Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease (IBD). Huanglian Ganjiang decoction (HGD), derived from ancient book Beiji Qianjin Yao Fang, has demonstrated efficacy in treating UC patients traditionally. Previous research established that the compatibility of cold herb Coptidis Rhizoma + Phellodendri Chinensis Cortex (CP) and hot herb Angelicae Sinensis Radix + Zingiberis Rhizoma (AZ) in HGD synergistically improved colitis mice. This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice. The experimental colitis model was established by administering 3% dextran sulphate sodium (DSS) to mice for 7 days, followed by CP, AZ and CPAZ treatment for an additional 7 days. M1/M2 macrophage polarization levels, glucose metabolites levels and pyruvate dehydrogenase kinase 4 (PDK4) expression were analyzed using flow cytometry, Western blot, immunofluorescence and targeted glucose metabolomics. The findings indicated that CP inhibited M1 macrophage polarization, decreased inflammatory metabolites associated with tricarboxylic acid (TCA) cycle, and suppressed PDK4 expression and pyruvate dehydrogenase (PDH) (Ser-293) phosphorylation level. AZ enhanced M2 macrophage polarization, increased lactate axis metabolite lactate levels, and upregulated PDK4 expression and PDH (Ser-293) phosphorylation level. TCA cycle blocker AG-221 and adeno-associated virus (AAV)-PDK4 partially negated CP's inhibition of M1 macrophage polarization. Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate (DCA) partially reduced AZ's activation of M2 macrophage polarization. In conclusion, the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming. Specifically, CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition, while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.
Animals ; Drugs, Chinese Herbal/chemistry* ; Mice ; Macrophages/immunology* ; Glucose/metabolism* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics* ; Male ; Mice, Inbred C57BL ; Humans ; Colitis/drug therapy* ; Disease Models, Animal ; Colitis, Ulcerative/drug therapy* ; Metabolic Reprogramming

Objective To explore the role of protective function of Sestrin2(Sesn2)to mitochondria in alleviating cognitive dysfunction in mice with sepsis-associated encephalopathy(SAE).Methods 6-week-old male C57BL/6J mice were randomly divided into three groups:sham group,CLP group and CLP plus eupatilin group,40 mice in each group.A sepsis model was induced by cecal ligation and perforation(CLP).The CLP plus eupatilin group was treated with eupatilin.Neurobehavioral test and Morris water maze(MWM)were used to deter-mine neurobehavior and spatial learning and memory function in mice.The number of neurons in hippocampal CA1 area was counted by Nissl staining.HT22 cells were randomly divided into a control group(Con),lipopolysaccha-ride group(LPS),LPS plus eupatilin treatment group(LPS plus eupatilin)and LPS plus eupatilin and Nrf2 siRNA treatment group(LPS plus eupatilin and si-Nrf2).Apoptosis was analyzed by terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)staining,Mitochondrial membrane potential(MMP)was used to analyze mitochondrial damage.Results Seven days after CLP,as compared with sham mice,Sesn2 in hippocampus and cortex decreased significantly in CLP mice(P<0.01).As compared with CLP group,the survival rate in CLP plus eupatilin group increased significantly(P<0.05).As compared with sham group,the mice in CLP group showed a relatively high nerve injury score(P<0.05),and had fewer platform crossings and shorter target stay time,while the mice in CLP plus eupatilin group exhibited a lower injury score(P<0.05),and stayed in the target area for a longer time(P<0.05).As compared with sham group,the co-localization rate of neurons,Sesn2 and Nrf2 in CLP group decreased significantly(P<0.05),and the number of CD68/Iba-1 positive microglia increased significantly(P<0.05),while CLP plus eupatilin group reversed these changes.As compared with Con group,apoptosis and MMP level in LPS group increased significantly(P<0.01),while apoptosis and MMP level in LPS plus eupatilin group were lower than those in LPS group(P<0.05).However,Nrf2 knockdown(LPS plus eupatilin and si-Nrf2 group)reversed the anti-apoptosis and mitochondrial protection of eupatilin.Conclusions Eupatilin can alleviate cognitive dysfunction and neurological deficit in SAE mice by activating Sesn2-Nrf2 pathway,and improve inflammatory microenvironment by alleviating mitochondrial dysfunction.

Objective:To summarize the clinical features of children with pneumonia caused by coinfection of human adenovirus type 7 and Mycoplasma pneumoniae.Methods:A total of 36 children with pneumonia caused by coinfection of human adenovirus type 7 and Mycoplasma pneumoniae (coinfection group) diagnosed in the Wuhan Children′s Hospital from December 1, 2018 to September 1, 2019 were enrolled.Their clinical manifestations, laboratory examinations, and imaging findings were retrospectively analyzed.In the same period, 94 children with single human adenovirus type 7 infection pneumonia were selected as the single infection group.Differences between 2 groups were compared using the Student′s t-test, rank sum test and Chi- square test. Results:In the coinfection group, 25 cases were males, 11 cases were females, their mean age was 3.11 years.The main clinical manifestations included fever (97.2%) and cough (100.0%). The mean body temperature was 40.0 ℃, with the thermal peak of 4 times per day, and the mean course of fever of 11 days.The incidence of severe pneumonia was significantly higher in coinfection group (86.1%) than that of single infection group (69.1%) ( χ2=3.878, P<0.05). The common complications included myocardial damage (55.5%), heart failure (16.7%), liver function damage (25.0%), gastrointestinal bleeding (5.5%), toxic encephalopathy (11.0%), hemophagocytic syndrome (16.7%), and bronchiolitis obliterans (50.0%). The levels of cytokines like interleukin (IL)-6 [237.84(108.59, 606.36) ng/L], IL-10[31.44(12.13, 69.60) ng/L]and interferon-γ [(102.85±92.23) ng/L] were obviously elevated, and among them, IL-6 and IL-10 elevations were significantly pronounced in coinfection group than that of single infection group[148.35(57.43, 390.82); 19.67(10.96, 35.35)] ( Z=-1.984, -2.077, all P<0.05). Lung consolidation (50.0%) and pleural effusion (38.9%) were common in coinfection group, and the incidence of pleural effusion in coinfection group was significantly higher than that of single infection group (19.1%)( χ2=5.594, P<0.05). Conclusions:Most of the pneumonia caused by human adenovirus type 7 mixed Mycoplasma pneumoniae in children is severe pneumonia, which may be related to the cytokine storm.

Objective: To explore the influence of birth weight and growth patterns during infancy on overweight and obesity among first grade primary school pupils, so as to provide a theoretical basis for the formulation of early life prevention and intervention policies. Methods: In 2019, data related to routine physical examinations were collected for primary school pupils in the Minhang District of Shanghai, and information regarding birth and follow ups was collected retrospectively. Physical examination data of 4 434 pupils at 12 months of age were obtained. A multiple linear regression model was used to analyze the relationship between growth patterns during infancy and body mass index (BMI) in the first grade of primary school. A generalized linear model was employed to analyze the relationship between birth weight and growth patterns during infancy and overweight and obesity in the first grade of primary school. A hierarchical analysis was conducted. Results: A linear relationship was observed between growth patterns during infancy and BMI and the BMI Z score of first grade primary school pupils [ β(β 95%CI)=0.30(0.24-0.35),0.12(0.10- 0.15 ), P <0.01]. In addition to subjects classified as small for gestational age (SGA), catch up growth during infancy was identified among subjects who were classified as appropriate for gestational age (AGA) and large for gestational age (LGA). LGA at birth and catch up growth during infancy were independent risk factors for overweight and obesity among first grade primary school children ( RR =1.31-1.55, P <0.05). The hierarchical analysis showed that catch up growth increased the risk of overweight and obesity among first grade primary school pupils classified as AGA [ RR(RR 95%CI )=1.74(1.42-2.14),1.87(1.56-2.26)], and increased the risk of obesity among first grade primary school pupils classified as SGA and LGA [ RR(RR 95%CI )=3.74(1.04-13.49),3.24(1.62-6.46)]( P <0.05). Among those who exhibited catch up growth during infancy, LGA increased the risk of obesity among first grade primary school pupils ( RR= 2.60 , 95%CI=1.35-5.02, P <0.01), but not the risk of being overweight ( P =0.13). Conclusion Birth weight and growth patterns during infancy have an impact on overweight and obesity among children in the first grade of primary school. It is suggested that attention should be paid to growth and physical development in early life for those classified as LGA and AGA, and catch up growth in children should be closely monitored.

Root position plays an important role in healthy, stable, and aesthetic orthodontic treatment. In the past, two-dimensional radiographic images were used to assess the accuracy and precision of tooth root positions. In recent years, the use of cone beam CT (CBCT) and its reconstructed images to measure the three-dimensional spatial position and angle of root position has become mainstream. The root position is mainly described by measuring the relationship between the root and adjacent structures in the buccolingual, vertical, and mesiodistal directions as well as the root angle. The thickness of the alveolar bone on the buccolingual side of the root represents the buccolingual position, the vertical height in the alveolar bone and the relationship between apex and maxillary sinus represents the vertical position, the interroot alveolar bone thickness represents the mesiodistal position of the root, and the root angle is mostly based on incisal mandibular plane angle, angulation, torque, and other angles in the traditional two-dimensional measurement. Fitting CBCT and digital model data can be used to monitor the relationship between root and alveolar bone during orthodontic treatment, but a more comprehensive, standardized three-dimensional tooth root position measurement method is required to make full use of the root data provided by CBCT to study the relative optimal position of the tooth root at different anatomical levels, which combines with computer technology to optimize the digital design of orthodontic diagnosis and treatment.

An increasing number of studies have demonstrated that exosomes are closely associated with liver fibrosis and mediate the process of liver fibrosis by participating in cytokine secretion, macrophage activation, extracellular matrix remodeling, and hepatic stellate cell activation. This article summarizes that the resolution of liver fibrosis requires the reduction of pro-inflammatory and fibrotic cytokines, the reduction of extracellular matrix protein production, the increase of collagenase activity, and finally the loss of activated myofibroblasts. It is believed that exosomes play an important role in the treatment of liver fibrosis and are potential markers for diagnosis and treatment, and in future studies, it is necessary to improve exosome extraction techniques and standardization of treatment quantification.

【Objective】 To observe the characteristics and correlation analysis of thromboelastogram (TEG) and platelet related indexes in patients with preeclampsia in late pregnancy. 【Methods】 88 patients with preeclampsia in late pregnancy treated in the Obstetrics Department of Shanghai Ninth People′s Hospital (Northern Hospital) from June 2017 to June 2020 were selected as observation group, and 288 normal pregnant women in late pregnancy with normal prenatal examination were selected as the control. The median elbow vein blood of the two groups were sampled. The TEG and coagulation related indexes of the two groups were compared, and the relationship between TEG and coagulation related indexes in patients with preeclampsia were analyzed. 【Results】 The K, MA, TT, INR and PLT value in the observation group, relative to controls, were significantly higher (P<0.01), but Angle, PT, and APTT value were significantly lower (P<0.01). The variance K and MA were negatively correlated with PT and APTT (P<0.05), but positively correlated with TT, INR and Plt (P<0.05). Angle was positively correlated with PT and APTT (P<0.05), but negatively correlated with TT, INR and Plt(P<0.05). 【Conclusion】 Routine TEG detection can effectively evaluate the coagulation state of patients with preeclampsia, who are often accompanied by coagulation dysfunction, help to guide clinical early prevention and intervention, and reduce the risk of perinatal hemorrhage and embolism diseases, which is worthy of popularizing in clinical.

Flavaspidic acid AB is a bicyclic phloroglucinol derivative with various biological activities in Dryopteris fragrans (L.) Schott. The structure of flavaspidic acid AB was analyzed by inverse synthesis techniques, and its synthesis was designed under the principle of association. Using phloroglucinol as raw material, the 2-methyl-4-butyrylphloroglucinol was synthesized by Vilsmeier-Haack reaction, reduction and acylation, and the flavaspidic acid fragment was synthesized by acylation, alkylation and deacylation, after which N, N-dimethylmethyleneammonium iodide was activated and the flavaspidic acid AB was obtained. The structures of intermediates and flavaspidic acid AB were confirmed by MS, 1H NMR and 13C NMR, and the yield of the target product reached 14.7%. Results indicate that the designed synthetic route of flavaspidic acid AB is simple and easy.

Objective To evaluate the dynamic changes of left ventricular mechanical synchrony in the early period after acute myocardial infarction (AMI) by two-dimensional speckle tracking imaging (2D-STI) and real time three-dimensional echocardiography (RT-3DE),and analyze the correlation with phase analysis of single photo emission computed tomography gated myocardial perfusion imaging (SPECT GMPI) in porcine models,and further to investigate the clinical significance of left ventricular mechanical dyssynchrony in patients with AMI.Methods Bama minipigs(n =11) were subjected to left anterior descending (LAD) occlusion by balloon to introduce AMI porcine models.All animals underwent 2D-STI and RT-3DE at the baseline (before AMI),1 day,1 week and 4 weeks after LAD occlusion,respectively.In addition,SPECT GMPI was measured at baseline and 1 day after AMI.Data was analyzed and compared the dynamic changes of left ventricular mechanical synchrony before and after AMI.Then the correlation between echocardiography and SPECT GMPI in evaluating left ventricular mechanical synchrony before and after AMI were calculated.Results Eight pigs were successfully established as AMI models and complete the study.SPECT GMPI,2D-STI and RT-3DE showed that the left ventricular mechanical synchrony indexes were significantly higher at 1 day after AMI than those before AMI,which means the appearance of left ventricular mechanical dyssynchrony.Compared with those 1 day after AMI,GLS,Time SD,Tmsv16-SD％ and Tmsv16-Dif％ did not change significantly at 1 week after AMI,but they significantly increased at4 weeks after AMI (all P ＜0.05).At baseline and 1 day after AMI,the GLS measured by 2D-STI and the SPECT GMPI parameter phase bandwidth (BW) showed good correlation(r =0.708-0.719,P ＜0.05),Time SD was significantly correlated with the SPECT GMPI parameter phase standard deviation (SD)(r =0.717-0.830,P ＜0.05),while Tmsv16-Dif％ derived from RT-3DE had a better positive correlation with BW (r =0.713-0.857,P ＜0.05),as similar as Tmsv16-SD％ with SD(r =0.803-0.957,P ＜0.05).Conclusions Left ventricular mechanical dyssynchrony is present 1 day after AMI.Compared with that 1 day after AMI,left ventricular mechanical dyssynchrony doesn't change significantly at 1week after AMI,but further aggravates at 4 weeks after AMI.The parameters of 2D-STI and RT-3DE have good correlation with the mechanical synchrony parameters measured by SPECT GMPI.2D-STI and RT-3DE can be used as reliable methods to evaluate left ventricle mechanical dyssynchrony early after AMI.

The isolated type of orofacial cleft, termed non-syndromic cleft lip with or without cleft palate (NSCL/P), is the second most common birth defect in China, with Asians having the highest incidence in the world. NSCL/P involves multiple genes and complex interactions between genetic and environmental factors, imposing difficulty for the genetic assessment of the unborn fetus carrying multiple NSCL/P-susceptible variants. Although genome-wide association studies (GWAS) have uncovered dozens of single nucleotide polymorphism (SNP) loci in different ethnic populations, the genetic diagnostic effectiveness of these SNPs requires further experimental validation in Chinese populations before a diagnostic panel or a predictive model covering multiple SNPs can be built. In this study, we collected blood samples from control and NSCL/P infants in Han and Uyghur Chinese populations to validate the diagnostic effectiveness of 43 candidate SNPs previously detected using GWAS. We then built predictive models with the validated SNPs using different machine learning algorithms and evaluated their prediction performance. Our results showed that logistic regression had the best performance for risk assessment according to the area under curve. Notably, defective variants in MTHFR and RBP4, two genes involved in folic acid and vitamin A biosynthesis, were found to have high contributions to NSCL/P incidence based on feature importance evaluation with logistic regression. This is consistent with the notion that folic acid and vitamin A are both essential nutritional supplements for pregnant women to reduce the risk of conceiving an NSCL/P baby. Moreover, we observed a lower predictive power in Uyghur than in Han cases, likely due to differences in genetic background between these two ethnic populations. Thus, our study highlights the urgency to generate the HapMap for Uyghur population and perform resequencing-based screening of Uyghur-specific NSCL/P markers.
Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Cleft Lip ; genetics ; Cleft Palate ; genetics ; Genome-Wide Association Study ; Humans ; Infant ; Logistic Models ; Machine Learning ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Single Nucleotide ; Retinol-Binding Proteins, Plasma ; genetics ; Risk Assessment