Chronic Toxicity of a Novel Recombinant Human Granulocyte Colony-stimulating Factor in Rats

Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group):four groups were treated with rhG-CSFa at 500,100,10,1 μg/kg,respectively,and one group was treated with vehicle only to serve as the control.The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks.During the course of the chronic toxicity study,the physical status,body weight,and food consumption were monitored.Half of the rats in each group (n=10) were sacrificed after the last rhG-CSFa administration,and the other half were sacrificed at five weeks after the last rhG-CSFa administration.Urinalyses,blood biochemistry,hematological analysis,histopathological examination,and immunological tests were performed for each of the rats.Results The hematological analyses revealed that the mean white blood cells count,neutrophils count,and neutrophils percentage were increased in male rats at the dose of 10 μg/kg or higher,and these were related with the biological activity of rhG-CSFa.Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 μg/kg,a dosage of 200 folds higher than the normal clinical dosage),but these abnormalities were recovered within 5-week recovery period.No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.

Primary investigation of dose-effect relationship of ^(153)Sm-EDTMP in treating multiple bone metastases

Objective:To calculate the focus absorption dose of 153Sm-EDTMP with the Monte Carlo(MC)EGS4 method for treatment of bone metastases from nasopharyngeal carcinoma or breast cancer,and investigate the relationship between the focus absorption dose and painkilling effect of 153Sm-EDTMP.Methods:Four patients with multiple bone metastases from nasopharyngeal or breast carcinoma and suffered from grade IV bone pain were treated with radionuclide internal irradiation of 153Sm-EDTMP.The absorption dose and dose distribution of bone metastases and other targeted organs were calculated with MC EGS4 program based on the time-order SPECT/CT scanning and the measurement of the radioactivity in the urine accumulation.The release of bone pain and the improvement of life quality were observed.Results:Bone pain of the patients was significantly alleviated to grade II for 3–4 weeks after internal 153Sm-EDTMP irradiation.The 3-dimensional absorption dose distribution image of bone metastases and targeted organs showed that the dose distribution in bone metastases was not asymmetrical.After injection of 0.65×37 MBq/kg 153Sm-EDTMP,the highest absorption dose in bone lesions was about 4.9–5.9 Gy,and the dose in the lesion margin was about 2.0 Gy.Using the highest dose as reference dose point,the relative absorption dose values of bone marrow,vertebra and sex organ near lesions were 0.48–1.1 Gy,0.51–0.85 Gy,and 0.01–0.14 Gy,respectively.Conclusion:The absorption dose of bone metastases is significantly lower than treatment dose of 30 Gy after single irradiation of 153Sm-EDTMP.The painkilling effect is limited and in accordance with clinical observation.

INFLUENCE OF SUCCINYLCHOLINE ON THE DOSE-RESPONSE RELATIONSHIP OF SUBSEQUENTLY ADMINISTERED ROCURONIUN

Objective To investigate the effect of succinylcholine on the dose-response relationship of sub-sequently administered rocuronium in healthy patients. Methods Forty-eight ASA physical status I-II patients,aged 17-65 years, scheduled for elective general surgery, were randomly assigned to either the rocuronium treat-ment group (R) or succinylcholine-rocuronium treatment group (SR). General anesthesia was induced with thio-pental 4 to 6mg/kg and fentanyl 2 to 5/μg/kg intravenously and maintained with 60% nitrous oxide in oxygen. Addi-tional doses of thiopental or fentanyl were administered as required. The dose-response relationship of rocuroniumwas determined by the single dose-response technique. In R group (n =24) , rocuronium was given after induction ofanesthesia. In SR group (n =24) , patients were intubated after 1. 5mg/kg of succinylcholine and rocuronium wasgiven after the complete recovery of neuromuscular blockade from succinylcholine. Patients were further randomlydivided into 4 subgroups receiving 150, 200, 250 or 300μg/kg of rocuronium respectively in both groups. Neuro-muscular function was assessed accelographically with train-of-four (TOF) stimulation at the wrist every 12s (usingthe TOF Guard? accelerometer). The relationship between probit-tranformed percentage depression of first twitchheight (Th) of train-of-four stimulation and logarithm dose of rocuronium was analyzed using linear regression.Results The dose-response curve of rocuronium after succinylcholine was shifted to the left in a parallel fashioncompared with that of rocuronium given alone. ED50 and ED95 of rocuronium were 193 ± 69 and 367 ± 73μg/kg re-spectively in R group, and 158 ±35 and 317 ±80μg/kg respectively in SR group (P <0.05). Conclusion Suc-cinylcholine shifts the dose-response curve of rocuronium to the left and potentiates the effects of the neuromuscularblockade by about 15% of subsequently administered rocuronium. Lower doses of rocuronium are required afterprior succinylcholine.

二氯甲烷职业接触内外暴露水平的关系研究

目的探讨职业接触二氯甲烷的生物接触限值。方法以50名职业接触二氯甲烷工人为接触组,另选择同一企业43名行政人员为对照组,检测工作场所空气中二氯甲烷水平,以及作业工人班末尿中的二氯甲烷水平,并进行两者间的相关分析,制订二氯甲烷的生物接触限值。结果班末尿中二氯甲烷水平与工作场所空气中二氯甲烷时间加权平均浓度具有相关性(决定系数为0.962,P<0.05),回归方程为y=0.001 1x+0.038 8(P<0.001)。结论劳动者职业接触二氯甲烷后尿中内暴露与外暴露之间存在剂量-效应关系,为制定我国职业接触二氯甲烷的生物限值提供了科学依据。

Clinical observation on the time-effect relationship of moxibustion for primary dysmenorrhea due to stagnation and congelation of cold-damp

Objective:To observe the time-effect relationship of moxibustion for primary dysmenorrhea(PD)due to stagnation and congelation of cold-damp,thus explore the optimal choice of moxibustion duration,and provide evidence for achieving satisfactory efficacy in moxibustion treatment.Methods:A total of 90 patients with PD due to stagnatin and congelation of cold-damp were divided into three groups by the random number table method,with 30 cases in each group.All the patients in the three groups were given moxibustion treatment at Guanyuan(CV 4),20 min in group A,40 min in group B and 60 min in group C.The changes in the pain measurement score in the three groups were observed after treatment.Results:After treatment,there were significant differences in the clinical efficacy among the three groups(P<0.05);the clinical efficacy was better in group B and group C than that in group A(P<0.05),and that in group B was better than that in group C(P<0.05).Besides,the pain measurement score changed significantly after treatment in the three groups(all P<0.05),and the between-group differences were also statistically significant(P<0.05);the pain measurement scores in group B and group C were lower than that in group A(P<0.05),and that in group B was lower than that in group C(P<0.05).Conclusion:Given the same stimulating frequency and intervention time of moxibustion,40-minute duration demonstrates relatively better efficacy for PD due to stagnation and congelation of cold-damp.

Research ideas and strategies on the dose-effect relationship of traditional Chinese medicine prescriptions and herbs

We discuss here the complexity of the doses of traditional Chinese medicine(TCM) prescriptions and herbs from different viewpoints,including the heterogeneity of drug quality,the flexibility of prescriptions,and the diversity of drug effects.Then,the corresponding research ideas and strategies are proposed.We can reveal the actual situation of clinical doses based on in-depth "real-world study" of the safety and effectiveness of TCM prescriptions,create an analytical method for dose-effect relationships in accordance with the features of TCM,and reveal the correlated regular nature of the effectiveness and dosage of TCM prescriptions and herbs.

A review of time-effect research on acupuncture in experimental rats/mice in the recent 10 years

Objective:To summarize the influence patterns of related time factors on acupuncture effectiveness in different disease model rats/mice,and to provide reference for acupuncture clinical practice.Methods:Retrieved the relevant literatures on time-effect experimental studies of acupuncture in rats/mice in the recent 10 years.The correlations between the key time factors(such as different intervention timings of acupuncture,acupuncture moments,operation durations,needle-retaining times,intervals and treatment courses)and the acupuncture effect were analyzed and summarized.Results:From the mainstream perspective of quantification,the earlier the acupuncture intervention,the better.The proper time to implement acupuncture varied depending on disease models and points.The best operation time varied widely between different diseases.The most frequently needle-retaining time was 20-30 min.The frequency of acupuncture was usually 1 time/day;the length of the treatment course was determined according to practitioners'experience.Conclusion:Throughout the time-effect studies of acupuncture intervention in experimental rats/mice,conclusions are inconsistent,especially the lack of quantitative research on acupuncture operation time,acupuncture frequency,acupuncture treatment duration,and optimal stimulation amount.Future research should explore and determine the best time-quantity parameters that affect the effectiveness of acupuncture intervention,which is the key and goal of the acupuncture time-effect research.Independent intervention-time experiments throughout the entire course of a single disease(dominant disease)need to be done to guide clinical and disciplinary development.

Effects of rolling manipulation with different durations on erector spinae muscle tonus and low back pain in patients with lumbar muscle strain

Objective:To observe the effects of rolling manipulation with different durations on erector spinae muscle tonus and low back pain in patients with lumbar muscle strain and to explore the best duration for rolling manipulation in treating lumbar muscle strain.Methods:A total of 75 patients who met the inclusion criteria were randomized into a 5-minute rolling manipulation group,a 10-minute rolling manipulation group,and a 15-minute rolling manipulation group using the random number table method,with 25 cases in each group.All three groups were treated with the same rolling manipulation,while the treatment time was 5 min,10 min,and 15 min,respectively.The treatment was performed 3 times a week for 2 consecutive weeks.The muscle tonus of bilateral erector spinae and visual analog scale(VAS)score for low back pain were compared among the three groups before and after treatment.Results:A total of 63 patients completed the study.Before treatment and after the last treatment,there were no statistical differences in the muscle tonus of the left erector spinae and right erector spinae among the three groups(P>0.05).After the last treatment,bilateral erector spinae muscle tonus dropped compared with the baseline in all three groups(P<0.01).Before treatment and after the last treatment,there were no significant differences in comparing the low back pain VAS score among the three groups(P>0.05).After the last treatment,the VAS score for low back pain in all three groups decreased(P<0.01).Conclusion:Under the condition that the forward swing force is 50-70 N,the backward swing force is 20-40 N,and the frequency is 138 times/min,the 5-minute rolling manipulation can significantly reduce the muscle tonus of erector spinae and relieve low back pain.