Objective:To analyze the clinical phenotype and gene mutation of a genetic coagulation factor Ⅻ(FⅫ)deficiency pedigree and explore the molecular pathogenesis.Methods:The activated partial thromboplastin time(APTT)and FⅫ activity(FⅫ:C)were detected by clotting method.The FⅫ antigen(FⅫ:Ag)was tested with ELISA.All exons and flanks of F12 gene were determined by Sanger sequencing.ClustalX-2.1-win,PROVEAN and Swiss-Pdb Viewer software were used to analyze the conservatism of amino acids at the mutant site,forecast whether the mutant amino acids were harmful and confirm the influence of the mutation on protein structure.Results:The APTT of the proband prolonged to 71.3 s.The FⅫ:C and FⅫ;Ag were decreased to 5％and 6％,respectively.There were two heterozygous missense mutations c.580G＞T and c.1681G＞A detected in exon 7 and exon 14 of F12 gene,resultingin p.Gly175Cys and p.Gly542Ser,severally.Proband's father carried the p.Gly175Cys heterozygous mutation,while mother,brother and daughter had the p.Gly542Ser heterozygous mutation.Software analysis showed that both Gly175 and Gly542 were conserved,the two mutations were harmful and when mutations had occurred,the corresponding sites affected the protein local structure.Conclusion:The p.Gly175Cys and p.Gly542Ser compound heterozygous mutations are the molecular pathogenesis of the hereditary coagulation FⅫ deficiency pedigree.The p.Gly175Cys mutation has been detected for the first time in the world.

OBJECTIVES: To study the role and mechanism of autophagy in lipopolysaccharide (LPS)-induced inflammatory response of human alveolar epithelial A549 cells. METHODS: A549 cells were stimulated with LPS to establish a cell model of inflammatory response, and were then grouped (n=3 each) by concentration (0, 1, 5, and 10 μg/mL) and time (0, 4, 8, 12, and 24 hours). The A549 cells were treated with autophagy inhibitor 3-methyladenine (3-MA) to be divided into four groups (n=3 each): control, LPS, 3-MA, and 3-MA+LPS. The A549 cells were treated with autophagy agonist rapamycin (RAPA) to be divided into four groups (n=3 each): control, LPS, RAPA, and RAPA+LPS. The A549 cells were transfected with the Toll-like receptor 4 (TLR4) overexpression plasmid to be divided into four groups (n=3 each): TLR4 overexpression control, TLR4 overexpression, TLR4 overexpression control+LPS, and TLR4 overexpression+LPS. The A549 cells were transfected with TLR4 siRNA to be divided into four groups (n=3 each): TLR4 silencing control,TLR4 silencing, TLR4 silencing control+LPS, and TLR4 silencing+LPS. CCK-8 assay was used to measure cell viability. Western blot was used to measure the protein expression levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4. RESULTS: After stimulation with 1 μg/mL LPS for 12 hours, the levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4 increased and reached the peak (P<0.05). Compared with the LPS group, the 3-MA+LPS group had reduced expression of autophagy-related proteins and increased expression of inflammation-related proteins and TLR4, while the RAPA+LPS group had increased expression of autophagy-related proteins and reduced inflammation-related proteins and TLR4 (P<0.05). The TLR4 overexpression+LPS group had reduced autophagy-related proteins and increased inflammation-related proteins compared with the TLR4 overexpression control+LPS group, and the TLR4 silencing+LPS group had increased autophagy-related proteins and reduced inflammation-related proteins compared with the TLR4 silencing control+LPS group (P<0.05). CONCLUSIONS In the LPS-induced inflammatory response of human alveolar epithelial A549 cells, autophagic flux has a certain protective effect on A549 cells. TLR4-mediated autophagic flux negatively regulates the LPS-induced inflammatory response of A549 cells.
Humans ; A549 Cells ; Autophagy ; Beclin-1/metabolism* ; Caspase 1/metabolism* ; Inflammation ; Lipopolysaccharides/pharmacology* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Toll-Like Receptor 4/metabolism*

Aim To investigate the effect of CPD1 , a novel phosphodiesterase 5 inhibitor, on contractile ten- sion of pulmonary artery and aorta in rats with pulmonary arterial hypertension ( PAH ) .Methods MCT- induced PAH was generated by a single intraperitoneal injection of MCT(50 mg • kg"1) in rats.Seven days after MCT injection, the rats were treated with CPD1 ( 10 mg • kg-1 • d"1) for 14 days.The tension of vascular rings was examined in MCT-induced PAH rats.Results MCT treated rats exhibited profound PAH when examined 3 weeks after injection.In contrast, gavage administration of CPD1 led to significant decrease in the right ventricle systolic pressure ( RVSP) and right ventricular mass index (RVMI), as well as MCT-induced pulmonary arterial wall thinning and enlarged lumen, indicating that CPD1 inhibited the de- velopment of PAH.Cavage administration of CPD1 also reduced phenylephrine and endothelin-1-induced pulmonary artery contraction and aorta contraction in MCT-treated rats.Conclusions Treatment with CPD1 attenuates vascular reactivity, lessens vascular smooth muscle cell proliferation and remodeling, and inhibits PAH via inhibition of non-voltage dependent Ca2∗ channels in normal and PAH rats.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

As an important signal molecule, extracellular ATP(eATP) can regulate many physiological and biochemical responses to plant stress. In this study, the regulation of extracellular ATP(eATP) on chlorophyll content and chlorophyll fluorescence parameters of Angelica sinensis seedlings were studied under drought and low temperature stress. The results showed that all the chlorophyll content, the actual photochemical efficiency [Y(Ⅱ)], the electron transfer rate(ETR), the photochemical quenching coefficient(qP and qL) of A. sinensis leaves were significantly decreased under drought and low temperature stress, respectively. At the same time, non-photochemical quenching(NPQ and qN) were also all significantly increased, respectively. The application of eATP alleviated the decrease of chlorophyll content, Y(Ⅱ), ETR, qP and qL of A. sinensis leaves under drought and low temperature stress, and eliminated the increase of qN and NPQ. The results indicated that eATP could effectively increase the open ratio of PSⅡ reaction centers, and improve the electron transfer rate and light energy conversion efficiency of PSⅡ of A. sinensis leaves under drought and low temperature stress. It is beneficial to enhance the chlorophyll synthesis and the adaptability of PSⅡ about A. sinensis seedlings to drought and low temperature stress.
Adenosine Triphosphate ; pharmacology ; Angelica sinensis ; chemistry ; physiology ; Chlorophyll ; analysis ; Cold Temperature ; Droughts ; Fluorescence ; Photosynthesis ; Plant Leaves ; chemistry ; Seedlings ; chemistry ; physiology ; Stress, Physiological ; Water

Objective To understand the relationship between the concentration of air pollutants and daily emergency department visits for different diseases (circulatory system disease, digestive system disease, nervous system disease and respiratory system disease) in Guangzhou, Guangdong Province. Methods The daily average concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2, carbon monoxide (CO) and PM2.5 and the daily maximum 8-hour concentrations of O3, the daily average temperature, the relative humidity and cause -specific emergency department visits of the four major diseases from 2015 to 2017 were collected in Guangzhou. Semi-parametric generalized additive model was used to analyze the relationship between the concentration of pollutants and daily cause-specific emergency department visits. Results The daily average concentrations of SO2, NO2, CO, O3 and PM2.5 during the study period were 13.24 μg /m3, 45.96 μg /m3, 0.97 mg /m3, 123.77 μg /m3 and 36.22 μg /m3, respectively. For circulatory system disease，the independently significant associations of SO2 with emergency department visits in single-pollutant models (2.91%, 95% CI: 1.00%-4.85%), and multipollutant models (4.39%, 95% CI: 1.22%-7.67%) were observed. Conclusion The ambient SO2 increases the risk of emergency department visits due to circulatory diseases in Guangzhou. Comprehensive prevention and control measures should be taken to reduce the emission of SO2.

Objective To compare the early clinical efficacy of unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) for elderly patients with medial compartmental knee osteoarthritis.Methods A total of 35 elderly patients with medial compartmental knee osteoarthritis were selected from September 2014 to March 2018 in our hospital, of whom 16 cases treated by UKA were observation group and 19 cases treated by TKA were control group.ResultsThe operation time, intraoperative blood loss, the rate of perioperative blood transfusion, postoperative drainage volume and hospitalization stays of observation group were less than those of control group, the difference were significant (P＜0.05).Before the treatment, there was no significant differences in the KSS score between two groups (P＞0.05).After the treatment, KSS scores of two groups had been improved to some extent, and the observation group was better than the control group, the difference was significant (P＜0.05).No revision or infection happened in 1 year post-operative follow-up of either group.The observation group (0) were less than the control group (26.32％) in thrombosis rate, the difference was significantly (P＜0.05).ConclusionBoth UKA and TKA have certain early clinical efficacy, but UKA had advantages such as shorter operation time, shorter hospitalization, less pain, lower incidence of adverse reaction, which can promote the postoperative function recovery, the early clinical efficacy is more significant.

In this study we investigate the effects of cadmium stress on Astragalus membranaceus seedlings and the alleviative effects of attapulgite clay in growth substrate on cadmium stress to A. membranaceus seedlings. The results showed that the Y (Ⅱ) (effective photochemical quantum yield of PSⅡ photosynthetic), qP(photochemical quenching coefficient), ETR(the rate of non-cyclic electrontransport through PSⅡ), and chlorophyll content of the leaves were significantly decreased with the increase of cadmium concentrations, while the cadmium content, non-photochemical quenching(NPQ, qN) of the leaves and cadmium content, MDA content, plasma membrane permeability, and the damage degree of root apical membrane of the roots were significantly increased. Simultaneously, the activities of APX(ascorbate peroxidase), SOD(superoxide dismutase), POD(peroxidase), CAT(catalase), soluble protein content, and soluble sugar content of roots were increased first but then decreased with the increasing cadmium concentration. Under the condition of without Cd stress, the attapulgite clay into the growth substrate did not significantly affect above physiological indexes of leaves, but significantly increased SOD activity and soluble sugar content of roots and decreased the MDA content, damage degree of root apical membrane of roots, while other physiological indexes did not significantly change. Under cadmium stress, the presence of attapulgite clay in the growth substrate significantly alleviated the cadmium-induced decreases Y (Ⅱ), qP, ETR and chlorophyll content of leaves, and the CAT activity, soluble protein content, and soluble sugar content of roots. Under condition with cadmium stress, the presence of attapulgite clay significantly alleviated the cadmium-induced increases of leaves cadmium content, qN and NPQ, and the cadmium content, MDA content, plasma membrane permeability, damage degree of root apical membrane, SOD, POD, and APX activity of the roots. And, the alleviative effects of attapulgite clay on cadmium stress to A. membranaceus roots were more obvious with the increase of cadmium stress time. The above results showed that the addition of attapulgite clay into the growth substrate has certain alleviative effect on the cadmium stress to A. membranaceus seedlings.

BACKGROUNDGlobally, the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.

METHODSAll the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed.

RESULTSA total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents' concern about the long-term outcomes was the main reason of medical care withdrawal.

CONCLUSIONSNeonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.

Cause of Death ; China ; Female ; Hospital Mortality ; Humans ; Infant ; Infant Mortality ; Infant, Newborn ; Infant, Newborn, Diseases ; mortality ; Intensive Care Units, Neonatal ; statistics & numerical data ; Male ; Perinatal Death ; Retrospective Studies