Objective The paper reports anti-tumor activities and tumor radio-sensitivity research of the novel Estrogen compound 17a?-D-Homo Ethynylestradiol-3-Acetate to U_ 14 and S_ 180 sarcomas;and overall test high-activity and low toxicity traits of 17a?-D-Homo Ethynylestradiol-3-Acetate by the indexes of thymus gland,spleen,etc.Methods The mouse cervical cancer U_ 14 was selected and implanted in IRM-2 mice for anti-tumor assay,and sarcoma S_ 180 was selected for tumor radio-sensitivity assay,the drug was administered to all mice by i.v.way.Results 17a?-D-Homo Ethynylestradiol-3-Acetate has obvious anti-tumor activity to U_ 14 tumor,the best inhibitory rates is U_ 14 64.3%,and17a?-D-Homo Ethynylestradiol-3-Acetate has hardly any influence to hematogenous system(spleen index),immune system(thymus index);Nevertheless,the positive control drug CCP has obvious damage to spleen index and thymus index(P

Chalcone is a common scaffold in natural products with optimal properties and biological activities.In this study, we designed and prepared eight new coumarin-chalcone derivatives (5a-5h), and confirmed their structures by 1H NMR and 13C NMR. Their in vitro antifungal activity combined with fluconazole (FLC) against drug-resistant Candida albicans was tested by microdilution method.The results indicated that most chalcone derivatives showed good antifungal activity against drug resistant Candida albicans with FLC, particularly with compound 5g displaying better antifungal activity (MIC50 = 5.60 μg/mL) than FLC (MIC50 = 200 μg/mL) when combined with FLC, so, these derivatives could be used as synergists of antifungal drugs.

Objective To explore the impacts of Danhong injection on physiological and biochemical indicators in malnourished mice at physiological low doses, evaluate its safety, and test the practical value of safety re-evaluation of Traditional Chinese Medicinal ( TCM) injections. Methods A total of 32 ICR mice during growth period were selected to set up corn deficient nutrition mice model. Mice were assigned into the normal control group (given 0. 9% saline), Danhong injection at low, medium and high dosages (0. 2, 0. 4 and 0. 6 mL) groups (n=8 in each group);Mice were administered with respective medications intraperitoneally for 7 consecutive days. Blood samples were taken and mice were executed on the 8th day. All 9 kinds of organ or tissue were obtained completely, to measure related physiological and serum biochemical parameters. The safety of Danhong injection was evaluated by using Benefit and Damage Index - General Score ( BDI-GS ) system. Results The Danhong injection showed only slight damages on major organs or tissues, the BDI values were all above 0. 85, and the GS values were all above 9. 0;BDI values for Danhong injection at different dosages were all above 1. 0 for spleen and pancreas, showing better replenishing and healthy effects, and the differences were of statistical significance compared with the normal control group (P<0. 05 or P<0. 01). Meanwhile, it exerted obviously hypoglycemic effect. Conclusion Danhong injection is of rather low risk under physiological dosages, and therefore is safe to use. The mal-nutrition model combined with the BDI-GS system may be developed as a novel approach for safety re-evaluation of TCM injection in clinic.

Objective To study the protective effect of pyrrolidine dithiocarbamate (PDTC) on acute irradiated mice.Methods The 6-8 weeks old male ICR mice were randomly divided into five groups:irradiation alone group (IR),positive control group (amifostine WR-2721 250 mg/kg) and PDTC of 30,60 and 90 mg/kg dose groups.Each group had 10 mice and the drug was given at 0.5 h before whole body irradiation.At 30 d post-irradiation of 7.5 Gy 137 Cs γrays,the mice survival were observed.At 8 d post-irradiation of 5.0 Gy 137 Cs γ-rays,the peripheral blood,hematopoietic system and organ indexes were observed to evaluate the radiation protective effect of PDTC.Results PDTC increased the 30-day survival rates and 60 mg/kg dose had the most obvious effect by increase the survival to 60％ (6/10).The survivals of irradiation alone group and the amifostine positive control group was 10％ (1/10) and 70％ (7/10),respectively.Compared with the irradiation alone group,60 mg/kg PDTC group had the significant difference in spleen index,WBC,HGB,PLT,bone marrow nucleated cells and colony forming unit of spleen (t =2.354,4.793,2.342,6.542,2.649,3.982,P ＜ 0.05).Conclusions PDTC is effective in radiation protection with an optimum dose of 60 mg/kg.

Objective To conduct the comparative comprehensive evaluation on the actual healthy effects and safety of two kinds of healthy foods capsule A and B made of Chinese medicinal herbs on sale through the low-nutritional sub-health mice model com-bined with the benefit-damage index-general score(BDI-GS) approach ,and to perform the discussion on the relevant problems a-round healthy foods .Methods The experimental healthy ICR male mice during growth period were fed with maize low-nutritional feed and the mixed feed with 3 doses of 0 .25% ,0 .5% ,0 .75% healthy foods for 12 d and the mice body masses were recorded .Af-ter dissection ,9 items of the organ index and their BDI ,GS and serum biochemical indicators were performed the statistics .Results In the capsule A ,the medium and high dose groups manifested certain health-promoting effect ,while the slight negative effect exis-ted in the low dose group ,which was expressed in the GS values ;but in the capsule B ,3 doses all caused the damage to main internal organs in different degrees ,which was expressed in BDI<1 .0 and GS<9 .0 .Conclusion At present ,despite of possessing similar ingredients ,Chinese medicinal healthy foods in market are of greater differences in intrinsic qualities ,and even partial products have some adverse effect ,the healthy functions and safety are not enough to be fully ensured .Through the systematic evaluation of the BDI-GS system ,the criteria of marketing threshold for healthy foods will be increased so as to enhance their effects and safety level .

Objective To evaluate the tonic and health effects of Xuebijing injection,a traditional Chinese medicine injection,by means of corn low-nutritional mice model combined with benefit-damage index-general score (BDI-GS) evaluation system under a physiological dosage.Further,to investigate the scientific and practical benefits of the evaluation system in efficacy and safety re-evaluation of clinical traditional Chinese medicine injections.Methods Healthy ICR mice during growth period were randomly divided into blank control group and low,middle and high dose groups.All the mice were fed with corn diets,and treated by intraperitoneal injection once a day.The mice in the blank control group were injected with 0.4 ml 0.9％ sodium chloride injection,and the mice in the low,medium and high dose groups were injected with 0.2,0.4 and 0.6 ml Xuebijing injection,respectively,for seven days.On the 8th day,the mice were killed,dissected,and took nine kinds of organs including heart,lung,thymus,spleen,pancreas,kidney,gonad and femur.The weight BDI,index BDI and the corresponding weight BDI general score (GSw) and index BDI general score (GSI) were calculated,and the serum biochemical parameters were measured.Results Under the physiological dose,Xuebijing injection shows good safety of continuous infusion,tonic and health effects,and slight damages on the rest of organs.More specifically,the values of weight BDI and index BDI were all higher than 9.0,and values of GSw and GSI were all higher than the basic value of 9.0.Furthermore,these parameters increased in a dose-dependent manner.In addition,the total protein level of (47.6 ± 4.30) g/L in the high dose groups was significantly higher than (43.18 ± 2.60) g/L in the blank control group (P＜0.05).Conclusions The Xuebijing injection has a lower risk for conventional usage.This injection is safe under the physiological dosage and much safer in higher dosage designed in this study.The low-nutritional model combined with BDI-GS evaluation system can be used for re-evaluating the function and safety of clinical traditional Chinese medicine injections.

Objective:To evaluate the efficacy and safety of oral semaglutide versus sitagliptin in Chinese patients with type 2 diabetes mellitus(T2DM) inadequately controlled with metformin. Methods:The PIONEER 12 study was a phase Ⅲ clinical trial. Chinese patients were prospectively randomized to oral semaglutide(3mg, 7 mg, and 14 mg) or sitagliptin 100 mg. The primary endpoint was the change in HbA 1C from baseline to week 26, and the confirmatory secondary efficacy endpoint was the change in body weight from baseline to week 26. Results:Totally 1 084 Chinese participants(mean age 53 years, male 62.2%, mean duration of diabetes 5.5 years, HbA 1C 8.2%, and body weight 74.3 kg) were enrolled. The changes in HbA 1C at week 26 from baseline were -0.9%, -1.4%, and -1.6% for oral semaglutide 3 mg, 7 mg, and 14 mg, respectively, and -0.7% for sitagliptin. Compared to sitagliptin, oral semaglutide 3 mg, 7 mg, and 14 mg significantly reduced HbA 1C [estimated treatment difference(ETD), -0.2%(95% CI -0.4--0.0), -0.8%(95% CI -0.9--0.6), and -0.9%(95% CI -1.1--0.8), respectively; 3 mg, P=0.011, 7 mg and 14mg, P<0.001]. The estimated mean changes in body weight at week 26 from baseline were -1.1 kg, -2.5 kg, and -3.4 kg for oral semaglutide 3 mg, 7 mg, and 14 mg, respectively, and -0.4 kg for sitagliptin 100 mg. Compared with sitagliptin, oral semaglutide 3 mg, 7 mg, and 14 mg significantly reduced body weight [ETD, -0.8 kg(95% CI -1.3--0.2), -2.1 kg(95% CI -2.6--1.6), and -3.0 kg(95% CI -3.5--2.5), respectively; 3 mg, P=0.004, 7 mg and 14 mg, P<0.001]. The overall incidence of adverse events was similar across all treatment groups. The most common adverse events were gastrointestinal disorders, mostly mild or moderate in severity and transient in duration. Conclusions:Oral semaglutide resulted in significantly greater reduction in HbA 1C and body weight versus sitagliptin at week 26, with a favorable safety and tolerability profile in Chinese T2DM patients inadequately controlled with metformin.

Objective:To investigate the efficacy and safety of oral semaglutide in Chinese patients with type 2 diabetes mellitus(T2DM) inadequately controlled by diet and exercise only.Methods:In the randomized, double-blind, multicenter, multinational PIONEER-11 trial, Chinese patients were prospectively randomly assigned to receive oral semaglutide 3, 7, or 14 mg, or placebo. The primary endpoint was the change from baseline in glycated hemoglobin(HbA 1C) at week 26. This is a pre-defined subset analysis to assess the efficacy and safety in Chinese patients. Results:Totally 390 Chinese T2DM patients were enrolled(mean age 51 years), with a T2DM duration of 1.8 years, HbA 1C of 7.9%, and BMI of 26.5 kg/m 2 at baseline. Overall, changes at week 26 from baseline in HbA 1C were -1.1%, -1.6%, -1.6%, and 0.0%, and in bodyweight were -0.7, -1.9, -2.6, and -0.7 kg in oral semaglutide(3, 7, or 14 mg) and placebo groups, respectively. Compared to the placebo group, estimated treatment differences(ETDs) in HbA 1C for the 3, 7, and 14 mg groups were -1.2%(95% CI -1.4, -0.9), -1.7%(95% CI -1.9, -1.4), and -1.6%(95% CI -1.9, -1.4)(all P<0.001), respectively, and in weight loss for the 7 mg and 14 mg groups were -1.2 kg(95% CI -2.1, -0.4; P=0.006) and -1.9 kg(95% CI -2.8, -1.0; P<0.001), respectively. The most frequent gastrointestinal adverse events were diarrhea(oral semaglutide: 3.1%-12.5% vs placebo: 2.0%) and nausea(3.1%-6.3% vs 2.0%), mostly mild in severity and transient. Conclusion:In Chinese patients with T2DM who had insufficient glycemic control with diet and exercise only, oral semaglutide showed better glycemic control at doses of 3, 7, and 14 mg and more weight loss at doses of 7 and 14 mg compared to placebo, with a safety profile consistent with that observed in the global trial population.

Objective:To examine the association between height loss and calcaneus bone mineral density (BMD) through data gathered from the China Kadoorie Biobank (CKB).Methods:The present study included 24 231 participants who attended the CKB resurvey during 2013-2014, in which calcaneus BMD was measured by quantitative ultrasound method for the first time. Height loss was calculated according to the differences appeared in height measurement between baseline and resurvey. We used linear regression models to estimate the association between height loss and BMD measures.Results:The mean interval between baseline and resurvey was (8.0±0.8 ) years. 33.0 % of the participants showed a height loss of ≥1.0 cm, and another 3.7 % were with height loss of ≥3.0 cm. After adjustment for potential confounders, there was a linear correlation seen between height loss and BMD ( P for all linear trend were <0.001). The βs (95 %CIs) for each 1.0 cm of height loss were -0.79 (-0.95--0.63) for broadband ultrasound attenuation (BUA), -2.74 (-3.35--2.13) for speed of sound (SOS), and -1.29 (-1.54--1.04) for stiffness index (SI). Compared with participants with stable height, the multivariate-adjusted βs (95 %CIs) for those with height loss of ≥3.0 cm were -3.29 (-4.08--2.50) for BUA, -10.70 (-13.66--7.73) for SOS, and -5.16 (-6.36--3.96) for SI, respectively. According to the subgroup analyses, the association of height loss with BMD measures seemed to be more apparent among females, in those aged ≥55 years, and those being less physically active. Conclusions:BMD became lower with the increase of height loss. Regular height measurement may contribute to the early diagnosis and prevention of osteoporosis.

OBJECTIVE To analyze the effects of tigecycline on coagulation function in patients with severe renal insufficiency， and to provide a reference for safe clinical drug use. METHODS Retrospective analysis was performed for the clinical data of patients with severe renal dysfunction complicated with infection receiving tigecycline admitted to nephrology department of our hospital from January 2021 to October 2022. The levels of prothrombin time （PT）， activated partial thromboplastin time （APTT）， international normalized ratio （INR）， platelet （PLT） and fibrinogen （FIB） were compared 3 days before medication， with 1-5， 6-10， 11-15 and 16-20 days after medication， 5 days after withdrawal and/or after symptomatic treatment. RESULTS Finally， 14 patients were included， and 9 patients developed coagulopathy， with an incidence of 64.29%. Compared with 3 days after medication， the levels of FIB at 6-10 and 11-15 days after medication， and PLT at 1-5 ， 6-10 and 11- 15 days after medication were decreased significantly， while the levels of PT at 1-5 and 6-10 days after medication， APTT at 1-5， 6-10 and 11-15 days after medication were significantly prolonged， and INR increased significantly at 1-5 and 6-10 days after medication （P＜0.05）. Compared with 3 days before medication， there were no statistically significant changes in FIB， PT， INR， APTT and PLT at 16-20 days after medication and 5 days after withdrawal and/or symptomatic treatment（P＞0.05）. CONCLUSIONS Patients with severe renal insufficiency should be cautious with tigecycline， which can lead to prolonged PT and APTT， increased INR， and decreased PLT and FIB. If medication time is over 14 days， dynamic monitoring of coagulation function indicators is recommended to reduce the risk of adverse reactions.