Squalene epoxidase (SQLE) is a potential target for the treatment of liver cancer. Bioinformatics analysis indicated that the high expression of SQLE was closely related to the clinical stage and poor prognosis of patients with liver cancer. However, the existing inhibitors against SQLE 195 tyrosine residue (Y195) cannot be used clinically due to severe side effects. In this study, 35 small-molecule compounds targeting SQLE 335 tyrosine residue (Y335) were selected by computer virtual screening. Combined with MTT assay, 3 candidate compounds (19^#, 31^# and 35^#) with significant inhibitory effects on the proliferation of Huh7 cell line were obtained. Further studies showed that these 3 compounds could inhibit the migration of Huh7 cells, reduce the contents of total and free cholesterol, up-regulate the expression of tumor suppressor gene PTEN, and down-regulate the expression of PI3K and AKT proteins. The results showed that the novel inhibitors 19^#, 31^# and 35^# targeting SQLE Y335 could reduce cholesterol content, inhibit the proliferation and migration of Huh7, thus playing an anti-liver cancer role.

Humans ; Fibrosarcoma/surgery* ; Sarcoma ; Temporal Bone ; Soft Tissue Neoplasms/surgery*

To investigate the common specific immunoglobulin E(sIgE) in children with eczema and urticaria, compare the allergies in children with different diseases, genders and ages, and provide the scientific basis for the prevention, diagnosis and treatment. A retrospective study was conducted to analyze the children who were suspected of eczema and urticaria and tested for serum sIgE in the Tianjin Children's Hospital from December 2019 to August 2021. A total of 8 092 serum samples were tested for ten food allergens and ten inhaled allergens. The method was the enzyme-linked immune capture assay. The allergen epidemiological characteristics were statistically analyzed by Chi square test based on the children's characteristics and factors such as different sexes and ages and by the mass data. The results showed that the positive rate of eczema was 64.42%(5 213/8 092), and the urticaria was 35.58%(2 879/8 092). The positive rate of specific IgE was 66.65%(5 393/8 092), the food allergens was 61.74%(4 996/8 092), and the inhaled allergens was 34.85%(2 820/8 092). The top three positive rates of food allergens were egg 46.65%(3 775/8 092), milk 32.64%(2 641/8 092) and wheat flour 15.08%(1 220/8 092). The top three positive rates of inhaled allergens were house dust 21.40%(1 732/8 092), Alternaria 11.78%(953/8 092) and Dermatophagoides farinae 7.33%(593/8 092). The positivity of food allergens and inhaled allergens was significantly different in different age groups. The positive rates of food allergens in different age groups were 48.92%(947/1 936) in<1 year old, 72.28%(2 680/3 708) in 1-3 years old, 64.58%(919/1 423) in 4-6 years old and 43.90%(450/1 025) in>6 years old. The positive rates of inhaled allergens in different age groups were 17.67%(342/1 936) in<1 year old, 36.35%(1 348/3 708) in 1-3 years old, 46.38%(660/1 423) in 4-6 years old and 45.85%(470/1 025) in>6 years old. The top six positive rates of allergens of eczema were the same with urticaria, which were egg, milk, house dust, wheat flour, Alternaria and Dermatophagoides farinae. The allergens (greater than or equal to grade 4) differed in children with eczema and urticaria. Moreover, there were significant differences in the positive rates of Alternaria, egg, wheat flour, crab and shrimp. In conclusion, this study can reflect the epidemic characteristics of allergens in children with eczema and urticaria to a certain extent. There were significant differences in the positive rates of allergens between different age groups. It is necessary to reasonably avoid the high-risk allergens according to the epidemiological characteristics and clinical symptoms, which provide valuable information for the prevention, diagnosis and treatment of allergic diseases.
Infant ; Child ; Humans ; Female ; Male ; Child, Preschool ; Flour ; Retrospective Studies ; Triticum ; Urticaria/epidemiology* ; Eczema/epidemiology* ; Hospitals ; Immunoglobulin E ; Allergens ; Dust

To investigate the common specific immunoglobulin E(sIgE) in children with eczema and urticaria, compare the allergies in children with different diseases, genders and ages, and provide the scientific basis for the prevention, diagnosis and treatment. A retrospective study was conducted to analyze the children who were suspected of eczema and urticaria and tested for serum sIgE in the Tianjin Children's Hospital from December 2019 to August 2021. A total of 8 092 serum samples were tested for ten food allergens and ten inhaled allergens. The method was the enzyme-linked immune capture assay. The allergen epidemiological characteristics were statistically analyzed by Chi square test based on the children's characteristics and factors such as different sexes and ages and by the mass data. The results showed that the positive rate of eczema was 64.42%(5 213/8 092), and the urticaria was 35.58%(2 879/8 092). The positive rate of specific IgE was 66.65%(5 393/8 092), the food allergens was 61.74%(4 996/8 092), and the inhaled allergens was 34.85%(2 820/8 092). The top three positive rates of food allergens were egg 46.65%(3 775/8 092), milk 32.64%(2 641/8 092) and wheat flour 15.08%(1 220/8 092). The top three positive rates of inhaled allergens were house dust 21.40%(1 732/8 092), Alternaria 11.78%(953/8 092) and Dermatophagoides farinae 7.33%(593/8 092). The positivity of food allergens and inhaled allergens was significantly different in different age groups. The positive rates of food allergens in different age groups were 48.92%(947/1 936) in<1 year old, 72.28%(2 680/3 708) in 1-3 years old, 64.58%(919/1 423) in 4-6 years old and 43.90%(450/1 025) in>6 years old. The positive rates of inhaled allergens in different age groups were 17.67%(342/1 936) in<1 year old, 36.35%(1 348/3 708) in 1-3 years old, 46.38%(660/1 423) in 4-6 years old and 45.85%(470/1 025) in>6 years old. The top six positive rates of allergens of eczema were the same with urticaria, which were egg, milk, house dust, wheat flour, Alternaria and Dermatophagoides farinae. The allergens (greater than or equal to grade 4) differed in children with eczema and urticaria. Moreover, there were significant differences in the positive rates of Alternaria, egg, wheat flour, crab and shrimp. In conclusion, this study can reflect the epidemic characteristics of allergens in children with eczema and urticaria to a certain extent. There were significant differences in the positive rates of allergens between different age groups. It is necessary to reasonably avoid the high-risk allergens according to the epidemiological characteristics and clinical symptoms, which provide valuable information for the prevention, diagnosis and treatment of allergic diseases.
Infant ; Child ; Humans ; Female ; Male ; Child, Preschool ; Flour ; Retrospective Studies ; Triticum ; Urticaria/epidemiology* ; Eczema/epidemiology* ; Hospitals ; Immunoglobulin E ; Allergens ; Dust

Animals ; Genomics ; Humans ; Serogroup ; Streptococcal Infections ; Streptococcus suis/isolation & purification* ; Swine ; Swine Diseases

Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.

OBJECTIVE: To observe the safety of donor NK cell infusions in the settings of hematopoietic stem cell transplantation and after consolidation chemotherapy in elderly patients with acute myeloid leukemia (AML). METHODS: Forty patients with AML were included, in which 21 patients aged over 60 years were at the stage of complete remission (CR) and 19 patients that received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mononucleated cells were isolated from peripheral blood from the donors (for allo-HSCT) or healthy immediate family members (elderly AML). The cells were seeded into the flasks pre-coated with NK cell specific activators, and expanded in media containing recombinant human IL-15 and IL-2 for 14 days. The cells were transfused intravenously after the identification of quality control. Trypan blue exclusion test was used for the determination of cell viability and counting. Flow cytometry analysis was performed to assess the surface antigenic profile. Seventy-eight infusions of the cell products were received by the elderly patients with AML after consolidation chemotherapy, 11 infusions were received by the patients during allo-HSCT and 32 infusions 3 moths after transplantation. The safety of cell therapy, body temperature, blood pressure and other indexes were observe during and 48 hours after cell transfusion. Meanwhile, the occurrence and severity of acute graft-versus-host disease (GVHD) were documented. RESULTS: Flow cytometry analysis showed that the proportion of NK cells (CD3^-CD56⁺) in the mononucleated cells before culture was (14.10±4.22)% (n=121), and the proportion increased dramatically up to (87.29±8.75)% (n=121) after culture for 14 days, the number of NK cells increased to 753.47±140.13 times (n=121). The doses of the infused NK cells was (7.58±2.50)×10⁷/kg per infusion. Moderate fever occurred in three cases after multiple infusions, and the temperature restored to normal on the same day after treatment. Fever was observed in one patient after every infusion of four times in total. The temperature reached to 38.5-39.0 ℃ and returned to normal within 1-2 hours after adequate antipyretic treatment, and then there was no discomfort. No GVHD was observed in the elderly AML patients, while 6 cases that received allo-HSCT developed moderate acute GVHD, among them grade I in 5 cases and grade II in 1 case. No other severe toxicities were observed. CONCLUSION NK cell products with a high-purity could be obtained by ex vivo expansion with this protocol. The transfusion of these expanded cells is generally safe in the elderly patients with AML that have received chemotherapy or patients that received hematopoietic stem cell transplantation.
Aged ; Graft vs Host Disease/prevention & control* ; Hematopoietic Stem Cell Transplantation ; Humans ; Killer Cells, Natural ; Leukemia, Myeloid, Acute/therapy* ; Middle Aged ; Recurrence

Objective:To explore the effect of systolic anterior motion (SAM) of mitral valves on the morphology and function of left ventricular outflow tract (LVOT) in patients with hypertrophic obstructive cardiomyopathy (HOCM) using computer fluid dynamics based on three-dimensional echocardiography with inverted grey values.Methods:A total of 40 patients with hypertrophic cardiomyopathy were divided into SAM group (24 cases) and non SAM group (16 cases) in Renmin Hospital of Wuhan University from April 2016 to October 2019. Two dimensional and three-dimensional echocardiographic data of the patients were collected. The LVOT morphological model was constructed based on the post-processing of three-dimensional echocardiography data, and the LVOT flow field model was constructed based on the time-volume curve of left ventricle. LVOT peak velocity was obtained to assess the agreement with echocardiography measurements. Area of LVOT, average velocity, flow rate and iso-surface area of vortex of different levels were obtained and compared between the two groups.Results:There was a good correlation between cardiac fluid model and echocardiographic measurement ( r=0.943, P<0.01). The Bland-Altman consistency interval was -75.0-111.3, and 92.5% of the points were within the consistency limit. Compared with non-SAM group patients, the peak velocity of LVOT increased, the area of LVOT decreased, the flow rate decreased and the area of vortex increased in SAM patients (all P<0.01). In the SAM group, in 16 patients the double orifice LVOT was observed due to the contact between mitral valve and septum, in 1 patient the single orifice LVOT structure was observed with contact between mitral value and septum, and in 7 patients, single orifice LVOT without contact between mitral value and septum. In SAM patients, compared with single orifice LVOT, patients with double orifice LVOT were observed with higher LVOT velocity, smaller LVOT area and higher vortex area with high level(all P<0.05). Conclusions:Accurate fluid models can be obtained using three-dimensional echocardiography with inverted grey values. In SAM patients, contact between mitral valve and septum leads to the formation of double orifice structure and the increase of vortex level in LVOT.

Objective To explore the theories, content and approaches of integrating physical activity in children's eye health service system in the context of health services. Methods From the perspectives of six building blocks of WHO health system, namely, leadership and governance, financing, human resources for health, service delivery, medical technology, and health information system, we analyzed the policy framework and key contents related to school-based eye health and physical activity, and explored how to promote the implementation of physical activity into the school-based eye health service system, and the integration of physical activity into the eye health continuum: prevention, intervention, rehabilitation, and health promotion. Results In perspective of health system, the integration of physical activity into school-based eye health services should be in accordance with the five principles of cross-cutting health services, namely, universal accessibility and equity, human rights, evidence-based, life-span, and empowerment. According to the World Vision Report, WHO advocates to build a person-centered eye health service system, and person-centeredness is the core concept of the new model of school-based eye health services and physical activity integration. WHO advocates a school-based approach to education and physical activity in health-promoting schools to promote student health, physical activity as a preventive, interventional, rehabilitation and health promotive measure related to children's eye health, and vigorously train professionals within schools who have knowledge and skills related to physical activity and eye health, build an information system on physical activity and children's eye health, and promote the integration of physical activity into the school-based eye health service system. Conclusion Physical activity is an important measure to promote children's eye health and an important component to achieve a person-centered eye health service system. Based on the six building blocks of the WHO health service system, a school-based eye health service that integrates a theoretical and methodological system of physical activity is constructed, requiring the provision of health promotion methods such as education and physical activity in the school setting, to enhance leadership and governance of eye health services based on educational and physical activity approaches in the school setting, establish new funding mechanisms, provide financial security, develop human resources related to physical activity for eye health, improve related service delivery systems, develop high-quality physical activity intervention eye health techniques and equipment, and integrate information on children's physical activity and eye health into school health information systems to achieve children's eye health and promote their physical and mental development.

Caffeic acid and its oligomers are the main water-soluble active constituents of the traditional Chinese medicine(TCM) Arnebiae Radix. These compounds possess multiple biological activities such as antimicrobial, antioxidant, cardiovascular protective, liver protective, anti-liver fibrosis, antiviral and anticancer activities. The phenylpropanoid pathway in plants is responsible for the biosynthesis of caffeic acid and its oligomers. Glycosylation can change phenylpropanoid solubility, stability and toxic potential, as well as influencing compartmentalization and biological activity. In view of the important role played by de-glycosylation in the regulation of phenylpropanoid homeostasis, the biosynthesis of caffeic acid and its oligomers are supposed to be under the control of relative UDP-glycosyltransferases(UGTs). Through the data mining of Arnebia euchroma transcriptome, we cloned 15 full-length putative UGT genes. After recombinant expression using the prokaryotic system, the crude enzyme solution of the putative UGTs was examined for the glycosylation activities towards caffeic acid and rosmarinic acid in vitro. AeUGT_01, AeUGT_02, AeUGT_03, AeUGT_04 and AeUGT_10 were able to glycosylate caffeic acid and/or rosmarinic acid resulting in different mono-and/or di-glycosylated products in the UPLC-MS analyses. The characterized UGTs were distantly related to each other and divided into different clades of the phylogenetic tree. Based on the observation that each characterized UGT exhibited substrate or catalytic similarity with the members in their own clade, we supposed the glycosylation abilities towards caffeic acid and/or rosmarinic acid were evolved independently in different clades. The identification of caffeic acid and rosmarinic acid UGTs from A. euchroma could lead to deeper understanding of the caffeic acid oligomers biosynthesis and its regulation. Furthermore, these UGTs might be used for regiospecific glycosylation of caffeic acid and rosmarinic acid to produce bioactive compounds for potential therapeutic applications.
Boraginaceae/genetics* ; Caffeic Acids ; Chromatography, Liquid ; Cinnamates ; Cloning, Molecular ; Depsides ; Glycosyltransferases/genetics* ; Phylogeny ; Tandem Mass Spectrometry