One of the most promising antimalarial drugs which are widely used throughout the world is the artemisinin (ARS)and its derivatives,e.g.,artemether,arteether,and artesunate.Their true potential lies in broader anti-disease applications.The mechanism of action of these compounds appears to involve the endoperoxide bridge to produce carbon-centred free radicals.Large clinical studies did not show serious side effects,however,there is a paucity of large-scale clinical trials suitable to detect rare but significant toxicity.Therefore,a final and definitive statement on the safety of artemisinins still cannot be made.In contrast,animal experiments at high doses shown considerable toxicity upon application of artemisinins.In the present review,the authors give a comprehensive overview on toxicity studies in cell culture and in animals (mice,rats,rabbits,dogs,and monkeys)as well as on toxicity reported in human clinical trials.The authors emphasize the current knowledge on neurotoxicity,embryotoxicity, genotoxicity,hemato-and immunotoxicity and cardiotoxicity.Rapid elimination of artemisinins after oral intake represents a relatively safe route of administration compared to delayed drug release after intra-muscular (im ) injection. There are drug-related differences, i.e., intramuscular application of artemether or arteether,but not to artesunate,which is safe and gives good profiles after im administra-tion in severe malaria.It might also be important in determining dose limitations for treatment of other diseases such as cancer.Questions about dosing regimens,safety of long-term use and possible inter-actions with existing therapies and toxicities that might be related to the treatment of tumors should be answered by appropriate clinical and preclinical studies.

Objective When bacterial cellulose (BC) is used as a scaffold material in tissue engineering,the nano-structure of BC may not provide enough space for animal cell growth and differentiation which would not achieve a perfect application in tissue engineering.In order to solve this problem,a novel green approach is developed in this research to produce bacterial nanocellulose materials with micropores ranging 50-800 μm.Methods Several ratios of hydrogen peroxide to sodium chlorite were used to react instantly to produce a large number of bubbles in BC hydrogels,which formed micropores with diameters ranging 50-800 μm.Optical microscopy and scanning electron microscope were used to evaluate microporous BC hydrogels and verify the existence of micropores.Results The size of pores could be regulated along with the changes in the amount of reactants used in the experiment.Fourier transform infrared spectroscopy verified that no cellulose was oxidized.Water content of the microporous BC hydrogels was similar to that of the original BC hydrogels.The Young's modulus of microporous BC hydrogels was 26.1 kPa,which was lower than that of the original BC hydrogels (69.9 kPa).Thiazoyl blue tetrazolium bromide (MTT) test displayed a higher viability on the microporous BC hydrogels compared to the growth on the unmodified BC substrates.Conclusions This study provides a convenient and promising way to prepare microporous materials,which may not be limited to only BC material,but could be used in other hydrogels.The proposed approach is suitable for extensive industrialization.

Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1％) cases,Ta in 20(18.9％) cases and carcinoma in situ in 6 (5.7％) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5％) patients experienced tumor recurrence and 2 (1.9％) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5％.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95％CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1％ (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 ％),9 cases (3.3 ％) with economic reasons and 11 cases (4.0％) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.