OBJECTIVE To investigate the improvement effects of Runchang granules on the constipation in mice and its potential mechanism. METHODS The mice were randomly divided into normal control group， model group， Runchang granules low-dose and high-dose groups （5， 10 g/kg）， mosapride group （0.003 g/kg， positive control）， with 6 mice in each group. The latter 4 groups were given loperamide intragastrically （0.004 g/kg）， twice a day， for 3 consecutive days. Normal control group and model group were given purified water intragastrically， and administration groups were given relevant medicine intragastrically for 7 consecutive days. After the last medication， fecal moisture content and intestinal motility of mice were determined， while the structures of colon and ileum， and the secretion of colonic mucus were observed. Protein expressions of tyrosine kinase receptor （c-kit）， mucin 2 （MUC2） and stem cell factor （SCF） were determined in colon； meanwhile， the mRNA expression levels of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， inducible nitric oxide synthase （iNOS）] as well as factors related to promoting intestinal motility [neuronal nitric oxide synthase （nNOS）， smooth muscle myosin light chain kinase （smMLCK）， 5-hydroxytryptamine 4 receptor （5-HT4R）， MUC2， SCF， c-kit] were determined. RESULTS Compared with model group， the fecal water content， intestinal propulsion rate， protein expression of c-kit in colon， relative expressions of MUC2 and SCF protein， and mRNA expressions of factors related to promoting intestinal motility （except for nNOS and SCF in Runchang granules low-dose group） were all increased significantly in Runchang granules low-dose and high-dose groups， and mosapride group （P＜0.05 or P＜0.01）. mRNA expression levels of inflammatory factors were decreased significantly（P＜0.05 or P＜0.01）. Both colon and ileum injuries improved， and the secretion of colon mucus was increased significantly in Runchang granules high-dose group （P＜0.01）. CONCLUSIONS Runchang granules have laxative effect and can improve constipation in mice， and its mechanism may be related to the promotion of the secretion of colon mucus and MUC2 expression， and the activation of SCF/c-kit signaling pathway.

Objective:To summarize the clinical phenotype and genetic characteristics of children with neurodegeneration caused by UBTF gene mutations in childhood. Methods:The clinical and genetic data of 3 children with neurodegeneration in childhood diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University from February 2020 to January 2023 were retrospectively analyzed. All the 3 probands were found having UBTF gene mutations through the whole exome gene sequencing, and the first generation Sanger sequencing method was used to verify the UBTF gene in their family members. The variation characteristics of the UBTF gene were analyzed, and the treatment and follow-up results of the 3 children were summarized. Results:Among the 3 children with childhood onset neurodegeneration, 2 were male and 1 female, aged 9 months, 4 years and 6 months after birth, respectively. The clinical phenotypes mainly included motor retardation, speech and mental retardation, and dystonia. Among them, case 1 and case 2 had seizures, case 1 had dysphagia, feeding problems, no weight gain and ataxia. Brain MRI plain scan showed that case 1 and case 2 had different degrees of cerebral atrophy, case 1 had hypoplasia of corpus callosum, ventricle expansion and softening focus, and case 3 showed non-specific widening of the subarachnoid space. There were no abnormalities in the chromosome copy number variation and mitochondrial ring gene testing in the 3 children; the whole exon gene testing suggested the de novo missense variant in the UBTF gene [NM_014233.4: c.1414(exon14) G>A (p.Gly472Ser), c.1392(exon14)G>T(p.Lys464Asn)] and the maternal nonsense variant [NM_014233.4:c.520C>T(p.Arg174 *)], which were unreported site variants. In terms of treatment, the 3 children received comprehensive rehabilitation function training, and achieved a certain degree of language and intelligence improvement. Seizure control was effectively managed in case 1 with a single antiepileptic drug. Epileptic seizures were effectively treated and controlled in case 2 using more than 4 types of antiepileptic drugs. Conclusions:Neurodegenerative changes caused by UBTF gene mutations in childhood are relatively rare, and some cases may be accompanied with brain atrophy. De novo missense variation and maternal nonsense variation of the UBTF gene are the genetic etiology of the 3 probands.

Objective:To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ).Methods:Clinical data of three children diagnosed with late-onset MADD at the Children′s Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years.Results:The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c. 1211T>C (p.M404T) and a maternal c. 488-22T>G variant in child 1, a paternal c. 1717C>T (p.Q573X) and a maternal c. 250G>A (p.A84T) variant in child 2, and a paternal c. 1285+ 1G>A and maternal c. 629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B2, levocarnitine and coenzyme Q 10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up. Conclusion:The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.

Background::Hypertension and non-alcoholic fatty liver disease (NAFLD) share several pathophysiologic risk factors, and the exact relationship between the two remains unclear. Our study aims to provide evidence concerning the relationship between hypertension and NAFLD by analyzing data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 and Mendelian randomization (MR) analyses.Methods::Weighted multivariable-adjusted logistic regression was applied to assess the relationship between hypertension and NAFLD risk by using data from the NHANES 2017-2018. Subsequently, a two-sample MR study was performed using the genome-wide association study (GWAS) summary statistics to identify the causal association between hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and NAFLD. The primary inverse variance weighted (IVW) and other supplementary MR approaches were conducted to verify the causal association between hypertension and NAFLD. Sensitivity analyses were adopted to confirm the robustness of the results.Results::A total of 3144 participants were enrolled for our observational study in NHANES. Weighted multivariable-adjusted logistic regression analysis suggested that hypertension was positively related to NAFLD risk (odds ratio [OR] = 1.677; 95% confidence interval [CI], 1.159-2.423). SBP ≥130 mmHg and DBP ≥80 mmHg were also significantly positively correlated with NAFLD. Moreover, hypertension was independently connected with liver steatosis ( β = 7.836 [95% CI, 2.334-13.338]). The results of MR analysis also supported a causal association between hypertension (OR = 7.203 [95% CI, 2.297-22.587]) and NAFLD. Similar results were observed for the causal exploration between SBP (OR = 1.024 [95% CI, 1.003-1.046]), DBP (OR = 1.047 [95% CI, 1.005-1.090]), and NAFLD. The sensitive analysis further confirmed the robustness and reliability of these findings (all P >0.05). Conclusion::Hypertension was associated with an increased risk of NAFLD.

Objective To investigate the distribution characteristics and risk factors of type 2 diabetes mellitus(T2DM)in rural residents of Yangqu county,Shanxi province.Methods In October 2020,a total of 5028 residents aged 18 years and above in rural are-as of Yangqu county,Shanxi province were selected as the research subjects by multi-stage stratified cluster random sampling.Question-naire survey and physical examination were used to conduct the study.Unconditional Logistic regression was used to analyze the risk factors for T2DM.Results In rural areas of Yangqu county,Shanxi province,11.8％(95％CI:10.9％-12.6％)of residents who were aged 18 years and above had T2DM.The prevalence of females was 14.1％(95％Cl:12.9％-15.4％)and males was 8.6％(95％CI:7.4％-9.8％).The results of unconditional Logistic regression showed that female(OR=1.619,95％CI:1.324-1.981),advanced age(OR=5.909,95％CI:2.893-12.072;OR=9.575,95％CI:4.802-19.095;OR=11.779,95％CI:5.896-23.535;OR=8.793,95％CI:4.238-18.244),hypertension(OR=2.468,95％CI:2.013-3.027),hyperlipidemia(OR=2.968,95％CI:2.232-3.947),and family history of diabetes mellitus(OR=7.253,95％CI:5.434-9.682)were significantly associated with T2DM.Conclusion Female,advanced age,hypertension,hyperlipidemia,and family history of diabetes mellitus were the risk factors of T2DM in rural residents of Yangqu county,Shanxi province.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

Objective:To explore the protective effect of methyl eugenol (Me) on islet ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism.Methods:The islets were isolated and purified from 6-8 week male BALB/c mice and divided into four groups of normal control (normal culture without any treatment), hypoxia/reoxygenation (H/R treatment), H/R+ dimethyl sulfoxide (DMSO dosing plus H/R treatment) and H/R+ Me (Me dosing plus H/R). Viability of islet cells in each group was detected by acridine orange (AO)/propidium iodide (PI) double stain.Function of islet cells (insulin secretion) was measured by enzyme-linked immunosorbent assay (ELISA). Murine islet β Min6 cells were selected for detecting the effect of Me on the proliferative activity of normal cultured and H/R treated islet cells under different concentration gradients by CCK8.Then Min6 cells were divided into four groups of normal, H/R, H/R+ DMSO and H/R+ Me.The definition of group was the same as that of primary murine islets.Flow cytometry and Hoechst 33342 nuclear stain were utilized for detecting cell apoptotic rate in each group.The protein expressions of p-JNK, p-p38, JNK, p38, Bcl-2 and Bax were detected by Western blot.And the data were processed by one-way ANOVA or t test.Results:The proportion of dead islet cells in H/R group was (29.47±2.65)% and it was significantly lower than that in normal group (7.63±1.53)%.And the inter-group differences were statistically significant ( P<0.001). The proportion of dead islet cells was (20.63±3.07)% in H/R+ Me group.It was higher than that in H/R group (29.47±2.65)% and in H/R+ DMSO group (30.13±1.50)% and inter-group difference was statistically significant ( P<0.05 & P<0.01). Under the stimulation of high glucose, the insulin secretion level of islet in H/R+ Me group was (1.76+ 0.08) mg/L, which was higher than that in H/R group and H/R+ DMSD group(1.24±0.14)mg/L and(1.27±0.05)mg/L, and the difference was statistically significant[(1.76±0.08) vs. (1.24±0.14) mg/L; (1.76±0.08) vs.(1.27±0.05) mg/L, P<0.01]. There was no significant effect on cell viability after Me dosing within a certain concentration range (0-40 μmol/L). After Me dosing (5 μmol/L), cell viability of H/R-treated Min6 cells was significantly higher than that without Me.And the difference was statistically significant[(1.19±0.03) vs.(1.00±0), P<0.01]. As compared with H/R and H/R+ DMSO groups, overall apoptotic rate declined in H/R+ Me group (Hoechst 33342 stain: 14.50%±1.05% vs. 23.30%±1.18%, 14.50%±1.05% vs. 22.77%±1.75%, P<0.001; Flow cytometry: 4.36%±0.54% vs. 21.44%±1.02%, 4.36%±0.54% vs. 21.68%±3.06%, P<0.01). The expressions of p-JNK and p-p38 were down-regulated (p-JNK: 0.77±0.06 vs. 1.03±0.05, 0.77±0.06 vs.0.93±0.04, P<0.001; p-p38: 0.80±0.05 vs. 1.01±0.08; 0.80±0.05 vs. 1.00±0.05, P<0.05) while Bcl-2/Bax ratio rose (1.62±0.13 vs. 0.72±0.10, 1.62±0.13 vs. 0.74±0.13, P<0.01). Conclusions:Me can improve the viability and function of islets and suppress the apoptosis of Min6 cells after H/R.The mechanism is correlated with JNK and p38 MAPK signaling pathways.

Objective: To investigate the current status and influencing factors of knowledge, attitude, and practice of hypertension prevention and control among rural residents in Shanxi Province, so as to provide insights into implementation of health education pertaining to hypertension control in rural areas. Methods: A total of 7 403 residents were sampled using a multi-stage cluster random sampling method from rural areas of Yangqu, Daning, and Yonghe counties of Shanxi Province from November 2020 to July 2021 for face-to-face questionnaire surveys and physical examinations. Residents' basic characteristics, knowledge, attitude, and practice of hypertension prevention and control, and height, weight, blood pressure were collected, and factors affecting knowledge, attitude, and practice of hypertension prevention and control were identified using a generalized linear model. Results: A total of 7 403 questionnaires were allocated, and 7 031 effective questionnaires were recovered, with an effective response rate of 94.98%. The respondents included 3 035 men (43.17%) and 3 996 women (56.83%), and had a mean age of (58.45±13.75) years. The median scores of hypertension prevention and control knowledge, attitude and practice were 5 (interquartile range, 4), 16 (interquartile range, 5) and 14 (interquartile range, 7) points, with scoring percentages of 48.40%, 80.55% and 54.41%, respectively. Generalized linear model analysis showed that an educational level of junior high school and above, annual family income per capita of ≥4 000 RMB, family history of hypertension, development of hypertension among family members or friends, overweight/obesity and presence of depression resulted in high scores for hypertension prevention and control knowledge; annual family income per capita of ≥10 000 RMB, family history of hypertension, presence of hypertension among family members or friends, mild/severe insomnia and presence of depression resulted in high scores for hypertension prevention and control attitude, while age of ≥65 years and blood pressure of ≥140/≥90 mmHg resulted in low scores for attitude; females, age of ≥45 years, an educational level of junior high school and above, blood pressure of ≥140/≥90 mmHg, family history of hypertension, presence of hypertension among family members or friends and overweight/obesity resulted in high scores for hypertension prevention and control practice, and residents had a low body weight had a low score for practice (all P<0.05). Conclusions The hypertension prevention and control attitude is satisfactory among rural residents in Shanxi Province; however, the hypertension prevention and control knowledge and practice are poor. Health education pertaining to hypertension prevention and control should be strengthened, and personalized health education is needed targeting individuals with a low educational level and low income.

Objective:To investigate the clinical value of fetal ultrasonography in the screening of congenital heart malformations in twins at 11-13 + 6 weeks of gestation. Methods:A retrospective cohort study method was used.Cases were collected from Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital (January 2012 to December 2016) and the Fourth Hospital of Shijiazhuang City (January 2014 to December 2018). The twins with singleton or twins with cardiac malformation were screened out as the cardiac malformation group, and the twins with normal delivery during the same period were selected as the control group. Ultrasound data such as the nuchal translucency (NT), crown-rump-length (CRL), chorionicity, conception method, NT discordance, CRL discordance, NT discordance ≥20% incidence rate between twins, and the CRL discordance ≥10% incidence rate between twins in the two groups at 11-13 + 6 weeks were compared and analyzed. Results:①There were 30 cases in the cardiac malformation group (including 27 twins with singleton cardiac malformation and 3 twins with twin cardiac malformation) and 1 906 cases in the control group. ②The incidence rates of NT value ≥95th percentile and NT value ≥99th percentile in one or two pregnancies were significantly higher in the cardiac malformation group than in the control group (20.00% vs 2.20%, P<0.001; 10.00% vs 0.63%, P=0.002), the area under the ROC curve (AUC) for cardiac malformation screening was 0.589 and 0.549, respectively; CRL discordance in cardiac malformation group was higher than that in control group ( P=0.018), the incidence of CRL discordance ≥10% in the cardiac malformation group was higher than that in the control group (26.67% vs 12.70%, P=0.024), the AUC of cardiac malformation screening was 0.570; there were no significant differences in the incidence of NT discordance, the incidence of NT discordance ≥20%, pregnancy pattern and chorionicity between the two groups (all P>0.05). ③Multivariate Logistic regression analysis was performed using the incidence rates of NT value ≥95% and NT value ≥99%, CRL discordance ≥10%, and NT discordance ≥20%. The incidences of fetal NT value ≥95% and NT value ≥99% were risk factors for cardiac malformation in twins ( OR=11.095, 105.778; 95% CI=4.311-28.558, 16.984-658.796). Conclusions:Ultrasound at 11-13 + 6 weeks of gestation showing thickened value of one or two fetuses, and the CRL discordance≥10%, indicates an increased risk of cardiac malformation in the twins; NT value ≥95% and NT value ≥99% is a risk factor for heart defects in twins.

Objective To investigate the clinical outcome of single kidney transplantation from pediatric donors and to explore the application criteria.Methods The clinical data of 14 recipients undergoing renal transplantation from October 2006 to October 2016 were retrospectively analyzed.All the recipients received primary kidney transplantation from pediatric donor and the renal artery was anastomosed with external iliac artery.Based on the length of the kidney donor,the recipients were divided into two groups as group A (length beyond 6 cm) and group B (length 5-6 cm).The clinical effect and complications of the 14 recipients,the survival of the recipients and grafts,the recovery of renal function,the change of the renal length and the postoperative complications were compared between the two groups.Results The renal length in group A (n =7) was (7.5 ± 1.2) cm,and (5.7 ± 0.1) cm in group B (n =7).During the follow up period,all renal grafts and recipients survived.No significant difference was observed between two groups in renal graft function evaluated by serum creatinine and estimated glomerular filtration rate (eGFR) at 7th day,14th day,1st,2nd,3rd and 6th month postoperatively,P＞0.05.The length of transplanted kidney increased after operation in both groups,with results of 9.9 ± 0.6 cm in group A and 10.4 ± 1.5 cm in group B (P＞0.05),respectively,at 2nd month post-transplantation.Delayed graft function (DGF) occurred in 2 cases of group A and 1 case of group B.Seven cases developed proteinuria (50.0％),including 2 cases in group A (28.6％) and 5 cases in group B (71.4％).Four cases suffered hematuria (28.6％),including 2 cases in group A (28.6％) and 2 cases in group B (28.6％).One recipient in group B suffered acute rejection.No vascular embolization,urine leakage,pulmonary infection and other complications were observed in all the recipients.Conclusion The length beyond 5 cm is acceptable for single pediatric kidney donor for adult recipients with a promising clinical outcome in short-term.However,the high incidence of proteinuria and hematuria remains obstacle,and the long-term outcome needs further exploration.