Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

As one of the most important components of caveolae, caveolin-1 is involved in caveolae-mediated endocytosis and transcytosis pathways, and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction. In recent years, the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored. In addition, the interplay between caveolin-1 and nano-drugs is bidirectional. Caveolin-1 could determine the intracellular biofate of specific nano-drugs, preventing from lysosomal degradation, and facilitate them penetrate into deeper site of tumors by transcytosis; while some nanocarriers could also affect caveolin-1 levels in tumor cells, thereby changing certain biophysical function of cells. This article reviews the role of caveolin-1 in tumor prognosis, chemotherapeutic drug resistance, antibody drug sensitivity, and nano-drug delivery, providing a reference for the further application of caveolin-1 in nano-drug delivery systems.

Objective BAG3-related myopathy is a rare condition so far reported in twenty patients worldwide.The purpose of this study was to draw attention to this rare disease and to the fact that BAG3-related myopathy should be considered as a rare differential diagnosis of hypercapnia.Methods We report a sporadic case of a 14-year-old Chinese girl with a de novo p.Pro209Leu mutation in BAG3 and reviewed the literatures for reported cases related to this mutation.Results We described a 14-year-old Chinese girl who presented with gradually appearing symptoms of hypercapnia that required assisted ventilation.The muscle biopsy and the blood whole-exome sequencing results confirmed the diagnosis of myofibrillar myopathy with a de novo p.Pro209Leu mutation in BAG3.Totally twenty-one patients from twenty families with a confirmed diagnosis of BAG3-related myopathy were reported to date,including this patient and literature review.The male to female ratio was 11 :10 and most showed initial symptoms in the first decade of life.Most patients presented toe/clumsy walking or running as the onset symptom,followed by muscle weakness or atrophy.Creatine kinase levels were elevated in fourteen patients and were normal in three.Eighteen patients developed respiratory insufficiency during the disease course and thirteen (one could not tolerate non-invasive assisted ventilation) required non-invasive assisted ventilation for treatment.Except for one not reported,heart involvement was found in seventeen patients during the disease course and seven underwent heart transplantation.Z-disk streaming and aggregation could be observed in most of the patients' muscle histology.In the long-term follow-up,five patients died of cardiac or respiratory failure.Conclusion BAG3-associated myopathy is a rare type of myofibrillar myopathy.It should be considered as a rare differential diagnosis of hypercapnia.

The dynamic or flowing tumor cells just as leukemia cells and circulating tumor cells face a microenvironment difference from the solid tumors, and the related targeting nanomedicines are rarely reported. The existence of fluidic shear stress in blood circulation seems not favorable for the binding of ligand modified nanodrugs with their target receptor. Namely, the binding feature is very essential in this case. Herein, we utilized HSPC, PEG-DSPE, cholesterol and two

Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin-biotin interaction with the help of c(RGDfK), magnetic fields and lasers. The ultrasmall superparamagnetic iron oxide nanoparticles (USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin (Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting.

In order to delete the immune tolerance of self-protein HER2 and produce an efficient immune response,the genetic code expansion technique was employed to introduce the immunogenic amino acid p-nitro-phenylalanine into the position 5 ,26 and 79 of the HER2 fragment and HER2 mutants containing p-nitropheny-lalanine were obtained.Prototype and mutant HER2 molecules with a purity of more than 95% were obtained through a nickel affinity column.Immunogenicity analysis of the HER2 vaccine showed that pNO2Phe79HER2 was able to produce high titer cross-reactive antibodies in C57BL/6 mice and that the mouse antisera could recognize SKBR-3 cells with intact HER2 receptor extracellular domain and cleave HER2 highly expressed HER2 +B16F10 cells through ADCC effect.These findings suggested that pNO2Phe79HER2 which incorporates p-nitro-phenylalanine could be used as a tumor vaccine candidate targeting HER2.

OBJECTIVE: To investigate the inhibition effect of total alkaloid, total phenolic acid and total volatile oil from Ligusticum chuanxiong on the contraction of the isolated uterine smooth muscle of rats, and to provide reference for clarifying the promoting blood circulation to restore menstrual flow traditional efficacy of L.chuanxiong. METHODS: The isolated uterine smooth muscle of rats were collected and soaked in Locke's solution. Using dimethyl sulfoxide as blank control, verapamil hydrochloride as positive control, the contraction curves of the isolated uterine smooth muscle in rats were recorded with PowerLab electrophysiolograph. Inhibitory effects of total alkaloid, total phenolic acid (mass concentrations of 0. 025, 0. 05, 0. 1 mg/mL) and total volatile oil (0. 04, 0. 08, 0. 16 mg/mL) on the contraction of the isolated uterine smooth muscle of rats induced by oxytocin were evaluated by observing the changes of contraction activity and contraction tension. Inhibitory rates of contraction activity and contraction tension of uterine smooth muscle were calculated. RESULTS: The contraction activity and contraction tension of uterine smooth muscle in rats were increased significantly after treated with oxytocin (P<0. 05 or P<0. 01). Different concentrations of 3 types of compounds from L. chuanxiong all decreased contraction activity and contraction tension of uterine smooth muscle significantly (P<0. 05 or P<0. 01). Compared with blank control, except for 0. 025 mg/mL total phenolic acid, the inhibitory rates of contraction activity and contraction tension of uterine smooth muscle were all decreased significantly (P<0. 05 or P<0. 01)after treated with other concentration drugs or components. CONCLUSIONS: The total alkaloid, total phenolic acid and total volatile oil from L. chuanxiong show certain inhibitory effect on the contraction of isolated uterine smooth muscle in rats, which provide reference for promoting blood circulation to restore menstrual flow use of L. chuanxiong.

In order to verify whether p-nitrophenylalanine-containing BAFF vaccine can be used as a candidate molecule for the treatment of autoimmune diseases with BAFF over-expression,a soluble mutant of B cell activating factor belonging to the TNF Family (smBAFF) and its pNO2Phe mutant(pNO2Phe65smBAFF),which site specific incorporated pNO2Phe at position 65 of smBAFF,were expressed and purified.In order to evaluate the feasibility of using pNO2Phe65 smBAFF to treat BAFF-over-expressed autoimmune diseases,we investigate its Lymphocyte-stimulating capacity,immunogenicity and inhibitory effect of serum on biological activity of natural BAFF.The pharmacological activity of pNO2Phe65 smBAFF was evaluated using a cGVHD(graft-versus-host disease) induced SLE mouse model.Results indicated that pNO2Phe65 smBAFF,could bind to mouse lymphocytes but could not promote the proliferation of mouse lymphocytes.Moreover,the incorporation of pNO2Phe significantly increased the immunogenicity and induced cross-antibody,which can inhibit the biological activity of natural BAFF.In cGVHD induced SLE mouse model,pNO2Phe65 smBAFF can significantly reduce the symptoms of the disease and play a therapeutic role.Therefore,pNO2Phe65 smBAFF can be used as a candidate molecule for the treatment of autoimmune diseases with BAFF over-expression.

Objective To explore impact of BMI on the clinical efficacy of treatment of type 2 diabetes mellitus after the laparoscopic gastric bypass. Methods Twenty patients were randomly selected from type 2 diabetes mellitus patients with BMI of 25 ~28 kg/m2 after laparoscopic gastric bypass surgery in our hospital from 2010 to 2013,20 patients from type 2 diabetes mellitus patients with BMI of 28~35 kg/m2 and 20 patients from type 2 diabetes mellitus patients with BMI≥35 kg/m2 . Accordingly,the total of 60 patients were divided into low BMI group,middle BMI group and high BMI group. The difference of the rate of blood glucose control and other indicators between three groups were compared and analyzed. Results The rate of blood glucose control in low BMI group was 75%,middle BMI group was 85%, and high BMI group was 90%. There was no statistical difference of the rate of blood glucose control between three groups at 12 months after laparoscopic gastric bypass surgery. The blood glucose and weight obviously improved in all patients,and fasting insulin and postprandial ser-um insulin decreased at 12 months after laparoscopic gastric bypass surgery. Conclusion All the patient of type 2 diabetes mellitus with dif-ferent BMI in three group can acquire satisfying clinical therapeutic effect after the laparoscopic gastric bypass.

Objective To discuss effect of synchronous families cognitive intervention on mental, behavioral characteris-tics in cervical cancer. Methods Selected 60 cases with cervical cancer were divided randomly into three groups, each of 20 cases. Group 1 was nursed by routine care, group 2 was nursed by cognitive intervention only for patients, and group 3 was nursed by cognitive intervention for patients and families. Anxiety, depression and behavioral characteris-tics of patients before and after intervention were surveyed by SAS, SDS and C type behaviors scale. Results After in-tervention, SAS and SDS of group 3 were lower than group 2, and group 2 was lower than group 1, which showed sig-nificant difference (P<0.05 or P<0.01). After intervention, anxiety dimensions, depression dimension of group 2 were lower than group 1, and group 3 were lower than group 2 (P<0.01); optimism dimensions, social support dimensions of group 2 were higher than group 1, and group 3 were higher than group 2 (P<0.01 or P<0.05). Conclusion Synchronous families cognitive intervention for patients with cervical cancer can improve anxiety, depression and behaviors.