Objective:To explore how to personalize lung cancer screening programs for prevention in Chinese populations based on individual genetic risk score.Methods:We constructed the lung cancer polygenic genetic risk score (PRS-19) based on the 19 previously published genetic variations, using 100 615 participants with genotyping data from the China Kadoorie Biobank (CKB). Using the 5-year absolute risk of lung cancer in a population (55 years old with at least 30-pack-year history of smoking) as reference, the trend of 5-year absolute risk in different genetic risk groups was calculated in smokers and non-smokers, respectively. Distribution curves of 5-year absolute risk were also described to determine the theoretical age or smoking dose when different genetic risk groups reached the reference values. Given the overall findings, the specific start age for lung cancer screening were suggested for different genetic risk groups.Results:The 5-year absolute risk of lung cancer was 0.67% in 55-year-old smokers with 30 packs per year in the CKB. Among smokers, 5-year absolute risk of participants increased as the genetic risk increased. Hence, it was recommended that people at high genetic risk should start screening earlier. For the highest genetic risk populations (the top 1% of PRS), the start age might be changed to 50 years old. If the start age remained at 55-year-old, the smoking dose should be set lowered in high genetic risk populations. For the highest genetic risk populations, they should be included in lung cancer screening regardless of the cumulative smoking exposure. Among nonsmokers, it was also valuable to screen people with high genetic risk, considering the start age of 62 for the highest genetic risk populations and 74 for the lowest genetic risk populations (the bottom 5% of PRS).Conclusions:PRS-19 can be effectively used in developing lung cancer screening program for individualized prevention in China. For smokers with high genetic risk, the recommended starting age and smoking dose could be lowered for lung cancer screening, and non-smokers with high genetic risk could also be included in the screening programs.

Objective To study the value of parameters of Transit-Time Flow Measurement(TTFM) as predictor and judge for one-year after coronary artery bypass transplantation in patency rate of vessel grafts .Methods Parameters of quantity of blood flow and the value of PI( pulsation index) were measured and recorded by intraoperative TTFM in CABG .One-year of follow-ing up, coronary artery CT or coronary angiography examination were accomplished.Results Our study include artery grafts 46(including LIMA grafts 44, RIMA graft 1 and radial artery graft 1) with the patency rate of grafts 91.3％ for one-year after CABG, and vein grafts 48 with the patency rate of grafts 66.7％ .There exists statistically significant difference between above two groups(P<0.001).High PI is independent risk factor(P =0.037) in patency rate of vessel grafts for one-year after CABG by binary logistics regression analysis but no other parameters have the statistical significance (P>0.05) .The results from logistic regression were summarized using the area under the ROC curve(AUC) .The pulsation index has been found hav-ing moderate judgment ability(P=0.016) for the dysfunction of grafts after CABG for one-year with optimal cut-off value of 2. 45.Conclusion Intraoperative high value of PI is the independent risk factor in patency rate of vessel grafts for one-year after CABG.

BACKGROUND AND PURPOSE: Large cohort studies on relationship between family history of stroke (FHS) and stroke risk are lacking in Asians. We aimed to systematically evaluate the association of FHS with stroke risk in a cohort study of 0.5 million Chinese adults. METHODS: Information about FHS was self-reported. The median follow-up time was 7.16 years and the end-point of follow-up was incident stroke, which was entered directly into the China Kadoorie Biobank system. Multivariate analyses were performed with Cox proportional hazards model, and interaction analyses were carried using likelihood-ratio tests. RESULTS: Compared with participants without FHS, the hazard ratio (HR) (95% confidence interval, CI) of stroke for participants with FHS was 1.50 (1.46-1.55). The HRs increased with the number of first degree relatives with stroke (HRs=1.41, 1.98 and 2.47 for 1, 2 and ≥3 relatives, respectively, P(trend) <0.001). The HRs were 1.57 (95% CI: 1.50-1.66) and 1.49 (95% CI: 1.45-1.54) for sibling history and parental history, respectively. Similar associations with offspring stroke risk were observed between paternal history (HR=1.48, 95% CI: 1.43-1.54) and maternal history (HR=1.49, 95% CI: 1.43-1.55). Moreover, significant interactions were detected between FHS and health-risk behaviors (tobacco smoking and alcohol drinking). CONCLUSIONS: FHS is an independent risk factor for stroke in Chinese. The more first degree relatives are affected by stroke, the higher are individuals’ risk of suffering from stroke. The management of the health-risk behaviors for reducing stroke should be highlighted, especially for the individuals with FHS.
Adult ; Asian Continental Ancestry Group ; China* ; Cohort Studies* ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Parents ; Proportional Hazards Models ; Risk Factors ; Siblings ; Smoke ; Smoking ; Stroke*

Objective To evaluate the value of GeneXpert MTB/RIF assay in the clinical diagnosis of tuberculosis and tuberculosis associated rifampin resistance. Methods A total of 851 patients admitted to the Guangxi Longtan Hospital from September 22, 2015 to May 25, 2016 were enrolled. The smear microscopic examination, solid culture test, and GeneXpert MTB/RIF assay was performed on each patient. Drug sensitivity test of rifampicin using proportion method was done on patients infected with mycobacterium tuberculosis isolated by solid culture, and rifampicin resistance detection was performed on GeneXpert MTB/RIF positive patients. Bacteriological positive consistency test was performed on GeneXpert MTB/RIF and solid culture, and rifampicin resistance detection was compared bwtween GeneXpert MTB/RIF and drug sensitivity using proportion method. Culture and drug susceptibility testing were used as the gold standard, and the MTB sensitivity and specificity of smear microscopic examination, solid culture, and GeneXpert MTB/RIF assay was compared. Results Culture was used as the gold standard. Compared with culture, the sensitivity, specificity, positive predictive value, and negative predictive value of GeneXpert MTB/RIF was 95.48%(211/241), 94.91%(559/569), 87.55%(211/241), and 98.24%(559/569) respectively. The sensitivity of Xpert MTB/RIF for culture positive smear positive specimens and culture positive smear negative specimens was 98.78% (162/164) and 85.96%(49/57) respectively. Drug susceptibility testing was used as the gold standard. Compared with drug susceptibility testing, the sensitivity, specificity, positive predictive value, and negative predictive value of rifampin resistance measured by GeneXpert MTB/RIF was 98.70%(152/154), 92.98%(53/57), 97.44%(152/156) and 96.36%(53/55) respectively. The consistency rate of GeneXpert MTB/RIF and solid culture was 93.83% (Kappa = 0.847), and that of GeneXpert MTB/RIF rifampin resistance detection and proportion method for drug sensitivity was 96.38% (Kappa = 0.904). Conclusions The GeneXpert MTB/RIF detection is easily operated with high sensitivity and specificity compared with smear microscopic examination and solid culture, and it also possesses good consistency with solid culture and traditional drug sensitivity. Moreover, it could also be applied to diagnose the resistance to rifampin, which is very promising in application.

Alzheimer's disease (AD) is a complex neurodegenerative disorder which seriously causes the dementia in elderly people and afflicts millions of people worldwide. Drug discovery for Alzheimer's disease therapy has been a hot research area and a big challenge, in which development of acetylcholinesterase (AChE) inhibitors design was the most active and some AChE inhibitors are commercially available for AD medication already. However, practical using of commercial AChE inhibitors showed their limited usefulness and related adverse effects. Thus, it is extremely urgent to find novel AChE inhibitors with higher potency and less adverse effects. Based on the accurate crystallographic studies about AChE, strategies for multi-binding site AChE inhibitors have been formed, followed by design of the multi-target directed ligands. In this review, the structures and binding modes of commercial AChE inhibitors were briefly discussed, together with the development of AChE inhibitor design for AD therapy: from multi-binding site inhibitors to multi-target directed ligands.

Objective To explore the application and efficiency of composite positioned sputum discharging for patients with chronic obstructive pulmonary disease,in order to provide a basis for clinical practice.Methods A total of 135 COPD patients were treated in our hospital from January 2008 to December 2009.All hospitalized patients were randomly divided into the observation group(68 cases)and the control group (67 cases)according to medical record number.The observation group received composite positioned sputum discharging,while the control group was given routine sputum discharging method.The treatment effects and patient satisfaction of the two groups were observed and compared.Results After treatment,the expectoration of the observation group was higher than the control group.The blood gas results showed that the PaCO2 concentration of the observation group was lower than the control group,while PaO2 wag higher,and the differences were statistically significant.The overall satisfaction degree of the observation group was far higher than the control group.Conclusions Composite positioned sputum discharging has better results and patient satisfaction than the traditional manual sputum discharging method.It should be widely used in clinical application.

Positive selection and differential selective pressure analyses were carried out to study Haemagglutinin (HA) genes of H9N2 influenza viruses from different hosts in this paper. Results showed that, although most positions in HAs were under neutral or purifying evolution, a few positions located in the antigenic regions and receptor binding sites were subject to positive selection and some of them were even positively selected at the population level. In addition, there were always some positions differentially selected for viruses from different hosts. Both selection pressure working on HA codons and positions differentially selected might account for the extension of the host range and adaptations to different hosts of H9N2 influenza viruses.

Human enterovirus 71 viruses have been long circulating throughout the world. In this study, we performed a positive selection analysis of the VP1 genes of capsid proteins from Enterovirus 71 viruses. Our results showed that although most sites were under negative or neutral evolution, four positions of the VP1 genes were under positive selection pressure. This might account for the spread and frequent outbreaks of the viruses and the enhanced neurovirulence. In particular, position 98 might be involved in neutralizing antibodies, modulating the virus-receptor interaction and enhancing the virulence of the viruses. Moreover, both positions 145 and 241 might correlate to determine the receptor specificity. However, these positions did not display much difference in amino acid polymorphism. In addition, no position in the VP1 genes of viruses isolated from China was under positive selection.

It has been suggested that HCN1 is primarily expressed in hippocampus, however little is known about its effects on spatial learning and memory. In the present study, we investigated the effects of non-specific HCN1 blocker CsCl on spatial learning and memory by using Morris water maze and in situ hybridization in mice. The results showed CsCl 160 mg/kg ip for 4 days, and the mean escape latency was 34 s longer than that of normal control (P<0.01). In hippocampal tissues, staining for the HCN1 mRNA was stronger in the DG and CA1 region of the hippocampus (P <0.05, P<0.05, when CsCl-administration group was compared with normal group). Our results suggested that CsCl could significantly affect the spatial learning and memory in mice, and HCN channel is involved in the process of learning and memory.

It has been suggested that HCN1 is primarily expressed in hippocampus, however little is known about its effects on spatial learning and memory. In the present study, we investigated the effects of non-specific HCN1 blocker CsCl on spatial learning and memory by using Morris water maze and in situ hybridization in mice. The results showed CsCl 160 mg/kg ip for 4 days, and the mean escape latency was 34 s longer than that of normal control (P＜0.01). In hippocampal tissues, staining for the HCN1 mRNA was stronger in the DG and CA1 region of the hippocampus (P ＜0.05, P＜0.05, when CsCl-administration group was compared with normal group). Our results suggested that CsCl could significantly affect the spatial learning and memory in mice, and HCN channel is involved in the process of learning and memory.