Minimal improvement in coronary artery disease risk prediction in Chinese population using polygenic risk scores: evidence from the China Kadoorie Biobank / 中华医学杂志(英文版)

BACKGROUND@#Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population.@*METHODS@#Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately.@*RESULTS@#In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model.@*CONCLUSIONS@#In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.

Genetic and healthy lifestyle factors in relation to the incidence and prognosis of severe liver disease in the Chinese population / 中华医学杂志(英文版)

BACKGROUND@#Severe liver disease (SLD), including cirrhosis and liver cancer, constitutes a major disease burden in China. We aimed to examine the association of genetic and healthy lifestyle factors with the incidence and prognosis of SLD.@*METHODS@#The study population included 504,009 participants from the prospective China Kadoorie Biobank aged 30-79 years. The individuals were from 10 diverse areas in China without a history of cancer or liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for incident SLD and death after SLD diagnosis associated with healthy lifestyle factors (smoking, alcohol, physical activity, and central adiposity). Additionally, the contribution of genetic risk for hepatitis B virus (HBV, assessed by genetic variants in major histocompatibility complex, class II, DP/DQ [ HLA - DP / DQ ] genes) was also estimated.@*RESULTS@#Compared with those with 0-1 healthy lifestyle factor, participants with 2, 3, and 4 factors had 12% (HR 0.88 [95% confidence interval [CI] 0.85, 0.92]), 26% (HR 0.74 [95%CI: 0.69, 0.79]), and 44% (HR 0.56 [95%CI: 0.48, 0.65]) lower risks of SLD, respectively. Inverse associations were observed among participants with both low and high genetic risks (HR per 1-point increase 0.83 [95%CI: 0.74, 0.94] and 0.91 [95%CI: 0.82, 1.02], respectively; Pinteraction = 0.51), although with a non-significant trend among those with a high genetic risk. Inverse associations were also observed between healthy lifestyle factors and liver biomarkers regardless of the genetic risk. Despite the limited power, healthy lifestyle factors were associated with a lower risk of death after incident SLD among participants with a low genetic risk (HR 0.59 [95%CI: 0.37, 0.96]).@*CONCLUSIONS@#Lifestyle modification may be beneficial in terms of lowering the risk of SLD regardless of the genetic risk. Moreover, it is also important for improving the prognosis of SLD in individuals with a low genetic risk. Future studies are warranted to examine the impact of healthy lifestyles on SLD prognosis, particularly among individuals with a high genetic risk.

Multimorbidity patterns and association with mortality in 0.5 million Chinese adults / 中华医学杂志(英文版)

BACKGROUND@#Few studies have assessed the relationship between multimorbidity patterns and mortality risk in the Chinese population. We aimed to identify multimorbidity patterns and examined the associations of multimorbidity patterns and the number of chronic diseases with the risk of mortality among Chinese middle-aged and older adults.@*METHODS@#We used data from the China Kadoorie Biobank and included 512,723 participants aged 30 to 79 years. Multimorbidity was defined as the presence of two or more of the 15 chronic diseases collected by self-report or physical examination at baseline. Multimorbidity patterns were identified using hierarchical cluster analysis. Cox regression was used to estimate the associations of multimorbidity patterns and the number of chronic diseases with all-cause and cause-specific mortality.@*RESULTS@#Overall, 15.8% of participants had multimorbidity. The prevalence of multimorbidity increased with age and was higher in urban than rural participants. Four multimorbidity patterns were identified, including cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), gastrointestinal and hepatorenal multimorbidity (gallstone disease, chronic kidney disease, cirrhosis, peptic ulcer, and cancer), and mental and arthritis multimorbidity (neurasthenia, psychiatric disorder, and rheumatoid arthritis). During a median of 10.8 years of follow-up, 49,371 deaths occurred. Compared with participants without multimorbidity, cardiometabolic multimorbidity (hazard ratios [HR] = 2.20, 95% confidence intervals [CI]: 2.14 - 2.26) and respiratory multimorbidity (HR = 2.13, 95% CI:1.97 - 2.31) demonstrated relatively higher risks of mortality, followed by gastrointestinal and hepatorenal multimorbidity (HR = 1.33, 95% CI:1.22 - 1.46). The mortality risk increased by 36% (HR = 1.36, 95% CI: 1.35 - 1.37) with every additional disease.@*CONCLUSION@#Cardiometabolic multimorbidity and respiratory multimorbidity posed the highest threat on mortality risk and deserved particular attention in Chinese adults.

Study on the experience of nurses in the operating room of general hospitals / 中国实用护理杂志

Objective:To describe the experience of nurses in general hospital operating room for specialist management.Methods:A questionnaire survey was conducted among 226 operating room nurses using the questionnaire of specialist nurses' work obstruction factors. Eighteen of the operating room nurses were interviewed by phenomenological research methods in qualitative research.Results:The obstacles to the professional management of nurses in the operating room were mainly reflected in the difficulty of doing only the work of specialist nurses (96.46%,218/226), "there is no clear role positioning (93.81%, 212/226)", and "responsible for the work of several departments(89.82%, 203/226)." The refinement and analysis of the interview data showed that the management of specialist equipment could not be arranged and managed in a coordinated manner; the surgeons were over-reliant on the specialist nurses; the problem of setting up the positions of the senior nurses was outstanding; the nurses who were not the specialists have insufficient competence. With the sense of belonging; specialist nurses would have a slack situation.Conclusions:There are still many problems in the implementation of specialist management in the operating room of general hospitals. It is suggested that the rotation training of the operating room nurses should be carried out from the fixed professional group, the standardized training and the establishment of the mobile nurse database should be set up to promote the smooth implementation of the specialist management of the nurses in the operating room of the general hospital.

Comparison of genetic damage in mice exposed to black carbon and ozone-oxidized black carbon / 北京大学学报(医学版)

Objective:To make an assessment on the genotoxicity caused by black carbon ( BC ) and ozonized black carbon (O3-BC).Methods: In this study, 74 healthy male ICR mice [weighed (28 ± 1.5) g] were randomly divided into 7 groups, including one phosphate buffer solution ( PBS) control group and six particles exposed groups by intratracheal instillation with either BC or O 3-BC at the doses of 50, 100, 200 μg/mouse, respectively.There were 12 mice in the groups of 200μg/mouse and 10 mice in others.The mice were sacrificed 24 h after four intratrachealinstillations .The activities of catalase ( CAT) in serum and the levels of malondialdehyde ( MDA) in lung tissue homogenate were measured . As the DNA damage mark , 8-hydroxyguanosine ( 8-OHdG ) in urine and serum were quantified with ELISA method.Micronucleus test was used for potential genotoxicity of BC and O 3-BC.Hematoxylin and eosin staining was used to stain lung paraffin section .Results:The mice were in good condition during instillation , and the liver coefficient of the test groups was significantly lower than that of the control group (P<0.05).The activities of CAT in serum significantly increased in the 100 μg/mouse and 200μg/mouse groups after being exposed to these two kinds of particles .The micronucleus rate in allthe BC and O3-BC exposed groups increased ( P <0.05), but there was no statistically significant difference among the groups in the levels of 8-OHdG in serum and urine and MDA in lung tissue homogenate .In-flammatory response was found in the lung tissue under the microscope after exposure to BC and O 3-BC. Conclusion:Intratracheal instillation of BC and O 3-BC induced increasing of oxidative stress and genetic damage in mice .But there was no significant difference between these two particles in toxicity .Whether the genotoxicity of O 3-BC is higher than that of BC or not is uncertain .Further research is needed .