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.

Survey of dose-effect relationship in Chinese materia medica

The research on the dose-effect relationship in Chinese materia medica is delayed due to the complexity of its composition, multi-efficacy, multi-targeting and other factors. Many experts put forward relevant research ideas and methods and worked out more and more research results in literature, experimental and clinical categories because of the progress of statistical methods and scientific and technological means in recent years. In this paper, these results were preliminarily combed to show the basic situation of dose-effect relationship research in Chinese materia medica.

不同剂量醋酸奥曲肽对重症急性胰腺炎患者临床疗效的影响

目的 观察醋酸奥曲肽不同给药剂量对重症急性胰腺炎（SAP）患者临床疗效的影响.方法 选择2013年9月至2016年1月在吉林大学第一医院二部急救医学科治疗的SAP患者90例,将患者按给药剂量不同分为奥曲肽小、中、大剂量组,每组30例.3组均给予基础治疗,奥曲肽小、中、大剂量组在基础治疗的同时用微量输液泵分别将奥曲肽0.2、0.3、0.4 mg加入0.9%氯化钠注射液100 mL中持续静脉泵入,每12 h给药1次,共使用20 d.比较3组临床症状（如腹痛、恶心、呕吐）好转时间、血淀粉酶恢复时间、住院时间和临床疗效,以及休克、肾功能不全等各种并发症的发生率的差异.结果 随着药物剂量的增加,奥曲肽小、中、大剂量组的症状好转时间（d）逐渐减少（分别为5.0±1.2、3.0±1.2、2.8±1.2）;血淀粉酶恢复时间、住院时间均以中剂量组最短,且明显短于大、小剂量组〔血淀粉酶恢复时间（d）：4.5±1.0比6.0±1.0和4.6±1.0,住院时间（d）：12.0±1.5比15.0±1.5和12.5±1.5〕;总有效率以中剂量组最高,高于大、小剂量组〔96.7%（29/30）比93.3%（28/30）和83.3%（25/30）;并发症发生率以小剂量组最高,高于中、大剂量组〔26.67%（8/30）比10.0%（3/30）和13.3%（4/30）〕.结论 采用微量输液泵静脉泵入奥曲肽,应用中等剂量的药物效果优于小剂量药物,而与大剂量组比较,效果无明显差异.

Progress in the Research of Radix Astragali in Treating Chronic Heart Failure:Effective Ingredients,Dose-Effect Relationship and Adverse Reaction

Radix Astragali,a Chinese herbal medicine possessing important cardiovascular pharmacologic effects,is widely applied for the treatment of chronic heart failure（CHF） in clinical practice.This paper summarizes briefly the researches in the last 10 years on its chemical compositions,effective ingredients for improving cardiac function,dose-effect relationship in treating CHF,and adverse reactions that occurred in clinical practice.

Overall assessment of antibiotic substitutes for pigs:a set of meta-analyses

Background:Antibiotic growth promoters are widely used to improve weight gain.However,the abuse of antibiotics can have many negative effects on people.Developing alternatives to antibiotics is an urgent need in livestock production.We aimed to perform a meta-analysis and network meta-analysis(NMA)to investigate the effects of feed additives as potential antibiotic substitutes(ASs)on bacteriostasis,growth performance,intestinal morphology and immunity.Furthermore,the primary,secondary,and tertiary ASs were defined by comparing their results with the results of antibiotics.Results:Among 16,309 identified studies,37 were summarized to study the bacteriostasis effects of feed additives,and 89 were included in the meta-analysis and NMA(10,228 pigs).We summarized 268 associations of 57 interventions with 32 bacteria.The order of bacteriostasis effects was as follows:antimicrobial peptides(AMPs)≈antibiotics>organic acids>plant extracts>oligosaccharides.We detected associations of 11 feed additives and 11 outcomes.Compared with a basal diet,plant extract,AMPs,probiotics,microelements,organic acids,bacteriophages,lysozyme,zymin,and oligosaccharides significantly improved growth performance(P<0.05);organic acids,probiotics,microelements,lysozyme,and AMPs remarkably increased the villus height:crypt depth ratio(V/C)(P<0.05);and plant extracts,zymin,microelements,probiotics,and organic acids notably improved immunity(P<0.05).The optimal AMP,bacteriophage,lysozyme,microelements,oligosaccharides,organic acids,plants,plant extracts,probiotics,and zymin doses were 0.100%,0.150%,0.012%,0.010%,0.050%,0.750%,0.20%,0.040%,0.180%,and 0.100%,respectively.Compared with antibiotics,all investigated feed additives exhibited no significant difference in effects on growth performance,IgG,and diarrhoea index/rate(P>0.05);AMPs and microelements significantly increased V/C(P<0.05);and zymin significantly improved lymphocyte levels(P<0.05).Furthermore,linear weighting sum models were used to comprehensively estimate the overall impact of each feed additive on pig growth and health.Conclusions:Our findings suggest that AMPs and plant extracts can be used as primary ASs for weaned piglets and growing pigs,respectively.Bacteriophages,zymin,plants,probiotics,oligosaccharides,lysozyme,and microelements can be regarded as secondary ASs.Nucleotides and organic acids can be considered as tertiary ASs.Future studies should further assess the alternative effects of combinational feed additives.

Clinical Observations on the Dose-effect Relationship of Gegen Qin Lian Decoction (葛根芩连汤) on 54 Out-patients with Type 2 Diabetes

Objective: To observe the therapeutic effect of different dosages of Gegen Qin Lian Decoction (葛根芩连汤) on type 2 diabetic patients. Methods: Fifty-four type 2 diabetic patients from low dosage group (20 cases), medium dosage group (19 cases) and high dosage group (15 cases) were treated with different dosage of Gegen Qin Lian Decoction for 12 weeks. Fasting blood-glucose (FBG), postprandial blood sugar (PBG) and Hemoglobin A1c (HbAlc) were determined before and after treatment. Results: With the increase of dosage, the overall effective rate of glycaemic control increased, and FBG, PBG, HbAlc decreased. The overall effective rate of blood glucose control of high dosage, medium dosage and low dosage group were 80%, 47%, 30% respectively, and there were significant differences between high dosage group and low dosage group. The decrease of FBG, PBG and HbAlc of high dosage showed significant differences from low dosage too. These data was analyzed by trend χ2 test and covariance analysis. Conclusion: The result indicated that different dosage of Gegen Qin Lian Decoction has dose-effect relationship in reducing HbAlc and FBG.

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.

The ED_(50)of Remazolam Toluenesulfonate Combined with a Subthreshold Dose of Esketamine for Inhibiting Cardiovascular Response to Tracheal Intubation in Elderly Patients

Objective:To explore the half-effective dose(ED_(50))of remazolam toluenesulfonate combined with subthreshold amounts of esketamine for inhibiting cardiovascular response to tracheal intubation in elderly patients.Method:We included 42 patients,aged 65-75,who required general anesthesia and single-lumen endotracheal intubation for elective surgery.The first patient was administered remazolam toluenesulfonate at a dose of 0.20 mg/kg.Once the patient lost consciousness,their alertness/sedation score(OAA/S score)was≤1,and their BIS score was≤60,and a subthreshold dose(0.3 mg/kg)of esketamine was given.The subsequent doses were adjusted using a sequential approach based on the cardiovascular response to tracheal intubation observed in the previous patient.The dose was modified in increments or decrements of 0.01 mg/kg.The ED_(50)and 95%CI of remazolam toluenesulfonate were calculated using the Dixon and Massey sequential distribution test method.Result:The inhibition of endotracheal intubation response was positively correlated with the dose of remazolam toluenesulfonate,and the depth of sedation could not be achieved when the amount was≤0.22 mg/kg.The ED_(50)of remazolam toluenesulfonate combined with a subthreshold dose of esketamine in inhibiting cardiovascular response to tracheal intubation in elderly patients was 0.30(0.28,0.33)mg/kg.There was no statistically significant difference in blood pressure between the induction of anesthesia and before the operation.Conclusion:When compounded with 0.3 mg/kg esketamine,the ED_(50)of Remazolam toluenesulfonate in inhibiting cardiovascular response to endotracheal intubation in elderly patients was 0.30 mg/kg(95%CI0.28-0.33 mg/kg).

Dose-dependent effects of pentabrominated diphenyl ethers on sexual hormone and histology of male reproductive system in rats

Polybrominated diphenyl ethers (PBDEs) used as flame retardants are widely used in a variety of consumer products, like textiles, foam and building materials. They are persistent in the environment, and increasing levels of PBDEs have been found both biota and human tissue samples. In the present study we examined the dose-dependent effects of pentabrominated diphenyl ether (PBDE-99) on the serum hormone and histology of reproductive system in male rats. 40 health 4-week-old SD rats were divided into 4 groups randomly. The treated rats were orally administered with BDE-99 at the dose of 60,120 or 180 mg/kg, while controls received equal volume of corn oil. We examined the changes of serum hormone levels, histopathology, and PCNA after 30 days exposure to BDE-99. With increasing doses of BDE-99, testis organ coefficient increased, serum hormone levels lower, PCNA positive expression reduced, and the degeneration of seminiferous epithelium were revealed in treated group. These indicators with significant dose-effect relationship showed that BDE-99 can reduce the serum sex hormone levels and cause severe degeneration of seminiferous epithelium.

不同参数电针对内源性阿片肽系统调节的量效关系

Endogenous opioid peptides(EOP)are the neurochemical basis of the anesthetic and analgesic effects of acupuncture,and the quantity of acupuncture stimulus can be controlled accurately by using electroacupuncture(EA).The present study explores the dose-effect relationship between EA with different parameters and the regulation of EOP system.In this paper,the intervention effects of EA on EOP system were specially discussed in terms of the single factor and the different combinations of the frequency,waveform and current intensity.This study shows that EOP system presents a frequency-response specificity.The low frequency of EA promotes the release of enkephalin,β-endorphin and endomorphin,the high one activates the dynorphin system selectively,and the intermediate frequency works on promoting the release of enkephalin andβ-endorphin,as well as dynorphin.Sparse-dense wave of EA may induce the release of enkephalin,β-endorphin,endomorphin and dynorphin,presenting a synergistic effect.However,the waveform of EA should be selected flexibly in clinical practice.Sometimes the better therapeutic effect can also be obtained with the continuous wave of EA.EOP system is involved in mediating appropriate intensity of EA,while the acupuncture effect generated by an extra strong EA stimulation refers to a kind of stress response of non-opioid mechanism.The different combinations of EA parameters result in various effects.The combination of EA parameters should be optimized in accordance with different diseases,which is valuable for guiding clinical practice and the development of EA therapy.

Clinical Effect of Astragalus Granule of Different Dosages on Quality of Life in Patients with Chronic Heart Failure

Objective：To explore the dose-effect relationship of Astragalus granule（AG） on improving the quality of life（QOL） of the patients with chronic heart failure（CHF）.Methods：Ninety CHF patients of Fei（肺）-qi deficiency and/or Xin（心）-Shen（肾） yang-deficiency syndromes were equally randomized divided with a random number table into three groups;they received the high（7.5 g）,moderate（4.5 g）,and low dosage（2.25 g） of AG orally taken twice a day,respectively,and 4 mg of perindopril tablet once a day for 30 successive days.The heart function grade,patients＇ left ventricular ejection fraction（LVEF） and walking distance in 6 min（6mWD） were measured before and after treatment,and the patients＇ QOL was scored by the Minnesota Questionnaire for QOL evaluation in the patients with CHF at the same time.Results：The heart function grades of all the three groups after treatment were improved compared with those before treatment,but the improvements in high-dose group and moderate dose group were better than that in the low dose group（P0.05）.LVEFs were increased significantly in all the three groups,but the improvements in the high-dose group（59.42%±7.50%） and moderate dose group（61.98%±6.82%） were better than that in the low dose group（51.45%±6.80%,P0.01）; the 6mWDs in the all groups were also significantly increased（P0.01）,up to 419.80136.23 m,387.15134.13 m, and 317.69±39.97 m,respectively;and Minnesota scores in them were lowered to 29.59±4.69 scores,35.74±5.89 scores,and 42.78±6.06 scores,respectively;comparisons in aspects on 6mWD and Minnesota score showed that the effectiveness with high dose is the most effective,moderate dose as the second,and low dose as the lowest（P0.01）.Conclusions：AG was sufficient to display an optimal effect on improving heart contraction at the moderate dose.In aspects of improving the QOL of CHF patients,the effectiveness of AG showed a dosedependent trend.It should be applied discriminatively depending on the actual condition of patients and the aim of treatment in clinic.