Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.

ObjectiveTo evaluate the efficacy and safety of An'erning granules in the treatment of community-acquired pneumonia in children. MethodA randomized， double-blind， single-simulation， placebo-controlled trial was designed in this study. The children were randomly assigned into an observation group （An'erning granules combined with ceftriaxone sodium） and a control group （An'erning granules placebo combined with ceftriaxone sodium） according to the ratio of 2∶1. The disease cure rate was taken as the main indicator of efficacy， and the safety of An'erning granules was observed. ResultA total of 206 children （137 in the observation group and 69 in the control group） were included in this study. Before treatment， the age， sex， body height， body weight， diagnosis time of pneumonia， and symptom and sign scores had no significant differences between the two groups. After 8 days of continuous medication， the observation group［70.80%（97/137）］ had higher cure rate than the control group［56.52%（39/69）］（χ²=4.17，P<0.05） and total effective rate of chest X-ray ［97.98%（97/99）］ than the control group［86.27%（44/51）］ （χ²=12.98，P<0.01）. The observation group was superior to the control group in the alleviation of TCM syndrome under the condition of 0-3 g dose stratification on day 3 of medication （P<0.01）. The recovery time， time to complete fever abatement， time to fever abatement and expectoration alleviation， rate of conversion to severe case， and reduction in the frequency of antibiotic use showed no significant differences between the two groups. In terms of safety， 13 and 7 adverse events occurred in the observation group and control group， respectively， which were relieved or disappeared after drug withdrawal or symptomatic treatment and showed no significant difference between the two groups. ConclusionIntravenous drip of ceftriaxone sodium combined with An'erning granules is effective in the treatment of community-acquired pneumonia in children. It can accelerate the absorption of pulmonary inflammation， alleviate the clinical symptoms in a short time for young children or the children with mild symptoms， and is safe in clinical application.

Objective To study the effect of noise pollution on serum hormone and heat shock protein-70(Hsp-70)levels in rats. Methods Forty male Wistar rats were randomly divided into control group(normal), experimental group(further divided into 35,65 and 85 dB three groups), each group 10 animals, stimulated for 30 min once a day, continually stimulated for consecutive 20 days. On the 21st day of experiment,the serum noradrenaline(NA),testosterone (T),dopamine(DA)and Hsp-70 levels were determined by enzyme-linked immunosorbent assay(ELISA). Results Compared with the control group, the body weight of experimental group(35, 65 and 85 dB groups)was reduced by 23.45%,30.13%, and 35.64%, respectively The serum T and DA levels were decreased by 9.12%, 20.06%, 37.99% and 15.49%, 8.31%, 24.88%, respectively; while the serum NA and Hsp-70 levels were increased by 35.08%, 171.52%,197.86%, and 39.34%, 195.09%, and 285.25%, respectively. All the result showed a significant difference(P<0.01). Conclusions Noise pollution can significantly affect the serum levels of hormone and heat shock protein-70 expression in rats.

Objective: To conduct a preliminary evaluation for the usability of Carelink remote monitoring system by clinical physician. Methods: A total of 215 patients received cardiovascular implantable electronic devices (CIED) with Carelink remote monitoring function from 12 hospitals in China between 2012-01 and 2013-10 were prospectively enrolled. The patient's mean age was (62.3±14.3) years including 108 male and 107 female. There were 54 physicians completed questionnaire survey. Based on the type of CIED, the patients were divided into3 groups: PM (pace maker) group,n=110, ICD (implantable cardioverter defibrillator) group,n=54 and CRT (cardiac resynchronization therapy) group,n=51. The patients received routine hospital visit at 3 months of CIED implantation and meanwhile, they performed device data transmission at 3 and 6 months of Carelink remote monitoring. The time physician spent to evaluate data was collected at 3 months and the questionnaire survey was completed by physician at 6 months after CIED implantation. Results: All 54 physicians felt that Carelink remote monitoring system was simple to operate and easy to use. There were 147 patients ifnished hospital visit at 3 months after CIED implantation, the mean time for physician to evaluate data was (14.8±8.4) min; 150 patients ifnished Carelink remote monitor at 3 months after CIED implantation, the mean time for physician to evaluate data was (8.2 ±4.6) min,P<0.0001.Conclusion: Carelink remote monitoring system was easy to use, it may save time in follow-up study which with high satisfaction in clinical practice.

Objective To study the effect of maca extract on sport fatigue and its antioxidant effect.Methods 50 healthy male Wistar rats were randomly divided into control group (normal breeding,without swimming,equal amount of distilled water for gavage),simple swimming group (swimming,equal amount of distilled water for gavage),swimming and medicine group (divided into maca extract 4.0,8.0 and 16.0 g/(kg· bw) groups,respectively),10 rats in each group.All rats were freely swimming in the circulating water flow daily for 15 days.On the 16th day of experiment,liver tissue samples were collected.The liver lipid peroxide (LPO),superoxide dismutase (SOD),glutathione peroxidase (GSH-Px) and liver glycogen level were determined.Results When rats were administered with maca extract at the doses of 4.0,8.0,16.0 g/(kg· bw),respectively,the swimming time before sinking and the total swimming time were increased by 18.99%,64.46% and 90.69%,and 18.99%,56.23% and 94.72%,respectively,while the numbers of times of sinking were decreased by 27.44%,42.86%,64.11% (P<0.01),respectively,compared with the swimming rats without maca extract treatment.The LPO content in the liver of rats treated with maca extract 4.0,8.0,16.0 g/(kg· bw) were reduced by 31.31%,42.00% and 31.31%,respectively,while the levels of SOD,GSH-Px and liver glycogen were enhanced by 25.92%,31.82%,62.09%,12.33%,23.01%,46.36% and 17.83%,44.69%,62.99%,respectively,over those of rats without maca extract treatment.Conclusions Maca extract reduces the liver LPO level,increases liver glycogen level,improves the SOD and GSH-Px activity,therefore,plays a protective role in sport fatigue.

Objective To study the effect of low frequency electrical stimulation on hormone levels in organs of Chinese tree shrews after death.Methods Giving Chinese tree shrews low frequency electrical stimulation.At 0 h, 3 h, 6 h, 12 h, 18 h, 24 h, 36 h and 72 h after death, the thyroid, liver, spleen were taken,and the levels of endothelin (ET), atrial natriuretic factor( ANF) , thromboxane ( TX) were determined by RIA method.At 0 h after death, midbrain ventral tegmental area ( VTA) of Chinese tree shrews was taken to detect the c-fos expression.Results After electrical stimula-tion, ET, ANF, TX levels in the cadaver organs and VTA c-fos expression of Chinese tree shrews were significantly in-creased than in the control group.The contents were decreasing with the time after death.Conclusions Low frequency e-lectrical stimulation can induce the synthesis and release of hormones in organs and c-fos expression in brain tissue of Chi-nese tree shrews.

Objective To study the effect of low frequency electrical stimulation on blood hormone levels in differ -ent animals.Methods At 12 h, 24 h and 36 h after low frequency electrical stimulation to Chinese tree shrews , Wistar rats, and BALB/c mice, respectively, the blood noradrenaline (NA) and endothelin (ET) levels were determined by ra-dioimmunoassay ( RIA) .Results The blood NA and ET levels of electrical stimulation group were significantly higher than that in the control group (P <0.01).At 24 h after reserpine treatment, the same electrical stimulation was given. The NA, ET levels were significantly decreased compared with that in the electrical stimulation group (P<0.05 to 0.01). Different animals responded to the same electric stimulus differently , following the order of Chinese tree shrews >Wistar rats >BALB/c mice.Conclusions Low frequency electrical stimulation can promote the release of noradrenaline and en -dothelin in Chinese tree shrews , Wistar rats and BALB/c mice.Reserpine can reduce the stress induced by low frequency electric stimulation to the body .

Objective To study the effects of living environment conditions and animal-animal interaction on the blood hormone levels and psychological behavior in Chinese tree shrews .Methods Chinese tree shrews were raised in ca-ges of different space sizes or were administered reserpine for 15, 30, 60, 120, 180 days, respectively.Then the animals were anesthetized by ether inhalation , and blood samples were taken from the heart to detect the levels of blood testosterone (T), estradiol (E2), endothelin (ET), adrenaline (A) and noradrenaline (NA) by radioimmunoassay (RIA).Results 1.Chinese tree shrews were bred in large cage (D1group) or small cage (X1 group) for 15, 30, 60, 120, 180 days, re-spectively.Compared with the animals bred in the large cage (D1 group), the level of blood testosterone (T) was signifi-cantly reduced (P<0.01), and the levels of adrenaline , noradrenaline and endothelin were significantly increased in the small cage group (P<0.01 for all).2.The animals raised in small cages in close neighborhood with large cages for 15, 30, 60, 120, 180 days, respectively.The levels of testosterone, adrenaline and noradrenaline in the large cage group (X2 group) were significantly higher than those of the small cage group (X1 group) (P<0.01 for all).3.The adrenaline and noradrenaline levels were significantly lower in all the reserpine groups (P<0.01 for all).4.The animals bred in small cages (X1 group) and in small cages in close neighborhood with large cages showed sudden loss , reduced appetite, testicu-lar atrophy , penile prolapse and stress symptoms .The animals of the reserpine groups appeared gentle temperament , signif-icantly reduced activity and reduced appetite .However , after stopping the reserpine administration and feeding them in large cages , the animals gradually returned to normal behavior .Conclusion Both animals living environment conditions and animal-animal interaction may cause changes of blood hormone levels and psychological behavior in Chinese tree shrews.

Nutrient agar medium was exposed in 0.085-0.092 T static magnetic fields for 12 h. Then we densities the optical densities at lamda = 600 (OD600) of Escherichia coli, Staphylococcus aureus and Bacillus subtilis in different culturing stage. The results were compared with those of control group in the normal geomagnetic field. The OD600 values of experimental groups of these three kinds of aerobes were significantly higher than those of control groups from 3h to 9h. However, after 11 h, there was no remarkable difference regarding the OD600 values between the two groups. The dissolved oxygen content of nutrient agar medium was determined by microtitration. The dissolved oxygen of nutrient agar medium under static magnetic for 12h increased 15% in average and there was significant difference when compared with the control. The results showed that the ferro-magnetic fields increased the dissolved oxygen content of nutrient agar medium significantly. These findings suggest that the effects of static magnetic fields on Escherichia coli, Staphylococcus aureus and Bacillus subtilis are related to the dissolved oxygen.
Bacillus subtilis ; growth & development ; radiation effects ; Culture Media ; radiation effects ; Escherichia coli ; growth & development ; radiation effects ; Magnetic Fields ; Staphylococcus aureus ; growth & development ; radiation effects

Objective To investigate toxicity and teratogenic effect of Microula seed oil on embryo of rat.Methods 150 mature Wistar rats (100 females, 50 males) were selected with female∶ male = 2∶1 cage match. During the daily morning examination the sperm was discovered in the vagina as the zero day for conception.100 pregnant rats were randomly divided into 5 groups (n=20 in each group): treatment group (included 3 groups: to give Microula seed oil 2.5 g /kg, 5.0 g /kg, 10.0 g /kg body weight, ig, respectively), cyclophosphamide group(7 mg/ kg body weight, sc) and the edible oil group (to give dose, such as volume as Microula seed oil, ig). From the 7th day of pregnancy, the treatment group, the edible oil group were given intervention once a day for 10 days. From the 11th day of pregnancy cyclophosphamide group was given cyclophosphamide as intervention once a day, for 3 days. On the 20th day the pregnant rats were killed.Results The body weight of pregnant rats and the rate of live births were significantly higher in the Microula seed oil dose group than in the cyclophosphamide group (P<0.01), stillbirth rate and birth rate of absorption was significantly lower in the Microula seed oil dose group than in the cyclophosphamide group (P<0.01), and no significant difference from the edible oil group (P> 0.05); the fetal rat, body weight, body length, tail length in all groups of Microula seed oil was no significant difference from the edible oil group (P> 0.05). There was no malformation in appearance, viscera, bones in the treatment group and the edible oil group while there were 112 fetal rats with deformity in 140 in the cyclophosphamide group.Conclusion Microula seed oil at doses of 2.5 g /kg, 5.0 g /kg, 10.0 g /kg body weight had no significant role in the toxicity and teratogenicity on embryos of pregnant rats.