor in the KOOS and KSS-Ⅰ assessments at follow-up.The KOOS of both groups at follow-up had improved significantly compared with that at discharge.The KSS-Ⅱ results in the bilateral group were slightly better than those in the unilateral group at follow-up,and that difference was significant.Conclusions Bilateral TKA patients and unilateral TKA patients had the same clinical outcomes after early postoperative rehabilitation,but the functional outcomes of bilateral TKA patients were better than those of unilateral TKA patients a year later.

Objective To investigate the effect of Shenfu injectio on insulin resistance in rabbits undergoing cardiopulmonary bypass (CPB) . Methods Thirty New Zealand white rabbits of both sexes weighing 2.2-2.5 kg were randomly divided into 3 groups (n = 10 each): group I sham operation (group S); group Ⅰ CPB and group Ⅰ CPB + Shenfu injectio (group SFI). In group IE (group SFI) Shenfii injectio 10 ml/kg was injected intraperitoneally (IP) once a day for 2 days and at 30 min before anesthesia. In group Ⅱ and Ⅲ the duration between aortic cross-clamping and unclamping was 60 min. MAP was maintained at 50-60 mm Hg during CPB. The plasma glucose and insulin concentrations were measured immediately after induction of anesthesia (T_1), immediately after aortic cross-clamping (T_2) , and at 5, 35 and 75 min after aortic unclamping (T_3, T_4 , T_5) and insulin resistance index (HOMA-IR) was calculated. The expression of insulin receptor substrate-1 (IRS-1), phosphatidyl-inositol 3 kinase (PI3Kp85) and glucose transporters (CLUT4) in skeletal muscle was detected at 150 min of CPB by immuno-histochemistry. Results Compared with the baseline values at T_1 , plasma glucose and insulin concentrations and HOMA-IR were significantly increased at T_(2-5) in all 3 groups ( P < 0.05) . CPB significantly increased the plasma glucose and insulin concentrations and HOMA-IR at T_(2-5) in group Ⅱ and Ⅲ as compared with group S ( P < 0.05). The expression of PI3Kp85 and GLUT4 in muscle was significantly decreased in group Ⅱ and Ⅲ as compared with group S ( P < 0.05). Shenfu injectio significantly decreased plasma glucose concentration and HOMA-IR and increased plasma insulin concentration in group fD as compared with group Ⅱ . Shenfu injectio significantly attenuated the CPB-induced changes in IRS-1, PI3Kp85 and GLUT4 expression in muscle. Conclusion Shenfu injectio can ameliorate CPB-induced insulin resistance and the mechanism may be related to the up-regulation of the expression of insulin signal transduction molecules in skeletal muscle.

Ewing's sarcoma is a kind of bone and soft tissue tumor which is highly invasive and mainly occurres in children and adolescents.In recent years,combined chemotherapy,surgery and radiation therapy in treatment of Ewing's sarcoma,patients' prognosis and life quality have been significantly improved.However,over the past 20 years,the treatment of Ewing's sarcoma entered the platform period.The 5-year overall survival rate remained at 55％-75％.Multiple metastasis and recurrence are the main factors of poor prognosis and death.Chemotherapy,radiotherapy and molecular targeted therapy are still the main methods for the treatment of Ewing sarcoma.The side effects,drug resistance and the use of the combination regimen of antitumor drugs have been plaguing the clinical workers.In order to improve the efficacy of chemotherapy drugs and reduce the toxic side effects,Multi-disciplinary and multi-center clinical studies on Ewing's sarcoma patients who suffered from local control or recurrence have been launched by Domestic and European and American countries.As an important supplementary mean for the treatment of Ewing's sarcoma,patients often appear a series of complications after radiotherapy,including the risk of local damage or secondary tumors.Therefore,it is necessary to further clarify the indications of radiotherapy and the timing of preoperative and postoperative radiotherapy.The specific chromosome translocation and the expression of the fusion gene EWS/FLI 1 have been found in Ewing sarcoma.Nevertheless,the mechanisms that drive tumor relapse and metastasis remain unknown.Molecular targeted therapy can be used to inhibit tumorigenesis and progression by regulating the upstream or downstream target genes of EWS/ FLI1.In conclusion understanding of the current treatment status of Ewing's sarcoma,results of multi-center clinical trials and theory of genomics research will contribute to the design of new biological therapies so as to establish individualized treatment modalities.In this paper,we present a review on the progress of Ewing sarcoma chemotherapy,radiotherapy,molecular targeted therapy and immunotherapy.