BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant hereditary disease. Its early diagnosis and intervention significantly improve the patient's quality of life. However, there are few types of research on the FH pathogenic genes in China. METHODS: In this study, we recruited a family diagnosed with FH and used whole exome sequencing (WES) to analyze the proband variants. Intracellular cholesterol level, reactive oxygen species (ROS) level, and the expression of pyroptosis-related genes were detected after overexpression of wild-type or variant LDLR in L02 cells. RESULTS: A heterozygous missense variant predicted to be deleterious to LDLR (c.1879G > A, p.Ala627Thr) was identified in the proband. Mechanistically, intracellular cholesterol level, ROS level, and the expression of pyroptosis-related genes, nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3), gasdermin D (GSDMD), interleukin (IL) -18, IL-1β was elevated in the variant LDLR group, which was attenuated by inhibition of ROS. CONCLUSIONS FH is associated with a variant (c.1879G>A, p.Ala627Thr) in the LDLR gene. Regarding the mechanism, the ROS/NLRP3-mediated pyroptosis in hepatic cells may contribute to the pathogenesis of the LDLR variant.

Objective To understand the characteristics and developmental differences between cerebral organoids in vitro and normal cerebral cortices in vivo. Methods 1. Grouping: cerebral cortices in vivo group and cultured cerebral organoids in vitro group. 2. Sample collection: cortical tissues were collected from Kunming mouse embryos at embryonic day 7.5(E7.5), E9.5, E11.5, E14.5, and postnatal day 3 (P3) or P7. Three specimens were taken from each group. Meanwhile, cerebral organoids were cultured with mouse induced pluripotent stem cells (iPSCs), and samples at different culture time point were collected, and more than 3 samples were collected at each time point. 3. Detection method: the distribution of different types of cells in each group of specimens was analyzed by immunofluorescent staining. Results While relative similarities between in vivo cerebral cortical development and the cerebral organoids in vitro were observed, including the histogenesis, and the morphological differentiation of nerve cells and glial cells, the lamellar architecture of cerebral cortex in mouse brain was not observed in cerebral organoids. Conclusion The development of cerebral organoids in vitro has some similarity with body's cortical development. Therefore, cerebral organoids can be used to a substitution of cortex and diseases' models, but improvement of the existing technologies is necessary.

Objective:To investigate the epidemiological and clinical characteristics of human parainfluenza viruses (HPIVs) infection among hospitalized children with community-acquired pneumonia (CAP) in China, and provide basic data for diagnosis, treatment and prevention of HPIVs infection.Methods:From November 2014 to February 2020, 5 448 hospitalized children with CAP were enrolled in 14 hospitals in 11 provinces and municipalities directly under the Central Government in southern China and northern China. Nasopharyngeal aspirates or throat swabs were collected, and the nucleic acids of 18 types respiratory viruses including HPIV1-4 were screened by suspension array technology. Demographic data and clinical information were collected for statistical analysis.Results:The total detection rate of HPIVs in 5 448 children with CAP was 8.83% (481/5 448), and the detection rate in males was higher than that in females (62.79% vs. 37.21%; χ2=0.000, P=0.992). The detection rate of HPIVs in 1~< 3 years age group was higher than that in other age groups, and the difference was statistically significant ( χ2=61.893, P<0.001). The detection rate of HPIVs in the northern region was higher than that in the southern region (9.02% vs 8.65%), but the difference was not statistically significant ( χ2=0.239, P=0.625). The prevalence of HPIV1-4 in northern and southern China was not completely same. HPIV1 was mainly prevalent in autumn in both northern and southern regions. HPIV2 was prevalent in summer in northern China, and the detection rate was low in southern China. HPIV3 reached its peak in both spring and summer in both northern and southern China, but its duration was longer in southern China than in northern China. HPIV4 is mainly popular in autumn in both southern China and northern China. Among 481 children infected with HPIVs, 58.42% (281/481) were infected with HPIV alone, and the main clinical manifestations were cough (90.75%) and fever (68.68%). Out of the HPIV-positive cases, 42.62% (205/481) were co-infected with another type of HPIV or a different virus, while 11.43% (55/481) had co-infections with two or more different viruses. HPIV3 was the most common type of co-infection with other viruses. HPIV3 infection accounted for the largest proportion (76.80%) in 47 HPIVs-positive children with severe pneumonia. Conclusions:HPIVs is one of the most important pathogens causing CAP in children in China, and children under 3 years of age are the main populations of HPIVs infection. The prevalence characteristics of all types of HPIVs in children in the north and south are not completely same. HPIV3 is the dominant type of HPIV infections and causes more severe diseases.

Objective To investigate the effect of intravenous dexmedetomidine injection(1 μg/kg)on the intubating conditions after inhalation induction with sevoflurane 8% and nitrous oxide(NO)50% in children. Methods Totally 122 patients aged 4-10 years with an American Society of Anesthesiologists physical statusⅠ undergoing elective plastic surgery under general anesthesia were randomly divided to dexmedetomidine group(intraveneously injected with dexmedetomidine 1μg/kg)and control group(injected with normal saline)by using the random sampling table.On arrival of the operating room,anesthesia was induced with sevoflurane 8% and NO 50% in oxygen 50%.When the patient became unconscious,the intravenous cannula 24was inserted on the dorsum of hand.One minute later,laryngoscopy and tracheal intubation were performed.The intubating conditions were assessed by the scoring system in the previous study. Results The rates of acceptable conditions were 97% and 90% in dexmedetomidine group and in control group(P=0.143),and the rates of excellent conditions were 82% and 67%(P=0.04),respectively.In dexmedetomidine group,there were no signifi-cant differences of mean arterial presser and heart rate between the time-point of before intubation and the time-point of immediately after intubation.Conclusion Intravenous bolus of dexmedetomidine(1 μg/kg)can effectively improve the intubating conditions after inhalation induction of sevoflurane 8% and NO 50% in children and make the hemodynamics more stable during tracheal intubation.

Objective To observe the effects of two different intranasal dexmedetomidine doses as premedication on the ECof sevoflurane for successful laryngeal mask airway placement in children. Methods Children aged 3-6 years, of American Society of Anesthesiologists physical status 1, and scheduled for plastic surgery were enrolled in this study. Children were assigned to receive either spray administration of intranasal dexmedetomidine 1 μg/kg (group D1, n=21) or 2 μg/kg (group D2, n=20) approximately 30 minutes before anesthesia. Anesthesia was induced with sevoflurane up to 8% in 100% O, with fresh gas flow set to 6 L/min. After the pupil fixed to the middle position, sevoflurane dial setting was reduced to 5% and fresh gas flow reduced to 3 L/min. The endtidal sevofluran (ET) concentration for laryngeal mask airway insertion sustained for 10 minutes after vein intubation, which was determined according to the Dixon's up and down method. The initial endtidal sevoflurane concentration in each group was set at 2%. ETwas increased/decreased (1:1.2) in the next patient according to the response to laryngeal mask airway insertion. Bispectral index, mask acceptance, all response to laryngeal mask airway insertion, and ETof laryngeal mask airway insertion of children were recorded. Results The bispectral index value was 77.4±3.6 in group D2, which was significantly lower than that (87.4±1.9) in group D1 when children entered operation room (P<0.05). Mask acceptance was 76.2% in group D1 and 90.0% in group D2. The ECof sevoflurane for laryngeal mask airway insertion was 1.09% (95% CI=0.89%-1.28%) in group D2, which was lower than 1.59% (95% CI=1.41%-1.78%) in group D1 (P<0.05). Conclusion Compared with the dose of 1 μg/kg, spray administration of intranasal dexmedetomidine 2 μg/kg as premedication can reduce the sevoflurane ECfor successful laryngeal mask airway placement in children.
Administration, Intranasal ; Anesthesia ; Anesthetics, Inhalation ; administration & dosage ; Child ; Child, Preschool ; Dexmedetomidine ; administration & dosage ; Humans ; Laryngeal Masks ; Methyl Ethers ; administration & dosage

Objective To compare two spray administration of intranasal dexmedetomidine (DEX) doses for premedication in children. Methods In this prospective,randomized,double-blind study,41 children aged 3-6 years were enrolled. Children were assigned to receive either spray administration of intranasal DEX 1 μg/kg (Group D1) or 2 μg/kg (Group D2). The Ramsay Sedation Scale scores were evaluated at 5 min intervals. Sedation status at separation from patient was also evaluated. Heart rate (HR) and saturation of peripheral oxygen (SpO) were recorded before and every 15 min after drug administration. Results The median sedation onset time was 30 min and 20 min in group D1 and group D2,respectively. Compared with the children in group D1,those in group D2 were significantly more sedated when they were separated from their parents (61.9% vs. 95.0%,respectively)(χ=5.549,P=0.010). In Group D2,the HR decreased by 15.8% (t=2.415,P=0.021) 30 min after the spray administration of intranasal DEX. Compared with the baseline values,there was no significant difference in both groups in terms of SpO(t=-1.426,P=0.162;t=-1.096,P=0.280)and HR in group D1 (t=-0.299,P=0.767) 30 min after the spray administration of intranasal DEX. Conclusion Spray administration of intranasal DEX 2 μg/kg provides superior sedation in children.
Administration, Intranasal ; Anesthesia ; methods ; Child ; Child, Preschool ; Dexmedetomidine ; administration & dosage ; Double-Blind Method ; Female ; Heart Rate ; Humans ; Hypnotics and Sedatives ; administration & dosage ; Male ; Oxygen ; analysis ; Prospective Studies

OBJECTIVETo study the distribution and drug resistance of methicillin resistant Staphylococcus strains in various specimens of inpatients in burn wards, and to provide reference for clinical treatment.

METHODSBacteria were isolated from specimens of wound exudate, blood, sputum, and bronchoalveolar lavage fluid etc., which were collected from patients hospitalized in our burn wards from January 2008 to December 2010. The bacteria were routinely cultured and identified. Drug resistance of the Staphylococci to 15 antibiotics commonly used in clinic was identified by K-B disk diffusion method. Data were processed with statistical software WHONET 5.5. The homology of 40 strains of methicillin resistant Staphylococcus aureus (MRSA) was analyzed by pulsed-field gel electrophoresis (PFGE).

RESULTSAltogether 386 strains of Staphylococcus were isolated, including 196 strains of Staphylococcus aureus and 190 strains of coagulase negative Staphylococcus. The mean annual isolation rates of MRSA and methicillin resistant coagulase negative Staphylococcus (MRCoNS) were respectively 73.00% (143/196) and 74.20% (141/190). The resistance rates of MRSA and MRCoNS to β-lactams drugs, such as penicillin, oxacillin, cefazolin, and cefuroxime were 100.00% in every year. No Staphylococcus strains resistant to vancomycin, teicoplanin, or linezolid were found. Three different PFGE patterns A, B, and C were identified among 40 MRSA strains, including 33 strains of type A (30 strains in sub-type A1 and 3 strains in sub-type A2), 6 strains of type B (respectively 3 strains in sub-types B1 and B2), and 1 strain of type C.

CONCLUSIONSThe isolation rates of MRSA and MRCoNS were high in our burn wards from January 2008 to December 2010. All of them showed strong drug resistance property, and they were multidrug resistant. The most prevalent strain was PFGE type A.

BackgroundWith the increasing prevalence of dry eye and the continuous improvement of living standards,the problem of dry eye more and more get the attention of people.At present,China still lacks the large population-based epidemiological data of dry eye. Objective To investigate the prevalence and possible risk factors of dry eye in a community of Huidong County of population aged 14 and over.Methods From September 2010 to January 2011,using questionnaires and examination of dry eye related,2800 people were selected randomly for cross-sectional survey.Those suspected as dry eye were examed by the SchirmerⅠtest ( S Ⅱ T),tear-film breakup time(BUT),corneal fluorescein staining(F1).Results In the 2475 questionnaire effectively,154 persons were diagnosed as dry eye,and the prevalence rate of dry eye was 6.22％,8.06％in females,4.14％in males.The prevalence rate increases with age.The S Ⅰ T and BUT decreased with increasing age.S Ⅰ T and BUT in females are less than males.Foreign body sensation is the primary complaints of patients.Logistic analysis showed that the most common risk factors in dry eye are age and gender.The system disease and eye diseases,eye fatigue and long exposure to dust are also main determinants.ConclusionsThe population prevalence rate of dry eye increased with age,the prevalence rate of dry eye in females is higher than that in males.The key factors associated with dry eye are age,gender,systemic disease and eye diseases,occupation,working environment.

Objective To understand the changing trends of non-communicable diseases (NCDs) in Xinjiang Production and Construction Corps from 1998 to 2008.Methods A stratified-cluster random sampling based cross-sectional NCDs survey was carried out in 2008,and using the data of NCDs from the health service surveys in 1998 and 2004,in Xinjiang Production and Construction Corps.The prevalence rate of NCDs was standardization according to age proportion of the population being surveyed in 1998.Results In 1998,2004 and 2008,the prevalence rates of NCDs in Xinjiang Production and Construction Corps were 17.26%,25.61%,24.85% while the Standardized rates of NCDs were 17.26%,23.54% and 20.49% respectively.The prevalence rates of NCDs were statistically significant different in 35-,45-,55- and over 65 age groups in 1998,2004 and 2008 which showed an consecutive upward trend.The prevalence rates of hypertension,diabetes,cerebrovascular disease,coronary heart disease and chronic obstructive pulmonary disease increased significantly from 1998 to 2008.The prevalence rate of hypertensive disease among 25- age group,diabetes among 35- age group,cerebrovascular disease and coronary heart disease among 45- age groups showed an increasing trend.Conclusion Cardiovascular and cerebrovaseular diseases,together with diabetes were the fastest increasing ones over the past 10 years and becoming the major diseases,making the Xinjiang Production and Construction Corps an aging population.NCDs should be prioritized in the health development plan.Targeted health education should be carried out in the whole population,together with other interventions as well as management programs on chronic diseases to reduce the prevalence of NCDs.

Objective To explore the feasibility of detecting atherosclerosis with 7.0T MR and Micro-PET. Methods Ten 46-week-old ApoE-/- mice with high lipid diet for 6 months were selected to establish atherosclerosis models. Among them, 5 mice underwent MRI before and 12 h, 24 h, 36 h after injection of SPIO, respectively, and the other 5 mice were injected with ~(18)F-fluorodeoxyglucose (~(18)F-FDG) through tail vein and observed with Micro-PET after 1 h, 2 h and 3 h. The specimens of abdominal aorta were taken for pathologic examination. Results Atherosclerotic plaques were observed in all animals with 7.0T MRI after 6 months high lipid diet. Thirty-six hours after the injection of SPIO, the high signal rings were thinner and the lumen of blood vessels were wider than those before injection on T2WI. Radioactive concentration was observed in abdominal aorta and both sides of iliac artery 3 h after the injection of ~(18)F-fluorodeoxyglucose (~(18)F-FDG). Pathological examination showed the formation of atherosclerotic plaques and the aggregation of the macrophages. Conclusion 7.0T MRI and Micro-PET can be used to observe the macrophage-rich plaque and to judge the vulnerability of plaque, thus provide theoretical basis for early detection, diagnosis and treatment of atherosclerosis.