[Bivariate heritability estimation of resting heart rate and common chronic disease based on extended pedigrees].

OBJECTIVE: To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes. METHODS: The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables. RESULTS: The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120－0.407), 0.404 (95%CI: 0.135－0.673), and 0.799 (95%CI: 0.590－1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120－1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181－0.788, P<0.05). CONCLUSION: Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.

[Analysis of large deletion of phenylalanine hydroxylase gene in Chinese patients with phenylketonuria].

OBJECTIVE: To analyze the types and distribution of large deletion of phenylalanine hydroxylase (PAH) gene in Chinese patients with phenylketonuria (PKU). METHODS: On the basis of 953 PKU patients from Peking Union Medical College and Gansu Province Medical Genetics Center, which were detected by directed sequencing of PAH gene between 2006 and 2014. Multiplex ligation-dependent probe amplification (MLPA) of PAH gene was performed in 43 patients with one or two unknown genotypes. And the deletion breakpoints were characterized by Gap PCR-sequencing. RESULTS: Twenty-four large deletion/duplication alleles were found in 22 patients, accounting for 51.1%(24/47)of the 47 unknown mutations of the 43 patients.There were 6 different large deletions, including Ex1del3758 (n=10), Ex4_5del (n=4), Ex4_7del (n=3), Ex1del5329ins56 (n=3), Ex3del6599ins8 (n=2), and Ex4del (n=1); and 1 duplication was found (Ex12dup, n=1). The most common large deletions in Chinese patients were Ex1del3758 (21.3%), Ex4_5del (8.5%), and Ex4_7del (6.4%). CONCLUSIONS: Large deletion mutations of PAH gene are present in Chinese PKU patients. It's important to detect the large del/dup mutation, and there are different hotspot mutation genotypes in Chinese patients.

Impact of the free-vaccine policy on timely initiation and completion of hepatitis B vaccination in Fujian, China.

The extent to which the free-vaccine policy impacts the initiation and completion of a hepatitis B vaccine series is poorly understood. The aim of this study was to evaluate the impact of the free-vaccine policy on hepatitis B vaccination. A provincial survey was conducted in 2006 in Fujian Province, south-east of China, where the free-vaccine policy for hepatitis B was announced in 2002 and implemented in 2003. A total of 1628 children were investigated, and 1443 (88.6%) were included in this analysis. Among the children studied, 55.2% were vaccinated within 24 h of birth, and 76.1% completed the hepatitis B vaccine series on time. The rate of hepatitis B surface antibody positivity increased from 29.9% among children born in 1992 to 90.5% among children born in 2005, while the corresponding HBV infection rate decreased from 30.4% to 1.72%. Logistic regression indicated that, compared to children born between 1996 and 2001, the odds ratios (ORs) for timely initiation were 2.57 (95% confidence interval [CI], 1.71-3.84), 5.24 (95% CI, 3.26-8.43) and 9.06 (95% CI, 4.48-18.34) among children born in 2003, 2004 and 2005, respectively; the corresponding ORs for completing the vaccine series were 4.23 (95% CI, 1.97-9.10), 3.76 (95% CI, 1.81-7.82) and 4.94 (95% CI, 1.74-14.00) among children born in 2003, 2004 and 2005, respectively. Children with delayed vaccine initiation (>24 h after birth) were less likely to complete the vaccine series than those who received a timely first dose (OR = 0.02, 95% CI, 0.005-0.09). The impact of the free-vaccine policy on vaccine initiation and vaccine series completion did not differ by children's residence area (rural vs urban). As hypothesized, the odds of completing the vaccine series increased after the free-vaccine policy was announced in 2002 among children with delayed initiation (>24 h after birth) but not among those with timely initiation (≤ 24 h after birth). In conclusion, the free-vaccine policy significantly improved the timely initiation and completion of the vaccine series. The impact of this policy on completion of the vaccine series was larger among children with delayed vaccine initiation.

Comparative efficacy of biological treatments for moderate-to-severe psoriasis: a network meta-analysis adjusting for cross-trial differences in reference arm response.

BACKGROUND: Multiple biological therapies are approved for the treatment of moderate-to-severe psoriasis. OBJECTIVES: To assess the short-term efficacy of biological treatments for moderate-to-severe psoriasis via a network meta-analysis that adjusts for reference arm response rates. METHODS: Fifteen randomized trials of biological treatments for moderate-to-severe psoriasis were identified. Rates of response, assessed as 50%, 75% and 90% reductions in the Psoriasis Area and Severity Index (PASI), were compared using a network meta-analysis. To account for variation across trials, the model was adjusted for placebo responses, the relevance of which was assessed by testing its statistical significance, impact on model fit, and extent to which lack of adjustment confounded the efficacy estimates for biologics. RESULTS: Psoriasis Area and Severity Index 75 response rates for placebo arms ranged from 1·8% to 18·9%. The probability of achieving a PASI 75 response was 80·5% [95% credible interval (CrI) 74·8-85·7] with infliximab 5 mg kg(-1) ; 72·5% (95% CI 66·1-78·3) with ustekinumab 90 mg; 67·5% (95% CI 60·7-73·9) with ustekinumab 45 mg; 66·2% (95% CI 57·3-73·3) with adalimumab 40 mg; 51·9% (95% CI 45·7-58·4) with etanercept 50 mg; and 38·0% (95% CI 31·6-45·1) with etanercept 25 mg. Infliximab had the highest PASI 75 response. Adalimumab and both ustekinumab doses had significantly higher PASI 75 responses than both etanercept doses. There were no significant differences among adalimumab and ustekinumab doses. CONCLUSIONS: A model adjusted for reference arm response rates was found to fit clinical trial data significantly better than unadjusted models.

[Analysis on influencing factors that leading to nonspecific responses to indeterminate results of HIV antibodies].

Objective: To identify the influencing factors that leading to nonspecific responses to indeterminate HIV antibody tests, to provide scientific evidence for the differential diagnosis of HIV infection and control strategy. Methods: A case control study was conducted. The samples of HIV antibody indeterminate in confirmed Western blot (WB) tests, but were negative in HIV nucleic acid tests, were collected as HIV antibody indeterminate group from WB results of HIV confirmatory laboratories of Fujian province in 2015-2016. The general population matched group with HIV antibody screening negative samples and WB negative matched group with WB negative samples were selected as the two compared groups by matching gender and age from HIV antibody screening in Fujian province in the same period. Blood concentrations of hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibody, anti-treponema pallidum (TP) antibody, antinuclear antibody (ANA), anti-human T-cell leukemia virus (HTLV) antibody, and alpha-fetoprotein (AFP) were detected by using enzyme-linked immunosorbent assay (ELISA). χ(2) test and multivariate non-conditional logistic regression analysis were performed to identify the influencing factors that leading to nonspecific responses, to indeterminate HIV antibody tests. Results: A total of 13 WB band patterns were observed in 110 HIV antibody indeterminate samples, in which a single p24 band (58.18%, 64/110), a single gp160 band (17.27%, 19/110) and a single p17 band (7.27%, 8/110) were the three most common patterns. The positive rate of anti-TP antibody was significantly higher in HIV antibody indeterminate samples than general population control group and WB negative control group (10.91%, 12/110 vs. 1.77%, 4/226 and 3.64%, 4/110), compared with two control groups (χ(2)=13.627 and 4.314, P<0.05). The positive rate of AFP was significantly higher in HIV antibody indeterminate samples than general population control group (18.18%, 20/110 vs. 0.44%, 1/226, χ(2)=39.736, P<0.05), the different was not significant compared with WB negative control group (18.18%, 20/110 vs. 23.64%, 26/110, χ(2)=0.990, P>0.05) While no significant differences were found between HIV antibody indeterminate group and two control groups in terms of the positive rates of ANA, HBsAg, anti-HCV antibody or anti-HTLV antibody. Conclusions: The influencing factors that leading to nonspecific responses to indeterminate HIV antibody tests appeared complicate, and the anti-TP antibody positivity might be an influencing factor responsible for nonspecific responses to indeterminate HIV antibody tests.

[Fujian Tulou Family Cohort Study: study design and characteristics of participants and pedigrees in baseline investigation].

Objective: To describe the study design, the characteristics of participants as well as the pedigrees included in the baseline survey of Fujian Tulou Family Cohort Study. Methods: Fujian Tulou Family Cohort Study was a prospective open cohort study with a biological sample bank. A baseline survey was conducted in Tulou areas of Nanjing county in Fujian province from 2015 to 2018, including questionnaire survey, physical and biochemical indicators examinations, and blood sample collection in adults aged ≥18 years. In addition, family relationship of the participants was also recorded. The pedigree information of the juveniles under 18 years old were also collected. Results: The baseline survey included 2 727 individuals in two clans, of whom 2 373 (87.0%) were adults, and 2 126 participants completed questionnaires, physical examinations and biochemical tests. The average age of the 2 126 participants was (57.9±13.3) years, with 39.4% being males. The current smoking rates in male and female participants were 41.2% and 2.1%, respectively. The corresponding rates of current alcohol consumption were 19.0% and 2.6%. For common chronic diseases, the prevalence rates were 51.3% for hypertension, 9.7% for diabetes and 26.7% for hyperlipemia according to the self-reported disease diagnoses, health examination results and biochemical examination results in class Ⅱ or Ⅲ hospitals. Based on the family relationship information and genealogical data, 710 pedigrees were finally identified, consisting of 5 087 family members. The numbers of five, four, three, and two generations pedigrees were 3, 88, 238 and 381, respectively. The pairs of the first to the fifth degree relatives were 12 039, 2 662, 1 511, 202 and 31, respectively. Conclusion: The establishment of Fujian Tulou Family Cohort provides valuable resources for exploring the genetic risk factors, environmental risk factors and gene-environment interactions contributing to the risk of common chronic diseases.

[Analysis of dietary pattern and diabetes mellitus influencing factors identified by classification tree model in adults of Fujian].

Objective: To find out the dietary patterns and explore the relationship between environmental factors (especially dietary patterns) and diabetes mellitus in the adults of Fujian. Methods: Multi-stage sampling method were used to survey residents aged ≥18 years by questionnaire, physical examination and laboratory detection in 10 disease surveillance points in Fujian. Factor analysis was used to identify the dietary patterns, while logistic regression model was applied to analyze relationship between dietary patterns and diabetes mellitus, and classification tree model was adopted to identify the influencing factors for diabetes mellitus. Results: There were four dietary patterns in the population, including meat, plant, high-quality protein, and fried food and beverages patterns. The result of logistic analysis showed that plant pattern, which has higher factor loading of fresh fruit-vegetables and cereal-tubers, was a protective factor for non-diabetes mellitus. The risk of diabetes mellitus in the population at T2 and T3 levels of factor score were 0.727 (95%CI:0.561-0.943) times and 0.736 (95%CI: 0.573-0.944) times higher, respectively, than those whose factor score was in lowest quartile. Thirteen influencing factors and eleven group at high-risk for diabetes mellitus were identified by classification tree model. The influencing factors were dyslipidemia, age, family history of diabetes, hypertension, physical activity, career, sex, sedentary time, abdominal adiposity, BMI, marital status, sleep time and high-quality protein pattern. Conclusion: There is a close association between dietary patterns and diabetes mellitus. It is necessary to promote healthy and reasonable diet, strengthen the monitoring and control of blood lipids, blood pressure and body weight, and have good lifestyle for the prevention and control of diabetes mellitus.

Effect of differentiating agents on nucleolar organizer region activity in human melanoma cells.

A human cell line established from a metastatic melanoma had both multiple numerical and structural chromosome aberrations including one to two copies of a submetacentric marker chromosome with an insertion of an active nucleolar organizer region (NOR). Treatment of this cell line with retinoic acid (RA) induced morphologic differentiation and reduced the cellular saturation density concomitant with a significant decrease in Ag-NOR activity. RA-treated cells grown in the absence of this differentiating agent, however, displayed a return to normal Ag-NOR activity, indicating the effect of this chemical on ribosomal genes is reversible.

Direct chromosome analysis of 50 primary breast carcinomas.

Direct chromosome analyses were performed in 50 cases of primary breast carcinoma. Thirty-six cases had modal chromosome counts in the diploid range; the other 14 cases were polyploid. Of the 22 cases with detailed G-banding analyses, the most frequent structural changes involved chromosome 1 (15 of 22), 3 (13 of 22), and 6 (13 of 22). Deletion of chromosome 1p was noted in nine cases, and both 3p- and 6q- were noted in 10 cases.

[Effects on organ-development of mouse embryo by inhibiting NOR activity].

It is reported here that the NOR activity of mouse embryonic cells treated with BrdU in Vitro. The NOR activity could be recovered after incubating the cells in the BrdU-free medium. The inhibition of NOR activity in the early and mid-term gestation led to abnormal development as follows: the increase of fetus abortion in vivo and death rate of newborn offsprings, causing a congenital blindness in the newborn offsprings. The main reason for the blindness is a contamination of a plenty of the untransparent granules with a size of 0.3 micron in diameter from the epithelial cells. The relationship between the transcription of 18S and 28S rRNA genes and the embryonic organ development is also discussed in this paper.

[The experiment of tumor-inhibiting effect of green tea extract in animal and human body].

Green tea extract (GTE) inhibits obviously gastrointestinal malignant tumors in rats induced by N-methyl-N'-nitro-n-nitrosoguanidine (MNNG). The incidence of tumor was 93.3% in the MNNG positive control group, whereas 53.3% in the MNNG plus GTE group (P < 0.01). The percentage of inhibiting tumor growth was 88% (P < 0.001). N-nitrosoproline blockage test in 3 groups of 45 cases of patients from the highly prone to (gastric cancer people), examined with gastroscope and classified pathologically, revealed that GTE can block N-nitroso-proline synthesis in vivo, with blockage rate of 91% in superficial chronic gastritis (P < 0.001), 94% in intestinal metaplasia (P < 0.001) and 93% in atypical hyperplasia and gastric cancer (P < 0.001). Chemical analysis demonstrated that the main ingredients in GTE are catechols (with the content of 50%), vitamins and trace elements. The mechanism of GTE's cancer-inhibiting and cancer-preventing function might be that catechols combine with N-nitroso-compounds or resolve them, and reduce their carcinogenic activity. These results will be of great significance in preventing gastrointestinal cancer.

[Effect of Chinese green tea extracts on the human gastric carcinoma cell in vitro].

We have studied and found antitumor effects in Chinese green tea extracts (T-8750). By pharmacologic test, it showed anticancer actions against several kinds of tumors in NIH mice evidently. Clinical trials on the therapeutics effects against early stomach cancer showed very effective. In order to prove it's function to prevent cancer. The research results as follows: (1) In vitro, T-8750 (0.5-1 mg/ml) could inhibit the cell growth of SGC (stomach gastric cancer) significantly. The inhibition action are obviously within 12-24 hr. (2) T-8750 traversed the migration of cell line L1210 from G1 phase to S phase, the rate were (63%). (3) In vitro, the blocking effect of T-8750 on the nitrosation of morpholine-nitrite was (92.4%). (4) the effect of T-8750 scavenger harmful free radicals was (63%).

[Effect of Chinese tea extract on the immune function of mice bearing tumor and their antitumor activity].

The dynamic changes of cellular immune function and antitumor effect of GTE (green tea extract) in the BALB/c mice bearing EAC, HAC and S-180 tumor were investigated. Results showed that intraperitoneal injection GTE daily dose of 80mg/kg stimulate the proliferation of T-Lymphocyte S-180 tumor bearing mice, the 125-IudR incorporation value (cpm) of control group was 932 and that of GTE treated group increased to 2988. The Natural Killer cell's activity (cpm) of treated group was raised from 10.7% of control group to 41%. Daily dose 50mg/kg inhibited the EAC, HAC and the life span of GTE mice bearing EAC ascites tumor prolonged 128%. The GTE were effective on growth activity against mouse Ehrlich tumor at a dose of 500mg/kg by oral administration (P less than 0.05), the inhibition ratio being about 32%. The authors suggested the mechanism of antitumor effects of GTE possible included both cellular immune function and the inhibition of tumor growth.

Some perspectives on affordable healthcare systems in China.

Consistent with the global population trend, China is becoming an aging society. Over one-fifth of the world's elderly population (aged 65 and over) lives in China. Statistics show that the elderly populace in China constitutes 8% of the total population in 2006 and the percentage will be tripled to become 24% in 2050. As a result, there is inevitably an increase in the prevalence of chronic disease that accounted for almost 80% of all deaths in China in 2005. On the other hand, from 1978 to 2003, the total expenditure on healthcare in China increased from 11.02 billion RMB up to 658.41 billion RMB, and in terms of GDP, it is an increase from 3.04% to 5.62%. The annual average increase (12.1%) in healthcare investment is therefore even higher than the annual rate of GDP increase (9.38%) during the last two decades. Meeting the long-term healthcare needs of this growing elderly population and escalating healthcare expenditure pose a grim challenge to the current Chinese healthcare system and the solvency of state budgets. In fact, the healthcare services in China have become less accessible since the early 1980s when its costs soared up. The rising costs have prevented many Chinese people from seeking early medical care. The phenomenon has created a wide disparity in seeking healthcare between urban and rural areas. These trends are of particular concern to the elderly, who have higher healthcare needs yet lesser means to afford the services. Furthermore, according to the 3rd National Health Service Survey, 79.1% of rural residents and 44.8% of urban citizens did not have any form of medical insurance. Such a low percentage of coverage of medical insurance indicates that many people may not be able to afford medical services when they suffer from severe diseases. Therefore, there is a great need of a more effective and low-cost healthcare system. A new system that can allow multi-level, multi-dimensional and standardized healthcare services for urban and rural citizens is proposed based on the development of miniaturized, integrated, networked, digitalized, and smart (MINDS) medical devices. Different from the traditional healthcare systems, the new one should bridge individuals and hospitals through a four-layer (PHCH) system structure: wearable intelligent sensors and devices for p-Healthcare system (PHS), home healthcare system (HHS), community healthcare system (CHS), and hospital health information system (H2IS). This four-layer structure should ensure people be monitored by the new system as closely as it can, resulting in the novel transformation of the function of healthcare systems from symptoms treatment to early risk detection and prevention. The new system is of particular importance to the cost reduction of healthcare services. It can reduce the chance of individual providers taking advantage of the provider-patient information asymmetry to prescribe unnecessary or inappropriate (but profitable) care. It also allows people to self-monitor their health conditions at their convenience in an attempt to lighten the workload of doctors and nurses. Moreover, more people can benefit from the new system with much lower medical insurance fees due to the reduced risk of developing severe diseases through regular, long-term and effective monitoring of citizens' health conditions nation-wide.

Noninvasive estimation of blood pressure using photoplethysmographic signals in the period domain.

In order to detect hypertension at its early stage, blood pressure (BP) of an individual must be carefully monitored. Aiming to monitor BP noninvasively and continuously, this study examines a new feature, normalized harmonic area (NHA), which is extracted from photoplethysmoographic (PPG) signals in the period domain by using the discrete period transform (DPT). BP, pulse transit time (PTT), diastolic time (DT) and NHA were obtained from photoplethysmographic (PPG) signals in the period domain by using the discrete period transform (DPT). BP, pulse transit time (PTI), diastolic time (DT) and NHA were obtained from 28 subjects before and immediately after step-climbing exercise. It was found that NHA has more significant correlation wiith BP than PTT and DT in this study. The mean difference and standard deviation (Mean±SD) between the BP estimated from NHA and the reference BP obtained from a commercial oscillometric BP meter were 0.37±4.3 mmHg and 0.51±4.8 mmHg for SBP and DBP, respectively. The result indicate that NHA is potentially a useful indicator of arterial BP.

[Effect of ketamine on acupuncture analgesia].

There were different opinions about whether ketamine has an antagonistic effect on electroacupuncture (EA) analgesia. The aim of this paper was to investigate the effect of ketamine on EA. The rats were divided into three groups: 4 mg/kg, 20 mg/kg of ketamine in doses, and normal saline groups. Ketamine was injected peritoneally in dosage of 4 mg/kg and 20 mg/kg respectively. Tail flick latency (TFL) and vocalization threshold (VT) were taken as the indices of pain responses. Changqiang and Yaoshu acupoints were selected for electroacupuncture. It was observed that the analgesia effects of EA were attenuated after injection of ketamine either in 4 mg/kg group of 20 mg/kg group. The results indicate that 4 mg/kg or 20 mg/kg ketamine in doses has an antagonistic effect on EA analgesia, suggesting that attention should be paid to the dosage when ketamine is used for EA analgesia.

[Effect of electroacupuncture on nociceptive responses after topical application of bicuculline in the rat].

In this paper effect of EA on nociceptive responses after topical application of bicuculline on the cortical somatosensory area of rats was investigated. Changqiang and Yaoshu point were selected for electroacupuncture. The results showed that the effect of EA on tail flick latency elicited by radiant heat and vocalization threshold elicited by electrical stimulation of tails in rats were increased after topical application of bicuculline on the cortical somatosensory area bilaterally; whereas there were no statistically changes in tail flick latency and vocalization threshold when the drug was applied unilaterally. It suggests that the cerebral cortex is involved in the modulation of nociceptive responses at the level of the brain stem and the spinal cord.