OBJECTIVE: To explore the association between de novo mutations (DNM) and non-syndromic cleft lip with or without palate (NSCL/P) using case-parent trio design. METHODS: Whole-exome sequencing was conducted for twenty-two NSCL/P trios and Genome Analysis ToolKit (GATK) was used to identify DNM by comparing the alleles of the cases and their parents. Information of predictable functions was annotated to the locus with SnpEff. Enrichment analysis for DNM was conducted to test the difference between the actual number and the expected number of DNM, and to explore whether there were genes with more DNM than expected. NSCL/P-related genes indicated by previous studies with solid evidence were selected by literature reviewing. Protein-protein interactions analysis was conducted among the genes with protein-altering DNM and NSCL/P-related genes. R package "denovolyzeR" was used for the enrichment analysis (Bonferroni correction: P=0.05/n, n is the number of genes in the whole genome range). Protein-protein interactions among genes with DNM and genes with solid evidence on the risk factors of NSCL/P were predicted depending on the information provided by STRING database. RESULTS: A total of 339 908 SNPs were qualified for the subsequent analysis after quality control. The number of high confident DNM identified by GATK was 345. Among those DNM, forty-four DNM were missense mutations, one DNM was nonsense mutation, two DNM were splicing site mutations, twenty DNM were synonymous mutations and others were located in intron or intergenic regions. The results of enrichment analysis showed that the number of protein-altering DNM on the exome regions was larger than expected (P < 0.05), and five genes (KRTCAP2, HMCN2, ANKRD36C, ADGRL2 and DIPK2A) had more DNM than expected (P < 0.05/(2×19 618)). Protein-protein interaction analysis was conducted among forty-six genes with protein-altering DNM and thirteen genes associated with NSCL/P selected by literature reviewing. Six pairs of interactions occurred between the genes with DNM and known NSCL/P-related genes. The score measuring the confidence level of the predicted interaction between RGPD4 and SUMO1 was 0.868, which was higher than the scores for other pairs of genes. CONCLUSION Our study provided novel insights into the development of NSCL/P and demonstrated that functional analyses of genes carrying DNM were warranted to understand the genetic architecture of complex diseases.
Asians ; Case-Control Studies ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Humans ; Mutation ; Parents ; Polymorphism, Single Nucleotide ; Whole Exome Sequencing

With the progress of globalization, the public health emergencies represented by major infectious diseases have become a major challenge for the public health management in China. The article briefly describes the emergency response capability assessment tools in China, and introduces two emergency response assessment tools with complete content structure and wide application in the world. Then the advantages and disadvantages of the tools are compared and discussed in order to provide reference for improvement of the assessment tools for public health emergency response capability in China.
China ; Disaster Planning ; Humans ; Public Health ; Public Health Administration

Long-term repeated regular blood donation may result in the loss and deficiency of iron. Epidemiological studies have indicated that blood donation frequency, demographical characteristics, and genetic factors are associated with iron deficiency. Our review summarizes the progress in research of etiology of iron deficiency in blood donors and intervention measures to provide evidence for the health management of non-remunerated blood donors in China.
Blood Donors ; Ferritins ; Humans ; Iron ; Iron Deficiencies ; Risk Factors

Next-generation sequencing has revolutionized family-based association tests for rare variants. As the lower power of genome wide association study for detecting casual rare variants, methods aggregating effects of multiple variants have been proposed, such as burden tests and variance component tests. This paper summarizes the methods of rare variants association test that can be applied for family data, introduces their principles, characteristics and applicable conditions and discusses the shortcomings and the improvement of the present methods.
Computer Simulation ; Family Relations ; Genetic Association Studies ; Genetic Variation ; Genome-Wide Association Study/methods* ; Humans

Objective: To determine the impact of inflammatory reaction levels and the culprit plaque characteristics on preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow grade in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The is a retrospective study. A total of 1 268 STEMI patients who underwent pre-intervention optical coherence tomography (OCT) examination of culprit lesion during emergency PCI were divided into 2 groups by preprocedural TIMI flow grade (TIMI 0-1 group (n =964, 76.0%) and TIMI 2-3 group (n =304, 24.0%)). Baseline clinical data of the 2 groups were collected; blood samples were collected for the detection of inflammatory markers such as high sensitivity C-reactive protein (hsCRP), myocardial injury marker, blood lipid, etc.; echocardiography was used to determine left ventricular ejection fraction; coronary angiography and OCT were performed to define the lesion length, diameter stenosis degree of the infarct-related arteries, presence or absence of complex lesions, culprit lesion type, area stenosis degree and vulnerability of culprit plaques. Multivariable logistic regression analysis was performed to identify independent correlation factors. The receiver operating characteristic (ROC) curve of continuous independent correlation factors was analyzed, and the best cut-off value of TIMI 0-1 was respectively determined according to the maximum value of Youden index. Results: The mean age of 1 268 STEMI patients were (57.6±11.4) years old and 923 cases were males (72.8%). Compared with TIMI 2-3 group, the patients in TIMI 0-1 group were older and had higher N-terminal-pro-B-type natriuretic peptide level, lower cardiac troponin I (cTnI) level, lower left ventricular ejection fraction, and higher hsCRP level (5.16(2.06, 11.78) mg/L vs. 3.73(1.51, 10.46) mg/L). Moreover, the hsCRP level of patients in TIMI 0-1 group was higher in the plaque rupture subgroup (all P<0.05). Coronary angiography results showed that compared with TIMI 2-3 group, the proportion of right coronary artery (RCA) as the infarct-related artery was higher, the angiographical lesion length was longer, minimal lumen diameter was smaller, and diameter stenosis was larger in TIMI 0-1 group (all P<0.05). The prevalence of plaque rupture was higher (75.8% vs. 61.2%) in TIMI 0-1 group. Plaque vulnerability was significantly higher in TIMI 0-1 group than that in TIMI 2-3 group with larger mean lipid arc (241.27°±46.78° vs. 228.30°±46.32°), more thin-cap fibroatheroma (TCFA, 72.4% vs. 57.9%), more frequent appearance of macrophage accumulation (84.4% vs. 70.7%) and cholesterol crystals (39.1% vs. 25.7%). Minimal flow area was smaller [1.3(1.1-1.7)mm² vs. 1.4(1.1-1.9)mm², all P<0.05] and flow area stenosis was higher (78.2%±10.6% vs. 76.3%±12.3%) in TIMI 0-1 group. Multivariable analysis showed that mean lipid arc>255.55°, cholesterol crystals, angiographical lesion length>16.14 mm, and hsCRP>3.29 mg/L were the independent correlation factors of reduced preprocedural TIMI flow grade in STEMI patients. Conclusions: Plaque vulnerability and inflammation are closely related to reduced preprocedural TIMI flow grade in STEMI patients.
Aged ; Coronary Angiography ; Humans ; Inflammation ; Male ; Middle Aged ; Myocardial Infarction/diagnostic imaging* ; Percutaneous Coronary Intervention ; Plaque, Atherosclerotic/diagnostic imaging* ; Retrospective Studies ; ST Elevation Myocardial Infarction/surgery* ; Stroke Volume ; Thrombolytic Therapy ; Ventricular Function, Left

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.
Blood Pressure ; Chronic Disease ; Female ; Heart Rate ; Humans ; Hypertension ; Male ; Middle Aged ; Pedigree

Objective To explore the fire prevention management to ensure the operating of the data room in the hospital. Methods The hidden risks in the fire prevention of the data room were pointed out in auto fire fighting system,precision air-conditioning equipment, UPS and battery pack, compatibilization and expansion, high-voltage power supply circuit, lightningproof grounding and etc.It's indicated that the maintenance staff had deficiency in mastering related knowledge on gas fire-extinguishing system.Results The maintenance had to be strengthened for the auto fire fighting system,precision air-conditioning equipment,UPS and battery pack,and the detection should be reinforced for the high-voltage power supply circuit and lightningproof grounding system. It's suggested that standardized construction be executed during data room compatibilization and expansion,corresponding management system be established,and the knowledge be mastered on the composition,operation and announcements.Conclusion The fire prevention management of the data room is enhanced in the hospital,and the hidden risks are eliminated for fire fighting.

Objective To investigate the role of insular cortex in amygdala-kindled seizures in rats.Methods Forty-eight healthy male SD rats were randomly divided into blank control group (n=8),sham-operated group (n=8) and amygdala-kindled group (n=32); no treatment was performed in the blank control group,and only implantation of electrodes was performed in the sham-operated group; implantation of electrodes and electrophotoluminescence were performed in the amygdala-kindled group to induce amygdala-kindled seizure models.Rats in the amygdala-kindled group was divided into 4sub-groups (n=8) at different times after the kindling (1,3,6 and 12 h).Fluorescence in situ hybridization and immunohistochemistry staining were employed to investigate the altered mRNA and protein expressions of activity-regulated cytoskeleton-associated protein (Arc) in the hippocampus and insula of the rat brain.Results As compared with that in the blank control group and sham-operated group,Arc mRNA expression in the amygdala-kindled sub-groups increased at 1 h after the kindling (P＜0.05),peaked at 3 h after the kindling (P＜0.05),and returned to basic level at 6 h after the kindling (P＞0.05).As compared with that in the blank control group and sham-operated group,Arc protein expression in the amygdala-kindled sub-groups increased at 3 h after the kindling,(P＜0.05),peaked at 6 h after the kindling (P＜0.05),and returned to basic level at 12 h after the kindling (P＞0.05).No significant difference on mRNA and protein expressions of Arc was noted between the sham-operated group and blank control group (P＞0.05).Conclusion Insular cortex,the amygdala and the hippocampus form a focus complex,which participates in the occurrence of temporal lobe epilepsy.

OBJECTIVETo study the immunoregulation effects of Tiaomian No. 3 (TM3) for recurrent spontaneous abortion (RSA) caused by shortage of blocking antibodies.

METHODSTotally 61 patients with RSA caused by shortage of blocking antibodies were randomly assigned to the treatment group (31 cases) and the control group (30 cases) by lot method. Patients in the treatment group were treated with TM3, while those in the control group were treated with active immunotherapy using lymphocytes of their spouses. The therapeutic course for all was 3 months. Another 10 healthy females in the same age ranges were recruited as the healthy control group. The blocking antibodies (Ab1), anti-idiotypic antibodies (Ab2), T-lymphocyte cell subsets (CD4 and CD8), serum interleukin 10 (IL-10), and macrophage colony-stimulating factor (M-CSF) levels were determined before and after treatment.

RESULTS(1) After treatment the positive conversion rate of Ab1 and/or Ab2 was 87.1% (27/31) in the treatment group and 86.7% (26/30) in the control group, showing no statistical difference (P > 0.05). (2) In the two groups, CD4 decreased and CD8 increased. The CD4/CD8 ratio was in the normal level after treatment, showing statistical difference when compared with before treatment (P < 0.05). (3) In the two groups, IL-10 and M-CSF levels were higher after treatment, showing statistical difference when compared with before treatment (P < 0.05). (4) The 1-year conception rate was 58.1% (18/31) in the treatment group, significantly higher than that in the control group (46.7%, 14/30, P < 0.05).

CONCLUSIONSTM3 could promote the positive conversion rate of Ab1, promote the production of IL-10 and M-CSF cytokines, thus strengthening the protection for fetus by the mother and the normal maintenance for pregnancy. The 1-year successful pregnancy rate obviously increased in the treatment group.

Abortion, Habitual ; drug therapy ; immunology ; Adult ; Antibodies, Anti-Idiotypic ; Antibodies, Blocking ; CD4-CD8 Ratio ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Immunotherapy, Active ; Interleukin-10 ; blood ; Macrophage Colony-Stimulating Factor ; blood ; Phytotherapy ; Pregnancy ; T-Lymphocyte Subsets

OBJECTIVETo observe serum TGF-beta1 and TNF-alpha in silicosis patients and workers exposed to silica dust to study the role of TGF-beta1 and TNF-alpha in the development of silicosis.

METHODSOne hundred non-exposed workers were selected as control group, 200 workers exposed to silica dust for more than 1 year as exposed group, 32 suspected silicosis patients (originally diagnosed as 0+) as observing group, 130 silicosis patients were as silicosis group. Serum TGF-beta1 and TNF-alpha in each group were determined with ELISA.

RESULTSSerum TNF-alpha in exposed group [(47.86 +/- 16.52) pg/ml], observing group [(109.11 +/- 31.08) pg/ml], silicosis group [(216.35 +/- 51.03) pg/ml] were significantly higher than that in control group [(6.90 +/- 2.24) pg/ml] (P < 0.01); Silicosis group and observing group were also higher than exposed group (P < 0.01, P < 0.05). Compared with control group [(23.28 +/- 12.24) pg/ml] and exposed group [(29.31 +/- 14.52) pg/ml], serum TGF-beta1 in silicosis group was much higher (P < 0.01).

CONCLUSIONTGF-beta1, and TNF-alpha were essential in the development of silicosis, so the detection of TGF-beta1 and TNF-alpha in peripheral blood was very useful for occupational health surveillance and early diagnosis of silicosis.

Adult ; Case-Control Studies ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Silicosis ; blood ; diagnosis ; Transforming Growth Factor beta1 ; blood ; Tumor Necrosis Factor-alpha ; blood