AIM:To introduce and evaluate two methods for sample size calculation in doseresponse research.METHODS:The methods used for sample size calculation in dose-response research include Cochran-Armitage trend(CAT) test proposed by Jun-mo Nam and the Unified contrast(CUC) method proposed by Chang. This paper takes the example of binary data,uses the two methods to calculate the required sample size and evaluate the power by simulation under the assumption that the response rate had a linear relationship with dosage under the logit scale.RESULTS:When the probability of response followed a linear trend on the logit scale, the sample sizes estimated from the two methods are approximately equal in various parameter's settings.The simulated power of CAT test was close to the expected one,however,the simulated power of CUC method was obviously affected by the values of contrast coefficient,if a contrast whose coefficients parallel the expected response, the CUC method was more powerful. CONCLUSION:When the probability of response follows a linear trend over dosage on the logit scale,the two methods reach almost the same result,in such circumstance,the Chang's unified contrast method will obtain an increasing power.

Objective To investigate the role of the percentage of the total cross-sectional area of small pulmonary vessels for the lung area (%CSA) from multi-slice CT (MSCT) in evaluating the severity of chronic obstructive pulmonary disease (COPD). Methods One hundred and sixty-six COPD patients and 166 normal subjects underwent chest MSCT scans and all data were analyzed retrospectively. COPD patients underwent pulmonary function tests (PFT), including forced expiratory volume in one second (FEV1%) and FEV1/forced vital capacity (FEV1/FVC), and were classified into mild (n=32), moderate (n=65), severe (n=69) groups according to pulmonary function results, respectively. The%CSA less than 5 mm2 and 5—10 mm2 for the lung area (%CSA<5 and %CSA5-10) of small pulmonary vessels were measured with Image J image-processing program. Comparison of%CSA<5 and%CSA5-10 between the COPD and control groups was perfomred using t test, and the comparison between the 3 COPD subgroups and control group were carried out using ANOVA test. The correlation between %CSA and PFT was evaluated by the Spearman rank correlation test. The sensitivity and specificity of %CSA to diagnose COPD and the best cutoff were calculated from areas under the ROC curves. Results %CSA<5 of COPD patients and control group were (0.56 ± 0.19)%and (0.82 ± 0.15)%(t=12.80, P<0.001), respectively.%CSA5-10 of the two groups were (0.19 ± 0.09)%and (0.33 ± 0.16)%(t=8.93,P<0.001), respectively. The AUC values of%CSA<5 and%CSA5-10 were 0.866 and 0.790, respectively. When the cut-off values of%CSA<5 and%CSA5-10 were 0.65%and 0.24%, the sensitivities and specificities were 88%and 71%, 76%and 81%, respectively. The mean values of%CSA<5 in mild, moderate and severe groups were (0.67±0.20)%, (0.61±0.16)%and (0.44±0.14)%, respectively (P<0.05). The mean values of %CSA5-10 in the three groups were (0.19 ± 0.06)%, (0.19 ± 0.10)% and (0.20 ± 0.08)%, respectively.%CSA5-10 in the three groups were of no significant difference (P>0.05). FEV1%and FEV1/FVC in COPD patients were (60.38±15.52)%and 57.95±22.27.%CSA<5 in COPD patients correlated positively with both FEV1%and FEV1/FVC (r=0.609 and 0.721, P<0.01, respectively).%CSA5-10 in COPD patients correlated positively with both FEV1%and FEV1/FVC (r=0.271 and 0.288, P<0.01, respectively). Conclusion The measurement of%CSA<5 and%CSA5-10 in MSCT images correlated with PFTs and%CSA<5, which may play an important role in evaluating the severity of COPD.

Objective To investigate the correlation between serum biochemical parameters and Parkinson's disease (PD) risk in the elderly.Methods The 277 inpatients with PD as PD group in Jiangsu Province Hospital from January 2009 to December 2013 were selected,at the same time,the 277 age and gender-matched healthy persons were enrolled as control group.The levels of total cholesterol (TG),total bilirubin (TB),uric acid (UA),low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected and compared between the two groups.Results The levels of TG,UA,TB,HDL-C and LDL-C were significantly lower in PD group than in control group [(4.35±1.13) mmol/L vs.(4.95±0.98) mmol/L,t=6.63;(278.00± 101.89)μmol/L vs.(380.90 ± 108.28) μmol/L,t =12.44;(13.02 ± 7.56) μmol/L vs.(17.39 ± 7.30)μmol/L,t=7.09;(1.26±0.37) mmol/L vs.(1.34±0.28) mmol/L,t=3.38;(2.59±0.79) mmol/L vs.(3.17±0.91) mmol/L,t=7.42,all P＜0.05].Logistic multiple regression analysis showed that the decreased levels of TB,UA and LDL-C were independently associated with prevalence risk of PD (OR=0.940,0.991 and 0.219,all P＜0.001).The combined score of TB,UA and LDL-C was constructed by using the linear weighted method.ROC curve was drawn to select the higher diagnostic validity index among TB,UA,LDL-C and combined score.The area under the ROC curve for TB,UA,LDL-C and combined score was 0.713,0.765,0.682 and 0.809 (all P＜0.001),and the value of combined score was the highest.Conclusions The decreased levels of TB,UA and LDL-C are independently associated with PD.They possess certain clinical value in evaluating the prevalence risk of PD.

Statistical P value and its threshold have been controversial worldwide for a while. Recent heated debate was triggered by two practical issues: unexplainable high false positive rate in biomedical research, and global misunderstood of "statistical significance" in scientific community. Thus, part of scientists suggests applying more stringent significance level (from 0.05 to 0.005), or even giving up the use of significance level. We believe that they are throwing the baby out with the bath water. These suggestions will not contribute to any improvement of this unfavorable situation but will lead the scientific decision-making to a more difficult and subjective corner. Scientists should use statistical P value and threshold only if they correctly understand the soul of statistics-uncertainty. Statistical significance is neither sole nor dominant criterion to measure the scientific value, but an honest assistant. Scientific decision-making should initiate from the scientific experimental design, followed by rigorous implementation and transparent analysis, and synthesize a variety of information to reach a tenable conclusion.

Mendelian randomization (MR) approach follows the Mendel′s law of inheritance, which is called "Parental alleles randomly assigned to the offspring", and refers to use genetic variants as an instrumental variable to develop causal inference between the exposure factor and the outcome from observational study. In recent years, with the rapid development of genome-wide association study (GWAS) and various omics data,the disclosure of a large number of aggregated data provides an opportunity for the wide application of MR approach in causal inference. We introduce three methods widely used in MR and then apply them to explore causal relationship between blood metabolites and depressive. The advantages and disadvantages of three methods in causal inference are compared in order to provide reference for the application of MR in observational studies.

OBJECTIVEThis paper is aimed to explore the adverse reaction condition of Shuanghuangli an injection with three common used signal detecting methods based on SRS database of Jiangsu province, and to evaluate the performance of three methods.

METHODThree methods would be used to detect the signals based on the SRS database of Jiangsu province. Consistency of the results of these three methods with that proved in descriptions was evaluated by Kappa test. The trend graph of the confidence intervals of several time points was used to demonstrate the trend of the signal.

RESULTThe PRR method was consistent with ROR method in high degree in any situation. The results of BCPNN method was close to PRR and ROR method only when the related report count was larger. PRR and ROR methods had higher false positive rate than BCPNN method.

CONCLUSIONPRR or ROR method is proposed for signal detecting when the report count is large. BCPNN method is proposed for trend demonstration of signal with graph.

AIM:To investigate the effect of L-arginine(L-Arg) on expression of bcl-2,bax mRNA during pulmonary ischemia and reperfusion injury(PIRI) in rabbits.METHODS: Single lung ischemia and reperfusion animal model was used in vivo.The rabbits were randomly divided into three groups: sham operated group(sham,n=12),ischemia-reperfusion group(I/R,n=12) and I/R+ L-arginine group(L-Arg,n=12).Changes of several parameters,which included apoptotic index(AI),wet to dry ratio of lung tissue weight(W/D) and index of quantitative assessment of histologic lung injury(IQA),were measured at 300 min after reperfusion in lung tissue.Meanwhile the location and expression of bcl-2,bax mRNA as well as the ratio of bcl-2 mRNA/bax mRNA were observed.The lung tissue was prepared for light microscopic and electron microscopic observation at 60,180 and 300 min after reperfusion.RESULTS: As compared with I/R group,in intima and extima of small pulmonary artery,alveoli,and bronchiole epithelia,the expression of bcl-2 mRNA and the ratio of bcl-2 mRNA/bax mRNA were increased,and the expression of bax mRNA was decreased in L-Arg treatment group.The values of AI,W/D and IQA showed significantly lower than that in I/R group at 180 minutes after reperfusion in lung tissue(P

Observational study of therapy efficacy comparison has been widely conducted to provide the additional efficacy evidence to support randomized control study. Statistical adjustment for unmeasured confounders is a major challenge in observational study of therapy efficacy comparison. This paper summarizes and evaluates the relative statistical methods. Currently, the most commonly used methods include instrumental variable, difference-in-differences (DiD) model and prior event rate ratio (PERR) adjustment. The instrumental variable method skill fully escapes unmeasured confounders through model structure, but it is not easy to obtain satisfied instrumental variables. Both PERR and DiD require the data prior to exposure which are not always collected in observational studies. Unmeasured confounders could result in new requirements and pose new challenges for statistical methods, which needs further study and improvement.

Objective:To observe heart rate circadian rhythm in patients with chronic kidney disease (CKD) stage 5 and to analyze the effects of parathyroidectomy (PTX) on heart rate circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients.Methods:A cross-sectional observation was performed in 213 patients with CKD stage 5 and 96 controls, and the patients were divided into those with severe SHPT (PTX group, n=70) and without severe SHPT (non-PTX group, n=143). Forty-six PTX patients were followed up prospectively. The baseline data were compared among these groups. Holter electrocardiogram was performed for each participant. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Multiple linear regression analysis was used to analyze the related factors of heart rate circadian rhythm in patients with CKD stage 5. Results:The 24-hour, daytime and nighttime mean heart rate in patients with CKD stage 5 were all higher than those in controls, especially in PTX group (all P<0.05). The night/day heart rate ratios of controls and CKD stage 5 patients were (0.81±0.08) and (0.91±0.08) respectively ( P<0.01). Correlation analysis showed 24-hour and daytime or nighttime mean heart rate in patients with CKD stage 5 were positively correlated with serum levels of phosphorus and ln(alkaline phosphatase), while nighttime mean heart rate and night/day heart rate ratio were positively related with serum intact parathyroid hormone level. After adjusting with postoperative follow-up period (median time: 10.9 months), 24-hour and nighttime mean heart rate, and night/day heart rate ratio in PTX patients all decreased significantly (all P<0.01). Conclusions:Heart rate is increased and circadian rhythm is abnormal in patients with CKD stage 5, which are related with mineral and bone disorder. PTX significantly decreases 24-hour and nighttime mean heart rate in severe SHPT patients, and improves the heart rate circadian rhythm.

Observational comparative effectiveness studies have been widely conducted to provide evidence on additional effectiveness and to support randomized controlled findings in research. Although this type of study becomes more important over time, challenges related to the common biases which stemmed from confounders, are difficult to control. This manuscript summarizes some statistical methods used on adjusting measured confounders that often noticed in research, regarding the observational comparative effectiveness. Useful traditional methods would include stratified analysis, paired analysis, covariate model and multivariable model, etc.. Unconventional adjustment approaches such as propensity score and disease risk score methods may also be used in studies, for matching, stratification and adjustment. A good study design should be able to control confounders. The limitations of all the post hoc statistical adjustment methods should also be fully understood before being appropriately applied in practical events.