Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial / 中华心血管病杂志

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

Cosinor-rhythmometry for 24-h urinary sodium, potassium, creatinine excretion in the Chinese adult population / 中华医学杂志(英文版)

BACKGROUND@#The low accuracy of equations predicting 24-h urinary sodium excretion using a single spot urine sample contributed to the misclassification of individual sodium intake levels. The application of single spot urine sample is limited by a lack of representativity of urinary sodium excretion, possibly due to the circadian rhythm in urinary excretion. This study aimed to explore the circadian rhythm, characteristics, and parameters in a healthy young adult Chinese population as a theoretical foundation for developing new approaches.@*METHODS@#Eighty-five participants (mean age 32.4 years) completed the 24-h urine collection by successively collecting each of the single-voided specimens within 24 h. The concentrations of the urinary sodium, potassium, and creatinine for each voided specimen were measured. Cosinor analysis was applied to explore the circadian rhythm of the urinary sodium, potassium, and creatinine excretion. The excretion per hour was computed for analyzing the change over time with repeated-measures analysis of variance and a cubic spline model.@*RESULTS@#The metabolism of urinary sodium, potassium, and creatinine showed different patterns of circadian rhythm, although the urinary sodium excretion showed non-significant parameters in the cosinor model. A significant circadian rhythm of urinary creatinine excretion was observed, while the circadian rhythm of sodium was less significant than that of potassium. The circadian rhythm of urinary sodium and creatinine excretion showed synchronization to some extent, which had a nocturnal peak and fell to the lowest around noon to afternoon. In contrast, the peak of potassium was observed in the morning and dropped to the lowest point in the evening. The hourly urinary excretion followed a similar circadian rhythm.@*CONCLUSION@#It is necessary to consider the circadian rhythm of urinary sodium, potassium, and creatinine excretion in adults while exploring the estimation model for 24-h urinary sodium excretion using spot urine.

Comparative study on composition regularities of traditional Chinese medicine formulas for five kinds of ophthalmic diseases using association rules / 中草药

Objective: To analyze the composition regularities of the traditional Chinese medicine formulas (TCMFs) for treating five kinds of ophthalmic diseases, including swelling and pain of eyes, night blindness, pterygium, blepharitis marginalis and nebula based on the data mining methodology. Methods: A total of 1999 TCMFs for ophthalmic diseases were collected from the Dictionary of Chinese Medicine Prescriptions. Then frequency analyses and association rules analyses were conducted with the three indicators of support, confidence and lift based on the Apriori algorithm. Results: The diaphoretic drugs and heat-clearing drugs were the commonly used types of the traditional Chinese medicines (TCMs) for swelling and pain of eyes, pterygium and blepharitis marginalis. The heat-clearing drugs and tonifying drugs were the commonly used types of TCMs for night blindness and nebula. Coptidis Rhizoma was frequently used for swelling and pain of eyes, Schizonepetae Herba was for blepharitis marginalis, and Chuanxiong Rhizoma was for nebula. The latent association rules with significant lift included Margarita→Calamina for swelling and pain of eyes, Myrrha→Olibanum for pterygium, Notopterygii Rhizoma et Radix→Saposhnikoviae Radix for blepharitis marginalis, and Lithargite→Sal Ammoniac for nebula. Conclusion: Using association rules, the comparative study on the five kinds of ophthalmic diseases can reveal the similarities and differences of treatments for these ophthalmic diseases and explore the composition regularities of TCMs, which helps to explore the hidden value of TCMFs.

The Content of Statistical Requirements for Authors in Biomedical Research Journals / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Robust statistical designing, sound statistical analysis, and standardized presentation are important to enhance the quality and transparency of biomedical research. This systematic review was conducted to summarize the statistical reporting requirements introduced by biomedical research journals with an impact factor of 10 or above so that researchers are able to give statistical issues' serious considerations not only at the stage of data analysis but also at the stage of methodological design.</p><p><b>METHODS</b>Detailed statistical instructions for authors were downloaded from the homepage of each of the included journals or obtained from the editors directly via email. Then, we described the types and numbers of statistical guidelines introduced by different press groups. Items of statistical reporting guideline as well as particular requirements were summarized in frequency, which were grouped into design, method of analysis, and presentation, respectively. Finally, updated statistical guidelines and particular requirements for improvement were summed up.</p><p><b>RESULTS</b>Totally, 21 of 23 press groups introduced at least one statistical guideline. More than half of press groups can update their statistical instruction for authors gradually relative to issues of new statistical reporting guidelines. In addition, 16 press groups, covering 44 journals, address particular statistical requirements. The most of the particular requirements focused on the performance of statistical analysis and transparency in statistical reporting, including "address issues relevant to research design, including participant flow diagram, eligibility criteria, and sample size estimation," and "statistical methods and the reasons."</p><p><b>CONCLUSIONS</b>Statistical requirements for authors are becoming increasingly perfected. Statistical requirements for authors remind researchers that they should make sufficient consideration not only in regards to statistical methods during the research design, but also standardized statistical reporting, which would be beneficial in providing stronger evidence and making a greater critical appraisal of evidence more accessible.</p>

Electroversion in treatment of arrhythmia in a patient with Wolff-Parkinson-White syndrome and cervical spinal cord injury / 中华创伤杂志(英文版)

We report electroversion in treatment of atrial fibrillation (AF) and atrioventricular nodal reentry tachycardia (AVNRT) in a patient with Wolff-Parkinson-White syndrome and cervical spinal cord injury. At first, the patient sustained respiratory failure and weak cough reflex, thereafter repeated bronchoscopy was used to aspirate the sputum as well as control the pneumonia, which resulted in arrhythmia (AF and AVNRT). Two doses of intravenous amiodarone failed to correct the arrhythmia. After restoration of sinus rhythm by electroversion, he was successfully weaned from mechanical ventilation and discharged from the intensive care unit without recurrent arrhythmia.

Association of angiotensinogen gene M235T variant with hypertrophic cardiomyopathy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To evaluate the influence of the angiotensinogen(AGT) gene M235T variant on the prevalence and severity of hypertrophic cardiomyopathy(HCM).</p><p><b>METHODS</b>The authors conducted a case-control study on 152 subjects, including 72 HCM patients and 80 normal controls. Polymerase chain reaction(PCR) combined with restriction fragment length polymorphism(RFLP) was used to detect the M235T variant of AGT gene. Interventricular septum thickness, left ventricular posterior wall thickness and apical wall thickness were measured by means of M-mode echocardiography under two-dimensional guidance in the parasternal long-axis plane and apical two- and four-chamber views.</p><p><b>RESULTS</b>(1) The genotype distributions of AGT gene in both groups were in agreement with Hardy-Weinberg equilibrium. (2) The genotype distributions of the M235T variant differed significantly in HCM patients and controls(chi-square=6.090 P<0.05). The frequencies of TT genotype and T235 allele in HCM patients were higher than did the patients in controls(TT genotype 0.63 vs 0.45 OR=2.037 95%CI 1.064-7.899 P<0.05 T235 allele 0.78 vs 0.64 OR=1.990 95%CI 1.197-3.308 P<0.01). (3)The patients with the TT genotype had significantly greater mean left ventricular maximal wall thickness than did the patients with the MM and MT genotypes [(19.1+/-4.8) mm vs(15.3+/-2.6)mm and(16.2+/-5.1)mm F=4.261 P<0.05].</p><p><b>CONCLUSION</b>The variant M235T of the AGT gene is significantly associated with HCM in this population. The genotype TT or allele T might be a genetic risk factor for the development and extent of hypertrophy in HCM patients.</p>

Association of angiotensinogen gene M235T variant with essential hypertension / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the association of the AGT gene M235T variant with essential hypertension in Han population of Zhejiang Province.</p><p><b>METHODS</b>The study included 230 subjects: 116 hypertensive patients and 114 normotensive controls. Polymerase chain reaction (PCR) combined with restrictive fragment length polymorphism (RFLP) was used to detect the M235T variant of angiotensinogen (AGT) gene. Blood pressure, body height and weight, fasting blood glucose and serum lipid were measured in all subjects.</p><p><b>RESULTS</b>(1)The systolic blood pressure and diastolic blood pressure of hypertensive group were significantly higher than those of control group, while no significant difference was observed with regard to age, gender, body mass index, blood glucose, or lipid profile. (2)The genotype distribution of AGT gene in both groups was in agreement with Hardy-Weinberg equilibrium. (3)The genotype distribution of the M235T variant differed significantly in hypertensives and controls (chi(2)=6.966,P<0.05). The frequencies of genotype TT and T235 allele in hypertensives were higher than those in controls (TT genotype: 0.47 compared with 0.33, chi(2)=5.36,P<0.05; T235 allele: 0.71 compared with 0.60, chi(2)=6.179, P<0.05).</p><p><b>CONCLUSION</b>The molecular variant M235T of the AGT gene is significantly associated with essential hypertension in this population. The genotype TT or allele T235 might be a genetic risk factor for hypertension.</p>