1.Standardized methods for bone marrow micronucleus test in rodents and historical data collection
Hairuo WEN ; Jie SONG ; Zhihui MAO ; Jian GUO ; Xin WANG ; Yanping HU
Drug Evaluation Research 2017;40(5):638-641,647
In vivo Mammalian Bone Marrow Micronucleus Test is included in the standard battery genotoxicity testing,with great application prospects in medicine,public health,food and drug safety evaluation fields.Establishing standardized experimental methods and conditions in GLP condition and accumulating a certain range of background data could effectively ensure the reliability of the test system,and also provide strong basis to support the experimental data.We herein summarized the background data of mouse and rat bone marrow micronucleus tests performed from 2007 to 2015,to expound the standardized data collection method for rodent animal bone marrow micronucleus test.
2.Effects of Intra-articular Injection of Tranexamic Acid on Joint Swelling,Pain and Recovery of Joint Function in Patients with Simple Meniscus Injury
Mingjin LI ; Xiaohua CHEN ; Xiaoli TANG ; Cou LI ; Ting LIANG ; Hairuo WANG ; Fengling ZENG ; Ji WANG ; Xi LIU
China Pharmacy 2018;29(8):1098-1101
OBJECTIVE:To investigate the effects of intra-articular injection of tranexamic acid on joint swelling,pain and recovery of joint function in patients with simple meniscus injury. METHODS:A total of 62 patients with simple meniscus injury receiving arthroscopic surgery of the knee in orthopedics department of Chongqing people's hospital during Oct. 2016-Apr. 2017 were selected and divided into control group and observation group according to random table,with 31 cases in each group. Both groups received meniscus excision or trimming under knee arthroscopy. Control group was given intra-articular injection of 0.9%Sodium chloride injection 10 mL after wound suture. Observation group was given intra-articular injection of Tranexamic acid for injection 2.0 g added into 0.9% Sodium chloride injection 10 mL after wound suture. The drainage tube was not placed in all the patients,The tourniquet was loosened after the pressurized dressing of wound. Circumferential diameter of the knee and VAS scores of 2 groups were observed before surgery,1,3,5 and 7 d after surgery. Lysholm scores were observed before and one month after surgery. The occurrence of ADR was recorded. RESULTS:There was no statistical significance in circumferential diameter of the knee,VAS score or Lysholm score between 2 groups before surgery(P>0.05). 1,3,5 and 7 d after surgery,circumferential diameter of the knee in 2 groups was significantly bigger than before surgery,but the observation group was significantly smaller than the control group 1,3 d after surgery,with statistical significance(P<0.05). There was no statistical significance in circumferential diameter of the knee between 2 groups 5 and 7 d after surgery(P>0.05). VAS score of observation group 1,3 d after surgery and control group 1,3 and 5 d after surgery were significantly higher than before surgery,but the observation group was significantly lower than the control group 1,3,5 d after surgery,with statistical significance(P<0.05). There was no statistical significance in observation group 5,7 d after surgery and control group 7 d after surgery,compared to before surgery and 7 d after surgery(P>0.05).One month after surgery,Lysholm scores of 2 groups were significantly higher than before surgery,and the observation group was significantly higher than the control group,with statistical significance(P<0.05). No severe ADR was found in 2 groups during medication,and there also was not deep venous thrombosis after surgery. CONCLUSIONS:Intra-articular injection of tranexamic acid can effectively reduce the degree of early knee swelling after knee arthroplasty,relieve postoperative early pain.It promotes the recovery of knee function with good safety.
3.Pain management effect of quality control circle mode on patients with lower limb fractures
Xiaohua CHEN ; Xiaotao LONG ; Haolan XIONG ; Zexiang XU ; Wenjing SHAO ; Hairuo WANG ; Ting LIANG ; Fuming WANG
Chinese Journal of Trauma 2018;34(9):838-842
Objective To compare the pain management effects between painless wards with quality control circle mode and conventional pain management mode.Methods A retrospective case control study was conducted on the clinical data of 233 patients with lower limb fracture admitted from August 2015 to August 2016.There were 124 males and 109 females,aged 18-74 years [(48.3 ±3.3)years].The patients were divided into observation group (n =117) and control group (n =116) according to the pain management mode.The observation group followed the standard continuous quality improvement program and combined with professional team and patients Wechat group to implement pain management,and further measures were taken in accordance with the feedbacks.The control group adopted routine painless ward nursing model for perioperative analgesia nursing intervention.The pain score VAS,the start time of functional exercise,the compliance of rehabilitation activities,the length of hospital stay,and the healing time of fracture were compared between the two groups.Results There was no significant difference in VAS scores between the two groups at 12 hours before operation and 6 hours after operation (P > 0.05).The observation group had lower VAS scores at 12 hours (3.2± 1.4),24 hours (2.8 ±0.9),48 hours (1.6 ± 0.7),and 72 hours (1.5 ± 0.8) after operation than the control group (P <0.05).The observation group started functional exercises earlier [(18.9 ± 0.4) hours after operation]than the control group earlier [(48.1 ± 1.7) hours after operation] (P < 0.01).The observation group had a rehabilitation compliance rate of 62.6%,higher than that of the control group (17.6%) (P <0.05).The hospital stay [(12.18 ± 0.14) days] and fracture healing time [(97.86 ± 0.83) days] of the observation group were shorter than those of the control group (P < 0.05).Conclusion The pain management model of standardized continuous quality improvement can significantly relieve pain in patients with lower limb fracture,shorten hospitalization time,bring forward the start time of functional exercise,improve the compliance of rehabilitation activities,and promote fracture healing.
4.Study of Alkaline Comet Assay at Various Tissues in SD Rats with Intragastric Administration of Procarbazine Hydrochloride and Ethyl Carbamate
Hairuo WEN ; Gaofeng CHEN ; Lu REN ; Zhihui MAO ; Jie SONG ; Qi WANG
China Pharmacy 2019;30(1):26-30
OBJECTIVE: To evaluate the DNA damage response of procarbazine hydrochloride (PCZ) and ethyl carbamate (EC) to different tissues in rats by performing alkaline comet assay, to validate the feasibility of alkaline comet assay of various tissues. METHODS: Totally 30 SD rats were randomly divided into 6 groups according to body weight, with 5 rats in each group, such as negative control group (hyperpure water), PCZ 75 mg/kg group, PCZ 150 mg/kg group, EC 400 mg/kg group, EC 800 mg/kg group, positive control group (N-ethyl-N-nitrosourea 40 mg/kg). Those rats were given relevant medicine intragasttrically for 4 d; clinical symptoms of rats were observed and body weight was recorded during experiment. Within 3 h after last medication, the rats were sacrificed; liver, renal and lung weight were weighed; liver, kidney, lung and peripheral blood lymphocytes were collected. The single cell suspension was prepared to perform alkaline comet assay. After lysis, unwind, electrophoresis and dying, tail DNA% and tail distance of samples were analyzed by Komet 6.0 software. RESULTS: Compared with negative control group, body weight, liver and renal weight of rats were decreased significantly in PCZ 75 mg/kg group, PCZ 150 mg/kg group and positive control group 4 d after medication (P<0.05 or P<0.01). Body weight of rats were decreased significantly in EC 800 mg/kg 4 d after medication (P<0.05 or P<0.01); there was no statistical significance (P>0.05). Compared with negative control group, tail DNA% and tail distance in liver, kidney and peripheral blood lymphocytes were increased significantly in PCZ 75 mg/kg group, PCZ 150 mg/kg group and positive control group (P<0.05 or P<0.01); PCZ showed more significant effects on liver and lung. Tail DNA% and tail distance of liver, kidney and peripheral blood lymphocytes were increased significantly in EC 800 mg/kg group (P<0.05 or P<0.01), and tail DNA% and tail distance of renal tissue was increased significantly in EC 400 mg/kg group (P<0.05). CONCLUSIONS: PCZ induced stronger DNA damage; liver and lung are the major genotoxicity target of PCZ. EC-induced DNA damage is relatively weak, and kidney is the most sensitive organ for EC-induced genotoxicity.
5.Effect evaluation of perioperative management strategy for the elderly with hip fractures during pandemic of corona virus disease 2019
Xiaohua CHEN ; Zexiang XU ; Hairuo WANG ; Zhifeng HUANG ; Huixu MA ; Cou LI ; Xiaotao LONG ; Yongqing DING
Chinese Journal of Trauma 2020;36(3):207-211
Objective:To explore the perioperative management strategy for the elderly with hip fractures during the epidemic of corona virus disease 2019 (COVID-19) and evaluate its clinical effect.Methods:A retrospective case series study was conducted on 33 elderly patients with hip fractures admitted to Chongqing General Hospital, University of Chinese Academy of Sciences, from January 20 to February 29, 2020, including 14 males and 19 females, aged 65-92 years [(76.5±6.3)years]. There were 20 patients with intertrochanteric fractures and 14 with femoral neck fractures. In total, 15 patients were combined with hypertension and 9 with diabetes. A total of 19 patients were treated with open reduction and internal fixation and 14 with total hip/semi-hip replacement. The time from injury to admission was 2-14 hours. The temperature measurement, routine blood test and chest CT examination were performed to exclude COVID-19 in all patients, which showed 12 patients with pulmonary infection. The medical staff received different levels of protection: first level protection for those in the special ward, secondary level protection for the emergency isolation ward and tertiary level protection for those collecting the throat swab samples. The time from admission to operation, intensive care unit (ICU) stay time, hospitalization time, visual analogue score (VAS), perioperative complications as well as infection of patients and medical staff were observed and recorded.Results:The time from admission to operation was (3.18±0.19)days for all patients, with (2.24±0.28)days for 21 patients with no obvious pulmonary abnormality and (4.83±0.39)days for 12 with pulmonary infection. The hospitalization time was (10.97±0.31)days in all patients, with (9.71±0.27)days for 21 patients with no obvious pulmonary abnormality and (12.51±0.78)days for 12 with pulmonary infection. After operation, 12 patients were treated in ICU for 1-3 days, and the rest 21 patients were treated in general wards. The pain of all patients was effectively controlled. The time for exercise was (4.0±1.4)days after operation in all patients, among which 19 treated with fracture reduction and internal fixation started at (4.3±1.3)days after operation and 14 treated with total hip/semi-hip replacement started at (3.6±1.3)days after operation. VAS was (4.55±0.29)points at 12 hours before operation, (5.62±1.12)points at 6 hours, (3.54±0.39)points at 24 hours, and (2.42±0.11)points at 72 hours after operation ( P<0.05). Chest CT showed that the pulmonary inflammation was significantly improved one day before discharge. There was no indication of nucleic acid detection, with no urinary tract infection, pressure sore, deep vein thrombosis or other complications were found. No infection of patients or medical staff occurred. Conclusion:During pandemic of COVID-19, early surgical treatment for the elderly with hip fractures can be done in the general wards, based on strictly following the principle of infection prevention and control and carefully evaluating the perioperative risks, which can avoid the probability of infection of patients and medical staff without prolonging the hospitalization time or increasing the incidence of complications.
6.Study on in vitro and in vivo Genotoxicity of Emodin- 8-O-β-D-glucoside
Hairuo WEN ; Yujing YAN ; Jie SONG ; Rui AO ; Shuangcheng MA ; Qi WANG
China Pharmacy 2020;31(1):18-23
ABSTRACT OBJECTIVE:To evaluate the in vitro and in vivo genotoxicity of emodin-8-O-β-D-glucoside(EG),and to compare the difference of in vitro cell test and in vivo test of rats. METHODS:2D and 3D hepatocyte models were established by in vitro two-dimensional(2D)and three-dimensional(3D)cell culture. After modeling,2D and 3D hepatocyte were divided into blank control group(0.5% DMSO),mitomycin C group(positive control,0.1 μg/mL),EG low-dose,medium-dose and high-dose groups(10,50,200 μg/mL),respectively. The micronucleus ratio and tail DNA% of HepaRG cells were detected. SD rats were divided into blank control group(0.5% sodium carboxymethyl cellulose),ethyl methanesulfonate group(positive control,200 mg/kg),EG low-dose,medium-dose and high-dose groups(100,300,1 000 mg/kg),with 6 rats in each group. They were given medicine intragastrically for consecutive 15 d,once a day. 15 days later,the micronucleus formation rate of bone marrow polychromatic erythrocytes and hepatocytes,the tail DNA% and tail distance of peripheral blood lymphocytes and hepatocytes were measured. RESULTS:In the in vitro 2D HepaRG hepatocyte model,compared with blank control group,the micronucleus formation rate and tail DNA% of HepaRG cell were increased significantly in mitomycin C group (P<0.01). There was no statistical significance in micronucleus formation rate and tail DNA% of HepaRG cell among EG groups(P>0.05). In 3D HepaRG cell model, compared with blank control group, micronucleus formation rate and tail DNA% of HepaRG cell were increased significantly in mitomycin C group (P<0.01 or P<0.001), while tail DNA% of HepaRG cell wasincreased significantly in EG high-dose group(P<0.01). In the in vivo test,compared with blank control group,the micronucleus formation rate of bone marrow polychromatic erythrocytes and hepatocytes,the tail DNA% and tail distance of peripheral blood lymphocytes and hepatocytes were all increased significantly in ethyl methanesulfonate group(P<0.01). Tail DNA% of peripheral blood lymphocytes was increased significantly in EG high-dose group (P<0.01). There was no statistical significance in the micronucleus formation rate of bone marrow polychromatic erythrocytes and hepatocytes,the tail DNA% and tail distance of hepatocytes among EG groups(P>0.05);with the increase of dose,there was an increasing trend. CONCLUSIONS:The results of this study suggest that in 2D cell model,EG not lead to chromosome breakage and DNA damage,but the long-term administration and repeated administration in vivo of 3D cell model show that EG has a certain risk of DNA damage,so the evaluation results of 3D HepaRG cell model are more similar to those of rats in vivo. KEYWORDS Emodin-8-O-β-D-glucoside;Genotoxicity;Two-dimensional culture;Three-dimensional culture;Rat;Micronucleus test