Objective To construct a nonparametric proportional hazards (PH) model for mixed informative interval-censored failure time data for predicting the risks in heart transplantation surgeries. Methods Based on the complexity of mixed informative interval-censored failure time data, we considered the interdependent relationship between failure time process and observation time process, constructed a nonparametric proportional hazards (PH) model to describe the nonlinear relationship between the risk factors and heart transplant surgery risks and proposed a two-step sieve estimation maximum likelihood algorithm. An estimation equation was established to estimate frailty variables using the observation process model. I-spline and B-spline were used to approximate the unknown baseline hazard function and nonparametric function, respectively, to obtain the working likelihood function in the sieve space. The partial derivative of the model parameters was used to obtain the scoring equation. The maximum likelihood estimation of the parameters was obtained by solving the scoring equation, and a function curve of the impact of risk factors on the risk of heart transplantation surgery was drawn. Results Simulation experiment suggested that the estimated values obtained by the proposed method were consistent and asymptotically effective under various settings with good fitting effects. Analysis of heart transplant surgery data showed that the donor's age had a positive linear relationship with the surgical risk. The impact of the recipient's age at disease onset increased at first and then stabilized, but increased against at an older age. The donor-recipient age difference had a positive linear relationship with the surgical risk of heart transplantation. Conclusion The nonparametric PH model established in this study can be used for predicting the risks in heart transplantation surgery and exploring the functional relationship between the surgery risks and the risk factors.

Objective To construct a nonparametric proportional hazards (PH) model for mixed informative interval-censored failure time data for predicting the risks in heart transplantation surgeries. Methods Based on the complexity of mixed informative interval-censored failure time data, we considered the interdependent relationship between failure time process and observation time process, constructed a nonparametric proportional hazards (PH) model to describe the nonlinear relationship between the risk factors and heart transplant surgery risks and proposed a two-step sieve estimation maximum likelihood algorithm. An estimation equation was established to estimate frailty variables using the observation process model. I-spline and B-spline were used to approximate the unknown baseline hazard function and nonparametric function, respectively, to obtain the working likelihood function in the sieve space. The partial derivative of the model parameters was used to obtain the scoring equation. The maximum likelihood estimation of the parameters was obtained by solving the scoring equation, and a function curve of the impact of risk factors on the risk of heart transplantation surgery was drawn. Results Simulation experiment suggested that the estimated values obtained by the proposed method were consistent and asymptotically effective under various settings with good fitting effects. Analysis of heart transplant surgery data showed that the donor's age had a positive linear relationship with the surgical risk. The impact of the recipient's age at disease onset increased at first and then stabilized, but increased against at an older age. The donor-recipient age difference had a positive linear relationship with the surgical risk of heart transplantation. Conclusion The nonparametric PH model established in this study can be used for predicting the risks in heart transplantation surgery and exploring the functional relationship between the surgery risks and the risk factors.

Objective:To investigate the feasibility of application of non-fasting dyslipidemia cutoff values in community population.Methods:Self-control study was used. 839 physical examinees (292 males and 547 females) were recruited in clinical laboratory of Guang′an men Hospital from January to October 2018. The median (interquartile range) of age was 60 (54, 66) years. Blood samples were collected before and at 4 h after a standard breakfast. Comparison of fasting and postprandial lipoprotein levels was performed using Paired-Samples T Test or Two-Related-Samples Wilcoxon. The changes of 4-hour postprandial blood lipid levels and the percentages of postprandial dyslipidemia according to different stratification of fasting dyslipidemia were performed using one-way ANOVA and χ 2 test, respectively. Results:Compared with fasting, 4-hour postprandial total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) decreased slightly, postprandial triglyceride (TG) increased by 0.72 mmol/L, and postprandial remnant-like lipoprotein cholesterol (RLP-C) increased by 0.27 mmol/L ( t or Z values = 10.26,22.94,24.22,4.71,16.61,26.92,-23.58,-19.35, P<0.05, respectively). According to the non-fasting dyslipidemia cut-off values recommended by the European consensus, there were 10%, 16.6%, 10.1%, 12.3%, 30% and 34.9% of the population in the appropriate levels of fasting TC, LDL-C, HDL-C, non-HDL-C, TG and RLP-C distributed in elevated levels of postprandial, respectively. The changes of 4-hour postprandial TC, LDL-C, non-HDL-C and HDL-C increased with the elevation of fasting level ( F=9.50,6.18,8.07,3.86, P<0.01), and the maximum changes of TC≤3.5%, LDL-C≤6.8%, non-HDL-C≤2.9%, HDL-C≤6.3%; the change of 4-hour postprandial TG increased slightly first and then decreased significantly (51.3% vs. 57.9% vs. 39.2%, F=19.05, P<0.01); the change of 4-hour postprandial RLP-C decreased (50.8% vs. 33.2%, F=10.40, P<0.01). The cut-off values of 4-hour postprandial dyslipidemia were TC ≥5.1 mmol/L, LDL-C ≥3.2 mmol/L, HDL-C ≤0.9 mmol/L, non-HDL-C ≥4.0 mmol/L and RLP-C ≥1.0 mmol/L. The cut-off values of borderline elevated and elevated TG levels were ≥2.2 mmol/L and ≥3.4 mmol/L, respectively. Conclusions:The cut-off values of postprandial dyslipidemia including TC, LDL-C, HDL-C, non-HDL-C and RLP-C were preliminarily established in community population, which could be applied to the routine lipid profile evaluation in the physical examination population. And it might be needed that postprandial TG was managed hierarchically according to different cut-off values.

Objective:To analyze the virus genome mutation of mothers with C genotype HBV and explore its relationship with HBV intrauterine transmission.Methods:A total of 399 mothers carrying HBV and their newborns hospitalized in the obstetrics department of the Third People's Hospital of Taiyuan from 2011 to 2013 were selected. Necessary information about mothers and children was obtained through a questionnaire survey and medical records. HBV DNA and HBV serological markers were detected by quantitative fluorescence PCR and electrochemiluminescence. Within 24 hours after birth and before active/passive immunization, those with positive HBsAg and/or HBV DNA in femoral venous blood were determined as HBV intrauterine transmission. According to the requirements of cloning and sequencing, mothers' HBV DNA load should be ≥10 6 IU/ml. Among 54 cases of HBV intrauterine transmission, 22 pairs of mothers and their newborns meeting the requirements of cloning and sequencing were used as the intrauterine transmission group. The same number of mothers and their newborns without intrauterine transmission was selected as the random seed method's control group. After PCR amplification of HBV DNA, gene cloning, and sequencing, the gene mutation analysis of mothers with C genotype HBV was performed. Results:Among the 44 samples, 39 (88.63%, 39/44) were genotype C, 2 were genotype B, and 3 were mixed genotype B, and C. A total of 406 clone beads from 42 mothers with C genotype HBV were analyzed for gene mutation, including 204 in the intrauterine transmission group and 202 in the control group. The base substitution mutation rate of PreS1, S, C, and P regions in the HBV intrauterine transmission group were significantly lower than those in the control group ( χ 2 ranged from 8.67 to 40.73, P<0.05). The mutation rate of base deletion in PreC and X regions in the HBV intrauterine transmission group was lower than that in the control group ( χ 2 values were 17.82 and 34.78, P<0.001). Two clones in the X region had 31 bp insertion mutations between nt1644 and nt1645, and two clones had 27 bp insertion mutations between nt1649 and nt1650, all of which took place in the control group. Conclusions:The base substitution mutations in the PreS1, S, C, and P segments of the HBV genome in mothers with C genotype HBV were associated with the occurrence of intrauterine transmission of HBV. Deletion mutations in the PreC region, insertion and deletion mutations in the X region may reduce intrauterine transmission risk.

Objective:To investigate the feasibility of application of non-fasting dyslipidemia cutoff values in community population.Methods:Self-control study was used. 839 physical examinees (292 males and 547 females) were recruited in clinical laboratory of Guang′an men Hospital from January to October 2018. The median (interquartile range) of age was 60 (54, 66) years. Blood samples were collected before and at 4 h after a standard breakfast. Comparison of fasting and postprandial lipoprotein levels was performed using Paired-Samples T Test or Two-Related-Samples Wilcoxon. The changes of 4-hour postprandial blood lipid levels and the percentages of postprandial dyslipidemia according to different stratification of fasting dyslipidemia were performed using one-way ANOVA and χ 2 test, respectively. Results:Compared with fasting, 4-hour postprandial total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) decreased slightly, postprandial triglyceride (TG) increased by 0.72 mmol/L, and postprandial remnant-like lipoprotein cholesterol (RLP-C) increased by 0.27 mmol/L ( t or Z values = 10.26,22.94,24.22,4.71,16.61,26.92,-23.58,-19.35, P<0.05, respectively). According to the non-fasting dyslipidemia cut-off values recommended by the European consensus, there were 10%, 16.6%, 10.1%, 12.3%, 30% and 34.9% of the population in the appropriate levels of fasting TC, LDL-C, HDL-C, non-HDL-C, TG and RLP-C distributed in elevated levels of postprandial, respectively. The changes of 4-hour postprandial TC, LDL-C, non-HDL-C and HDL-C increased with the elevation of fasting level ( F=9.50,6.18,8.07,3.86, P<0.01), and the maximum changes of TC≤3.5%, LDL-C≤6.8%, non-HDL-C≤2.9%, HDL-C≤6.3%; the change of 4-hour postprandial TG increased slightly first and then decreased significantly (51.3% vs. 57.9% vs. 39.2%, F=19.05, P<0.01); the change of 4-hour postprandial RLP-C decreased (50.8% vs. 33.2%, F=10.40, P<0.01). The cut-off values of 4-hour postprandial dyslipidemia were TC ≥5.1 mmol/L, LDL-C ≥3.2 mmol/L, HDL-C ≤0.9 mmol/L, non-HDL-C ≥4.0 mmol/L and RLP-C ≥1.0 mmol/L. The cut-off values of borderline elevated and elevated TG levels were ≥2.2 mmol/L and ≥3.4 mmol/L, respectively. Conclusions:The cut-off values of postprandial dyslipidemia including TC, LDL-C, HDL-C, non-HDL-C and RLP-C were preliminarily established in community population, which could be applied to the routine lipid profile evaluation in the physical examination population. And it might be needed that postprandial TG was managed hierarchically according to different cut-off values.

OBJECTIVE: To explore the effects of lead exposure on inflammatory damage of hippocampus and cognitive impairment in diabetic rats. METHODS: The specific pathogen free(SPF) male healthy Wistar rats were randomly divided into control group and lead-exposed group. The SPF male Goto-Kakisaki Wistar rats rats were randomly divided into diabetes group and diabetes lead-exposed group, with 10 rats in each group. Rats in lead-exposed group and diabetes lead-exposed group were continuously exposed to lead acetate water with a mass fraction of 0.025% for 9 weeks. Rats in control group and diabetes group were given distilled water. The body weight and blood glucose level of rats were measured before lead exposure and at 1, 3, 5, 7 and 9 weeks after exposure. After the exposure, Morris water maze test was used to evaluate the learning and memory ability of rats. The lead levels in whole blood and hippocampal tissues were detected by inductively coupled plasma mass spectrometry, and the expression of mRNA and protein expression of inflammatory factors in hippocampal tissues of rats were detected by real-time fluorescence quantitative polymerase chain reaction and enzyme-linked immunoadsorption, respectively. RESULTS: At the end of lead exposure, the difference of body mass of rats in the diabetes group and the diabetes lead-exposed group was not statistically significant compared with that in the same group before exposure(all P values were >0.05); but the body mass of rats in these two groups was lower than that of the control group and the lead-exposure group(all P values were <0.05). The blood glucose levels of rats were higher in the diabetic group and the diabetes lead-exposed group than that in the control group and the lead-exposed group, respectively(all P values were <0.05). Morris water maze test showed that the escape latency of rats in the 1 st, 2 nd and 3 rd day were longer in diabetes group and the diabetes lead-exposed group than that in the control group and the lead-exposed group(all P values were <0.05). The number of times of crossing platforms were less in the lead-exposed group and the diabetes group than that of the control group(all P values were <0.05). The number of times of crossing platforms was more in the diabetes lead-exposed group than that in the other 3 groups(all P values were <0.05). The levels of lead in blood and hippocampus of rats were higher in the lead-exposed group than those in the control group(all P values were <0.05), and those in the diabetes lead-exposed group were higher than that in the other 3 groups(all P values were <0.05). The relative expression of mRNA of interferon-γ(ifn-γ) and interleukin(il)-6 in hippocampal tissues of rats was higher in the lead-exposed group and the diabetes group than that of the control group(all P values were <0.05). The relative expression of mRNA of tumour necrosis factor-α(tnf-α) and il-1β in the hippocampal tissues of rats was higher in the diabetes group than that of the control group and the lead-exposed group, respectively(all P values were <0.05). The relative expression of mRNA of ifn-γ, tnf-α, il-1β and il-6 in hippocampal tissues of rats was higher in the diabetes lead-exposed group than that of the other 3 groups(all P values were <0.05). The relative protein expression of IFN-γ, TNF-α, IL-4 and IL-6 in hippocampal tissues of rats was higher in lead-exposed group than that of the control group(all P values were <0.05). The relative protein expression of IFN-γ, TNF-α, IL-1β and IL-6 in hippocampal tissues of rats was higher in diabetes group than that of the control group(all P values were <0.05). The relative protein expression of IFN-γ, IL-1β and IL-6 in hippocampal tissues of rats was higher in diabetes group than that of the other 3 groups(all P values were <0.05). CONCLUSION: Diabetes can promote the lead accumulation in the blood and hippocampus of rats. The combined effect of lead exposure and diabetes can up-regulate the expression of pro-inflammatory cytokines in the hippocampal tissues of rats, aggravate the inflammatory response, and have a synergistic effect on the cognitive impairment in rats.

Objective:To analyze the clinical characteristics of neonatal enteroviral meningitis.Methods:A retrospective analysis was conducted on 87 cases with intracranical infection.The cerebrospinal fluid(CSF)samples of these neonates were collected and tested by polymerase chain reaction(PCR) for enterovirus.According to the results, the cases were divided into the positive group(55 cases) and negative group(32 cases). The clinical characteristics of the cases were collected.Results:The time in hospital of the positive group was shorter than the negative group[(9.5±5.2)d vs.(21.8±15.8)d, t=4.295, P<0.001]. The cure rates of the positive group was higher[96.4%(53/55) vs. 81.2%(26/32), χ2=3.872, P=0.049]. There was no death case in the positive group, while there were 3 death cases(9.4%, 3/32)in the negative group.In summer and autumn, the morbidity of the positive group was higher[96.4%(53/55) vs.62.5%(20/32), χ2=17.181, P<0.001]. In two groups, the most predominant clinical presentation was fever[90.9%(50/55) vs. 68.8%(22/32), χ2=6.962, P=0.008]. CSF examination results showed that white blood cells, the proportion of polymorphonuclear cell and CSF protein in the positive group were lower than those in the negative group, while the proportion of mononuclear cell and CSF glucose level in the positive group were higher( P<0.001). Blood and CSF cultures were negative in the positive group.There were 10 cases whose blood cultures and CSF cultures were positive in the negative group.Among them, there were 3 cases infected by group B streptococcus, 6 cases by E. coli, 1 case by Chryseobacterium meningosepticum.The prognoses of the CSF culture positive cases were poor.The abonormal cases detected by cerebral ultrasound, MRI and aEEG were fewer in the positive group( P<0.05). Conclusion:Enterovirus is the common pathogen of nonbacterial meningitis in summer and autumn in our region.The prognosis of enteroviral meningitis is better.Neonates with suspected clinical presentation, such as fever, should undergo PCR test to check CSF for enteroviru.

Objective:To establish the reference interval of serum triglyceride (TG) for 4 hours after meal in healthy middle and old people of Beijing community, and to provide the diagnostic basis for the judgment of dyslipidemia after meal.Methods:Selected 369 elderly people from January to October 2018 in the health examination of Guang′anmen Hospital of the Chinese Academy of Traditional Chinese Medicine. The subjects collected fasting venous blood samples in the morning the next day after fasting for 12 hours, then ate a standard breakfast that conformed to the local dietary habits, and collected venous blood samples again 4 hours after eating. Serum TG levels were measured 4 h after meal using AU5822 fully automatic biochemical analyzer and matching reagents. The comparison of postprandial TG between different age and sex groups was statistically significant using the nonparametric test of two independent samples, and the comparison between postprandial and fasting TG using the nonparametric test of two paired samples with P<0.05 as the difference. The 95% confidence interval was calculated using a nonparametric method according to the relevant requirements of the CLSI EP28-A3c file, and the reference interval was expressed as P2.5, P97.5. Results:The median 4-hour post-prandial TG of the middle-aged and elderly aged 45-59 years and those aged ≥ 60 years at health checkups were 1.65 (1.25, 2.13) mmol/L and 1.58 (1.25, 2.00) mmol/L, there was no significant difference between the two groups ( Z=-1.040, P>0.05). There was no statistical difference between males 1.69 (1.22, 2.31) mmol/L and females 1.63 (1.26, 2.12) mmol/L at 4 hours postprandial TG levels in the 45-59 year-old group ( Z=-0.179, P>0.05),there was also no statistical difference between 1.64 (1.22, 2.06) mmol/L for men and 1.53 (1.28, 1.99) mmol/L for women aged 60 years or older ( Z=-0.256, P>0.05).Compared with the median fasting TG of 1.05 (0.87, 1.29) mmol/L, the median serum TG of 1.61 (1.25, 2.09) mmol/L at 4 hours after meal was significantly increased ( Z=-16.449, P<0.01). The difference between postprandial and fasting was 0.52 (0.30, 0.85) mmol/L.The reference range of serum TG at 4 hours after meal was 0.82 to 3.02 mmol/L. Conclusion:In this study, the reference range of serum triglycerides for 4 hours after meal was established in some healthy elderly population groups in Beijing.

Objective:To analyze the relationship between maternal mutations in basal core promoter region of hepatitis B virus (HBV) genotype C and intrauterine transmission.Methods:We collected information on general demographic characteristics and process of delivery among 399 pairs of consecutive HBsAg-positive mothers and their neonates, from the Third People’s Hospital of Taiyuan in Shanxi province, China. Fluorescence quantitative polymerase chain reaction (FQ-PCR) and Electro-chemiluminescence immuno-assay (ECLIA) kits were used to detect both maternal and neonatal HBV DNA and serological markers in the peripheral blood. From 113 mothers with HBV DNA load ≥10 6 IU/ml, we selected 22 mothers whose neonates were with intrauterine transmission and randomly selected the same number of mothers whose neonates were without intrauterine transmission, as controls. The whole-length HBV DNA were extracted, amplified, cloned, sequenced and genotyped. Finally, a total of 39 mothers with genotype C of HBV were selected for mutation analysis. Results:Thirty-nine cases of genotype C (88.63 %) were finally included in the study, with 19 cases in the intrauterine transmission group and 20 cases as controls. Rates of A1762T/G1764A double mutations were significantly different between the intrauterine transmission group and the control group (7.53 % vs. 27.72 %, P<0.001). Results from the multivariate analysis showed that the A1762T/G1764A double mutations had reduced the risk of intrauterine transmission (a OR=0.065, 95 %CI: 0.006-0.746, P=0.028). Maternal A1762T/G1764A double mutations appeared to be possibly associated with neonatal HBeAg ( P=0.050). Conclusion:A1762T/G1764A double mutations of HBV DNA from the genotype C of those HBsAg-positive mothers could reduced the risk of HBV intrauterine transmission during pregnancy.

OBJECTIVE:To provide reference for the establishment and improvement of work system for clinical pharmacist in PIVAS of our province even the country. METHODS:Questionnaire was conducted to investigate the PIVAS directors in the 65 third-grade class A hospitals in China,and the data was statistically analyzed. RESULTS:Totally 65 questionnaires were sent out, 63 were effectively received,with effective rate of 96.9%. 98.4% respondents thought PIVAS should equip clinical pharmacist,but the actual situation in respondent's hospital was not ideal. 100% thought clinical pharmacist in PIVAS should have the ability of prescription checking and prescription evaluation;more than 95% thought clinical pharmacist in PIVAS should assume the medi-cine publicity and education and need to have good communication with clinic;only 42.9% thought clinical pharmacist in PIVAS need to take part in the routine drug dispensing. CONCLUSIONS:It is necessary to equip clinical pharmacist with professional training in PIVAS. Clinical pharmacist in PIVAS should focus their ability on prescription checking and evaluation,medicine public-ity and education,communication with clinic.