Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IκBα) and then activate nuclear factor kappa-B (NF-κB). Inhibition of IKKβ has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKKβ is constitutively activated in healthy donors and healthy Ikkβ ^C46A (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKKβ-IκBα-NF-κB signaling activation. These indicate that IKKβ activation probably plays homeostatic role instead of causing inflammation. Compared to Ikkβ ^WT littermates, lipopolysaccharides (LPS) could induce high mortality rate in Ikkβ ^C46A mice which is correlated to breaking the homeostasis by intensively activating p-IκBα-NF-κB signaling and inhibiting phosphorylation of 5' adenosine monophosphate-activated protein kinase (p-AMPK) expression. We then demonstrated that IKKβ kinase domain (KD) phosphorylates AMPKα1 via interacting with residues Thr183, Ser184, and Thr388, while IKKβ helix-loop-helix motifs is essential to phosphorylate IκBα according to the previous reports. Kinase assay further demonstrated that IKKβ simultaneously catalyzes phosphorylation of AMPK and IκBα to mediate homeostasis. Accordingly, activation of AMPK rather than inhibition of IKKβ could substantially rescue LPS-induced mortality in Ikkβ ^C46A mice by rebuilding the homeostasis. We conclude that IKKβ activates AMPK to restrict inflammation and IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.

Objective:To investigate the safety and therapeutic effect of Shakubatrivalsartan in the treatment of pediatric dilated cardiomyopathy.Methods:Clinical information, treatment and prognosis of 5 cases with dilated cardiomyopathy in the First Affiliated Hospital of Xinxiang Medical University from June 2018 to December 2020 were retrospectively analyzed, and relevant literatures were reviewed.Results:A total of 5 cases of children with dilated cardiomyopathy were analyzed, including 3 males and 2 females with age of 12-17 years.Their median left ventricular ejection fraction (LVEF), left ventricular end diastolic dimension (LVDd), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were 37% (20%-41%), 61 mm (59-67 mm), and 13 250 ng/L (12 310-21 823 ng/L), respectively.The median conventional treatment time was 5 months (1-12 months), in which, the condition of heart failure gradually progressed, and the median LVEF, LVDd and NT-proBNP levels were reduced to 33% (19%-37%), 61 mm (60-74 mm), 13 144 ng/L (8 086-15 137 ng/L). After less than 3 months of follow-up following conventional treatment plus Shakubatrivalsartan, NT-proBNP level significantly decreased in 5 cases.Besides, 4 cases had improved cardiac function, and the other one′s improvement was not obvious.The blood pressure of 5 cases decreased at varying degrees after medication of Shakubatrivalsartan, which should be closely monitored during drug titration.No adverse reactions were reported.Conclusions:Shakubatrivalsartan for the treatment of pediatric dilated cardiomyopathy is safe and effective, which can alleviate or reverse the process of myocardial remodeling and improve cardiac ejection fraction, thus improving the prognosis.

A lack of effective drugs and technical means to eradicate hepatitis B virus (HBV) is a bottleneck that limits the ability to fully cure HBV infection. Recently, genome-editing technology based on clustered regularly interspaced short palindromic repeats -associated protein 9 is an emerging technique for editing specific gene loci, which can specifically target HBV covalently closed circular DNA, effectively inhibits HBV DNA replication and regulates HBV functional protein expression, and is expected to become a powerful gene therapy tool for the complete eradication of HBV. Considering this, it has become the focus of attention for scholars at home and abroad that how to use clustered regularly interspaced short palindromic repeats -associated protein 9 to accomplish modification of HBV genomes for complete eradication of HBV. This paper summarizes the latest progress based on the latest research results at home and abroad in the application of clustered regularly interspaced short palindromic repeats -associated protein 9 gene editing technology in anti-HBV infection treatment, and expounds its potential and challenges as a radical cure for HBV infection.

Objective To investigate the genetic association between KCNJ10 rs1890532 gene polymorphism and susceptibility to children epilepsy in the Han descent population in the Northern China. Methods Two hundred twelve children with epilepsy were recruited as the epilepsy group. According to seizure types, they were divided?into partial seizures (PS) group (120 cases) and generalized seizures (GS) group (92 cases). Two hundred healthy volunteers without epilepsy were randomly selected from our hospital during the same period as the control group. General clini-cal data was collected and genotype was determined by polymerase chain reaction- restriction fragment length poly-morphism for the polymorphism of the KCNJ10 gene. Results Results showed that KCNJ10 rs1890532 gene polymor-phism was significantly associated with GS in children in both allelic association analysis (OR=1.325, 95%CI 1.014~2.461, P=0.043) and recessive model (OR=3.173, 95%CI 1.097~10.694, P=0.021) after adjustment for sex and age. There was no significant difference in any genetic model between the control group and epilepsy group, neither be-tween the control group and PS group. Conclusion Polymorphism of the KCNJ10 (rs1890532) gene may be associated with the risk of GS in children.

Objective To investigate the effect and influence on inflammatory factors of salbutamol aerosol combined with montelukast in treatment of cough variant asthma.Methods From Jan 2015 to Jan 2016,120 cases of cough variant asthma in our hospital were selected as the subjects.They were randomly and equally divided into 2 groups:control group (n =60) were treated with salbutamol aerosol,and observation group were treated with salbutamol aerosol and montelukast.The clinical effects,the pulmonary function and the serum inflammatory factors were compared between the two groups.Results After 2 months of treatment,the effective rate of the control group and the observation group were 73.3％ and 96.7％ respectively,there was statistical differences between two groups (P ＜ 0.05).The FEV1 and FEV1/FVC of both groups showed remarkable increase.The FEV1,FEV1/FVC of observation group were (2.21 ± 0.17) L,(66.10 ± 4.46)％,and the FEV1,FEV1/FVC of control group (1.82 ± 0.11) L,(52.48 ± 3.34)％.The difference between two groups was statistically significant (P ＜ 0.05).The IL-6 and TNF-α of both groups showed remarkable decrease.IL-6 and TNF-α in observation group were significantly lower than those of control group (14.58 ± 2.90 vs.20.87 ± 3.26,P ＜ 0.05;0.59 ± 0.12 vs.0.97 ± 0.15,P ＜ 0.05).Conclusion The use of montelukast combined with salbutamol aerosol in the treatment of cough variant asthma was safe and effective,and could significantly improve pulmonary function and reduce inflammatory factor.

Objective To explore the clinical effect and influence on congnitive function of single use ofvalproate,oxcarbazepine,and levetiracetam in treatment of children epilepsy.Methods Children with epilepsy (96 cases) accepted in Weinan Matemty and Child Health Care Hospital from April 2011 to January 2016 were randomly divided into groups A,B,and C.Children in those three groups were given valproate,oxcarbazepine,and levetiracetam,respectively.Then the clincial efficacy,changes of EEG and congnitive function,and safety were compared.Results The total effective rates of groups A,B and C were 71.88％,78.13％,and 90.63％,respectively,group C was little higher than groups A and B without statistically significance.The epileptiform discharge improvement rate was getting better following extended therapy.The improvement rate of group C was better than that of group B and even much better than that of group A with statistically significance (P ＜ 0.05).The verbal IQ (VIQ),performance IQ (PIQ),and full scale IQ (FIQ) of three groups before treatment had no big difference,but the scores of groups B and C were much better than before and group A after treatment with statistically significant difference (P ＜ 0.05).The adverse reaction rates of groups A,B,and C were 28.13％,12.50％,and 3.13％,respectively with statistically significant difference among them (P ＜ 0.05).Conclusion Valproate,oxcarbazepine,and levetiracetam have similar effect in treatment of children epilepsy,but oxcarbazepine and levetiracetam have positive significance in EGG and recognition function improvement.And the safety of levetiracetam is the highest of three drugs,which is worth of clincial application.

Objective To investigate the differences of expression and activation of natural killer (NK) cell G2D (NKG2D) in patients with different immune status of chronic hepatitis B virus (HBV) infection, and to explore the significance of NKG2D-mediated immune injury in HBV infection.Methods Fifteen chronic HBV carriers (immune tolerance),15 chronic hepatitis B (CHB, immune activation) patients, 15 HBV-related acute/subacute-on-chronic liver failure (HBV-ACLF, immune over-activation) patients were enro1led in this study from January 2010 to December 2011 in the Third Hospital of Hebei Medical University.The frequencies of NK cells and NKG2D+ NK cells in peripheral blood mononuclear cells (PBMC) were detected by flow cytometry.The NKG2D mRNA expressions were measured by real-time fluorescent quantitative polymerase chain reaction.Localization and hemi-quantitative analysis of NKG2D+ cells in liver tissue were performed by immunohistochemistry staining.Concentrations of serum interferon(IFN)-γ, tumor necrosis factor(TNF)-α, perforin and granzyme B were quantified by enzyme 1inked immunosorbent assay (ELISA).Normally distributed continuous variables were analyzed using one-way analysis of variance (ANOVA), followed by Student-Newman-Keuls q test for evaluating variances between each two groups.For non-normally distributed data or heterogeneity of variance, differences between groups were analyzed using nonparametric Kruskal-Wallis H test, followed by Nemenyi test for pairwise comparisons.Pearson chi-square test was used to analyze categorical variables.Results The percentages of NK cells in PBMC were (13.58±3.24)% in healthy controls, (5.42±2.18)% in chronic HBV carriers, (7.92±2.85)% in HBV-ACLF group and (8.43±2.92)% in CHB group.The percentage of NK cells in PBMCs was lower in each chronic HBV-infected group compared with healthy controls (F=22.04, P<0.05).The frequency of NKG2D+ NK cells in HBV-ACLF group (18.92±5.85)% was the highest, followed by CHB group (12.85±3.39)%, healthy controls (8.45±2.86)%, and chronic HBV carriers (3.36±1.05%), with the statistically significant differences between each two groups (H=46.09, P<0.01).Intrahepatic NKG2D mRNA expression and NKG2D+ cells density were highest in HBV-ACLF group (6.58±1.86 and 30.69±6.67, respectively), followed by CHB group (3.25±0.95 and 17.36±4.13, respectively) and chronic HBV carriers (0.69±0.20 and 3.16±1.24, respectively), with the statistically significant differences between each two groups (H=52.10 and 52.73 respectively, both P<0.01).The similar patterns were observed in serum IFN-γ, TNF-α, perforin and granzyme B concentrations.Conclusions NKG2D expresses variously in patients with different immune status of chronic HBV infection.Activation of NKG2D may take part in the immune pathogenesis of chronic HBV infection.

Objective: To investigate the knowledge of nonalcoholic fatty liver disease (NAFLD) among medical staff and general population in Hebei Province, China, understand the degree of awareness of NAFLD among residents, standardize the diagnosis and treatment of NAFLD, improve the correct awareness of NAFLD among general population, promote the establishment of a reasonable lifestyle, and scientifically and effectively control the incidence and mortality rates of NAFLD. Methods: The investigation was performed in 30 hospitals and neighboring schools and communities in Hebei Province, and a questionnaire survey on the knowledge of NAFLD was performed for 1 300 medical workers and 2 000 persons from the general population. EpiData3.1 software was used to input data, and SPSS21.0 was used for statistical analysis. The chi-square test was used for comparison of rates between groups. Results: Of all medical staff, 39.0% knew that liver biopsy was the gold standard for the diagnosis of NAFLD; 63.7% thought liver biopsy had the highest diagnostic value, followed by liver ultrasound (61.0%) and liver CT (48.1%); only 1.2% thought improvement of insulin resistance was the preferred treatment for NAFLD. Among 486 medical workers who had participated in the diagnosis and treatment of NAFLD, only 1.2% thought that the patients had good compliance. Of all persons from the general population, 15.2% thought NAFLD was infectious and 58.6% thought NAFLD might progress to liver cirrhosis or liver cancer. Of all respondents with body mass index ≥28 kg/m², 17.8% did not know that he/she had obesity, and as high as 55.8% were obese or did not control body weight within the past 1 year. Of all NAFLD patients, 50.5% were complicated by hyperlipidemia, 18.5% were complicated by diabetes, and 29.5% were complicated by hypertension; 43.0% had not received standardized treatment, and among the other 57.0% respondents who received treatment, 79.0% were given non-drug treatment such as reasonable diet and physical exercise. In NAFLD patients who were not improved after treatment, the major cause of failure was that they were not able to stick to healthy living habits. Most NAFLD patients were willing to obtain the knowledge of disease through television, website, and newspaper. Conclusion Medical staff do not have enough awareness of NAFLD, and some of them cannot perform standardized diagnosis and treatment of NAFLD with reference to clinical guidelines. Therefore, the education on NAFLD should be enhanced for medical staff to guide them to perform accurate screening, diagnosis, evaluation, and treatment of NAFLD. The general population has low awareness of NAFLD and NAFLD patients have poor treatment compliance, which are important causes of increased incidence rate of NAFLD and disease progression. The general population should be educated about NAFLD to help them establish a reasonable lifestyle.

ObjectiveTo explore the relationship between serum uric acid and prehypertension and the effects of age,obesity,fasting glucose and lipids in Chinese adults.Methods14,451 non-hypertensive cases from a community-based health examination survey in Xuzhou,Jiangsu province of China were enrolled in this study.Blood pressure,BMI,and determination of fasting glucose,lipids and serum uric acid were measured in all cases.ResultsThe odds ratios ( OR,95％ CI ) of prehypertension across increased serum uric acid after adjusting for age,sex were 1.0,1.20 ( 1.07 - 1.35 ),1.55 ( 1.36 - 1.76),1.82(1.60-2.09),2.33(2.03-2.67) (Pfor trend ＜0.01).The odds ratios were 1.0,1,04(0.92-1.18),1.21(1.06-1.38),1.26(1.09 - 1.45),1.36(1.17 - 1.58),( Pfor trend ＜0.01) after adjusting for age,sex,BMI,glucose,and lipids.In addition,fasting glucose significantly interacted with uric acid ( P for interaction ＜ 0.01 ).Conclusions Serum uric acid was associated with prehypertension,which might be an independent metabolic risk factor.Fasting glucose may reinforce the associations.

Objective To detect the gene mutation of thyroid hormone receptor β ( TRβ ) in a family with thyroid hormone resistance syndrome.Methods The genomic DNA was extracted from peripheral blood leukocytes of the patient and his 5 family members.The exons 1-10 ofTRβ gene were amplified by PCR.The products of PCR were sequenced directly to detect the gene mutation.Results Two members of this family were confirmed to have the C y A transition mutation at nucleotide 1642 site within exon 10 of TRβ gene,which was a missense mutation causing the substitution of Proline to Threonine (P453T).The mutation was Heterozygous.Conclusions It was confirmed that the patient has TRβ gene mutation P453T in exon 10.The mutation may lead to the occurrence of thyroid hormone resistance syndrome.