Ulcerative colitis(UC)is a common disease of the digestive system.Phosphatidylinositol-3-kinase(PI3K)/synuclein/threonine kinase(AKT)is closely related to cell survival,apoptosis,inflammation and other biological processes,and the expression levels of PI3K and AKT significantly increase during the course of UC,with accelerated apoptosis,improved inflammation,and damaged intestinal mucosal barrier function.In recent years,a large number of basic and clinical trials have been conducted on PI3K/AKT signaling pathway in TCM,and the results indicate that PI3K/AKT signaling pathway is expected to be an important potential target for UC treatment.This article analyzed the mechanism of the regulation of PI3K/AKT signaling pathway in TCM from monomer,extract,compound and acupuncture,and suggested that the regulation of this signaling pathway is of great significance for the prevention and treatment of UC,and provide reference for drug development.

Objective To investigate the protective effect of Toll-like receptor (TLR)2/TLR9 agonists,Pam2 CSK4(Pam)and CpG ODN (CpG)on mice infected with Acinetobacter baumannii (Ab)in the lungs.Methods Female C57 mice (6～8 weeks old)were randomly divided into PBS,Pam,CpG and Pam+CpG groups.In 24 h after intranasal immunization with different doses of the corresponding agonists,the mice were given a lethal dose of Ab infection in the lungs,and the survival rates of the mice were observed.A sublethal dose lung infection model of Ab was then established,and the bacterial colonization in the blood,lungs,liver,kidneys and spleen was measured respectively in the mice after infection.HE staining was used to observe the pathological damages in the lungs and kidneys.The protective effect of the agonists in the immunized mice against Ab was examined at 1,3 and 7 d after immunization to explore the protective time window.Pam+CpG was used to stimulate A549 cells and RAW264.7 cells to investigate the killing or phagocytic effects on Ab.Results Compared to PBS,Pam+CpG treatment significantly improved the survival rate of the mice after a lethal dose of Ab lung infection (P<0.05,P<0.01 ),reduced bacterial colonization in the blood (P<0.01 ),lungs (P<0.01 ),liver (P<0.01 ),kidneys (P<0.01 )and spleen (P<0.01 )in the mice after sublethal challenge,and alleviated pathological damage caused by infection. Immunization at 1 or 3 d before infection significantly improved the survival rate (P<0.05 ),and the protective effect was the best in 3 d after immunization.Furthermore,compared to single PBS,Pam and CpG immunization,Pam+CpG significantly promoted the killing and phagocytic effects of A549 epithelial cells and RAW264.7 cells,respectively,against Ab (P<0.01 ).Conclusion Combined application of TLR2/TLR9 agonists exerts a significant protective effect on both lethal and sublethal infections of Ab,which might be by its promoting the killing or phagocytic effect of lung epithelial cells and macrophages against Ab.

Objective This study aims to evaluate the mid-and long-term clinical efficacies of simple taper retentive implants for immediate placement in chronic apical infected teeth in the posterior region.Methods A total of 36 pa-tients with 41 simple taper retentive implants were included in the study conducted.These patients underwent immediate implant treatment for teeth with chronic apical infection in the posterior region.The soft and hard tissues surrounding the implants were assessed and documented over a period of 5 years following the completion of crown restoration.Re-sults During the 5 years follow-up period,one implant failed with mobility,and the implant survival rate was 97.6％.The mean marginal bone resorption was(-0.74±1.03)mm from the immediate post-implant placement to the immediate post-crown restoration,and the difference in marginal bone heights between the two time points was statistically signifi-cant(P＜0.05).The mean marginal bone resorption was(-0.21±0.70)mm from the immediate post-crown restoration to the 5-year post-crown restoration,and the difference in marginal bone height between the two time points was not statisti-cally significant(P＞0.05).No significant difference(P＞0.05)was observed in bone resorption between mesial and distal,maxillary and mandibular,different tooth posi-tions,and different implant lengths.The soft tissue sur-rounding the implants remained healthy at the 5 years follow-up period,one implant exhibited peri-implantitis,and no mechanical complications were observed.The overall satisfaction of patients was good.Conclusion Immediate place-ment of simple taper retentive implants after thorough debridement of chronic infected alveolar socket in the posterior re-gion can achieve good mid-and long-term clinical outcomes after 5 years of loading.The soft and hard tissues were maintained in a steady state,which expanded the indications for immediate implantation.

It is among the goals in metabolic engineering to construct microbial cell factories producing high-yield and high value-added target products, and an important solution is to design efficient synthetic pathway for the target products. However, due to the difference in metabolic capacity among microbial chassises, the available substrate and the yielded products are limited. Therefore, it is urgent to design related metabolic pathways to improve the production capacity. Existing metabolic engineering approaches to designing heterologous pathways are mainly based on biological experience, which are inefficient. Moreover, the yielded results are in no way comprehensive. However, systems biology provides new methods for heterologous pathway design, particularly the graph-based and constraint-based methods. Based on the databases containing rich metabolism information, they search for and uncover possible metabolic pathways with designated strategy (graph-based method) or algorithm (constraint-based method) and then screen out the optimal pathway to guide the modification of strains. In this paper, we reviewed the databases and algorithms for pathway design, and the applications in metabolic engineering and discussed the strengths and weaknesses of existing algorithms in practical application, hoping to provide a reference for the selection of optimal methods for the design of product synthesis pathway.
Algorithms ; Biosynthetic Pathways ; Metabolic Engineering ; Metabolic Networks and Pathways/genetics* ; Systems Biology

Graph-theory-based pathway analysis is a commonly used method for pathway searching in genome-scale metabolic networks. However, such searching often results in many pathways biologically infeasible due to the presence of currency metabolites (e.g. H⁺, H₂O, CO₂, ATP etc.). Several methods have been proposed to address the problem but up to now there is no well-recognized methods for processing the currency metabolites. In this study, we proposed a new method based on the function of currency metabolites for transferring of functional groups such as phosphate. We processed most currency metabolites as pairs rather than individual metabolites, and ranked the pairs based on their importance in transferring functional groups, in order to make sure at least one main metabolite link exists for any reaction. The whole process can be done automatically by programming. Comparison with existing approaches indicates that more biologically infeasible pathways were removed by our method and the calculated pathways were more reliable, which may facilitate the graph-theory-based pathway design and visualization.
Genome ; Metabolic Networks and Pathways

Objective:The clinical manifestations, types of gene mutations, therapeutic effects and prognostic characteristics of 15 children with cblC type methylmalonic acidemia (MMA) and hydrocephalus were analyzed to improve the clinical understanding of the disease, so as to provide a basis for the treatment of the disease.Methods:From April 2015 to January 2019, 15 patients with MMA and hydrocephalus in Department of Pediatric Surgery, Peking University First Hospital were enrolled, and all gene detection showed clbC type.All the 15 patients underwent ventriculoperitoneal shunt.After surgery, the clinical manifestations and imaging findings were applied as the basis to adjust the pressure of the diverter valve appropriately.Clinical data and gene mutation characteristics of 15 children with cblC type and hydrocephalus were retrospectively analyzed, and the therapeutic effects and prognosis were summarized and analyzed as well.Results:There were 8 males (53.3%) and 7 females (46.7%), aged from 2 to 33 months.All the cases were followed up from 11 to 55 months, without death case and serious postoperative complications of hydroce-phalus.The head circumference of 3 cases (20.0%) was in the normal range, 1 case (6.7%) was greater than the normal range, and 11 cases (73.3%) were less than the normal range.Four patients (26.7%) were transferred to the pediatric intensive care unit after surgery.c.609G>A mutation was the most common in this study, with 7 cases (46.7%) of c. 609G>A homozygous mutation, and 5 cases (33.3%) of c. 609G>A heterozygous mutation.Clinical symptoms of intracranial hypertension were relieved or disappeared.The head circumference progressive enlargement was stopped.The anterior fontanelle tension greatly decreased, all " setting-sun" sign of eyes disappeared, and vision loss and hearing loss were better compared with the pre-operation.Four cases (26.7%) displayed normal intelligence and exercise, and 11 cases (73.3%) were left with mild to severe psychomotor retardation.During the follow-up pe-riod, the head CT showed that the ventricle was remarkably narrowed, and interstitial brain edema obviously improved.Conclusions:Ventriculoperitoneal shunt in the treatment of cblC type MMA with hydrocephalus has positive effects.The head circumference of most cblC type MMA with hydrocephalus is less than the normal range.c.609 G>A is the most common mutation in cblC type MMA with hydrocephalus.Perioperative " metabolic crisis" can result in serious complications.

Objective:To explore the action mechanism of suppressing expression of mitogen- activated protein kinase 14（MAPK14）to alleviate glutamate excitatory toxicity and its neuronal protection effect.Methods:Lentivirus-mediated MAPK14 interference vector was synthetized by Shanghai Jikai Gene Chemical Technology Co.，Ltd. Astrocytes were obtained from SD rats 48 hours after birth，which were cultured in vitro and transfected by lentivirus-mediated transfection. According to the random number table，the cells were divided into three groups：（1）un-transfected group（normal group）with normal astrocytes and the cells were cultured in regular medium composed of Dulbecco's?modified Eagle's?medium（DMEM）；（2）negative control group with astrocytes transfected by MAPK14 no-loaded interference vector；（3）lentivirus transfected group with astrocytes transfected by MAPK14 interference vector. Seventy-two hours after transfection，astrocytes were co-cultured with neurons for 48 hours，and then they were cultured in a medium containing glutamate for 2 hours. The detection indexes included the optimal multiplicity of infection（MOI）value for astrocytes transfected by lentivirus vector，mRNA levels of MAPK14 and glial glutamate transporter 1（GLT-1）detected by rPCR 72 hours after transfection，protein levels of MAPK14 and GLT-1 detected by Western blot 72 hours after transfection，level of lactate dehydrogenase（LDH）and mortality of neurons measured by spectrophotometry and flow cytometry 2 hours after culturing in the medium with glutamate. Results:（1）The optimal MOI value for lentivirus transfecting astrocytes was 30，and astrocytes grew well after transfection.（2）Seventy-two after transfection，the mRNA level of MAPK14 in lentivirus transfected group（0.005 7±0.000 6）was significantly decreased as compared with un-transfected group（0.013 1±0.001 1）and negative control group（0.013 9±0.001 0）（ P<0.01），the mRNA level of GLT-1 in lentivirus transfected group（0.009 1±0.001 2）was not significantly changed as compared with un-transfected group（0.008 7±0.000 3）and negative control group（0.008 9±0.001 1）（ P>0.05）.（3）Seventy-two hours after transfection，the protein level of MAPK14 in lentivirus transfected group（0.29±0.04）was significantly decreased as compared with non-transfected group（0.61±0.05）and negative control group（0.63±0.01）（ P<0.01），the protein level of GLT-1 in lentivirus transfected group（0.73±0.06）was significantly increased as compared with un-transfected group（0.20±0.03）and negative control group（0.23±0.09）（ P<0.01）.（4）After astrocytes were co-cultured with neurons and subsequently cultured in the medium containing glutamate for 2 hours，the level of LDH in lentivirus transfected group［（109.67±2.40）U/L］was significantly lower than that in un-transfected group［（141.52±3.88）U/L］and negative control group［（141.29±3.61）U/L］（ P<0.01）. The mortality of neurons in lentivirus transfected group［（38.72±0.26）%］was significantly lower than that in un-transfected group［（52.94±1.36）%］and negative control group［（54.30±1.23）%］（ P<0.01）. Conclusions:The transfection with lentivirus-mediated MAPK14 interference vector can increase expression of GLT-1 in astrocytes to increase glutamate re-uptake and relieve the glutamate excitatory toxicity in neurons，which may provide a new experimental basis for future use of astrocyte gene regulation to alleviate neuronal injury caused by glutamate excitatory toxicity after traumatic brain injury.

Objective:To explore the clinical value of auto-tube voltage controlled contrast medium injection based on 3rd generation dual source CT coronary angiography.Methods:Patients with suspected coronary heart disease were prospectively enrolled from March to December, 2019 at Shandong Provincial Hospital and coronary CT angiography (CCTA) images were acquired from 220 patients, including 107 male, 113 female, aged from 34 to 82 years. Patients were divided into experimental and control groups with the random number table. In experimental group (113 patients), automatic tube voltage selection technology was used, the contrast agent dosage was set according to tube voltage. The injection time was 10 s; In control group (107 patients), tube voltage and contrast agent dosage were set according to weights. The injection time was 12 s. Images were acquired by ECG gating using the 3rd generation dual source CT (DSCT) with intravenous injection of 350 mg/L contrast medium, followed up with saline of the same dose. Interclass correlation coefficient (ICC) was used to evaluate the individual bias of raters. The rank sum test was used to evaluate the group-level differences of subjective image quality and contrast agent dosage. The t-test was used to evaluate the group-level differences of objective image quality and effective radiation dose (ED). Results:The noise of aortic root in the two groups were (27±4), (26±5) HU, respectively, with no statistical difference ( t=1.017, P=0.284). All ICC values were more than 0.5 indicating good correlation batween 2 raters. The objective image quality score was no significant differences( P>0.05). The subjective image quality scores of the two groups were 1.15±0.10 and 1.18±0.12, respectively, with no statistical difference (Z=-0.231, P=0.818). The ED value (2.2±0.6) mSv of experimental group was statistically lower than that of control group (4.6±1.8) mSv ( t=-13.107, P<0.001); the contrast dosage (35±7) ml of experimental group was statistically lower than that of control group（46±6）ml ( t=-8.699, P<0.001). Conclusions:The novel scanning protocol with auto-tube voltage based contrast agent setting is more convenient and practical with reduced radiation dose and contrast dose, while maintaining image quality.

Objective:To evaluate the role of the nuclear factor E2-related factor 2 (Nrf2) signaling pathway in hydrogen sulfide (H 2S)-induced inhibition of inflammatory responses in the brain tissues of mice with sepsis-associated encephalopathy (SAE). Methods:Fifty-four wild-type C57BL/6J mice and thirty-six Nrf2 -/-C57BL/6J mice, weighing 20-25 g, were divided into 5 groups ( n=18 each) using a random number table method: wild-type sham operation group (wild-type Sham group), wild-type SAE group, wild-type SAE+ NaHS group, Nrf2 -/-SAE group, and Nrf2 -/-SAE+ NaHS group.After the model of SAE was established by cecal ligation and puncture in anesthetized mice.NaHS 50 μmol/kg was intraperitoneally injected at 3 h after the model was successfully established.The mice were sacrificed at 24 h after surgery, and brain tissues were obtained for examination of the phathological changes and for determination of the number of viable neurons, the expression of NLRP3 (by Western blot), contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay), and percentage of Iba-1 + CD86 + , Iba-1 + CD206 + and Iba-1 + cells (by flow cytometry). Results:Compared with wild-type Sham group, NLRP3 expression was significantly up-regulated, contents of TNF-α, IL-1β and IL-6 and percentage of Iba-1 + CD86 + and Iba-1 + cells were increased, and the percentage of Iba-1 + CD206 + cells and neuron survival rate were decreased in wild-type SAE group ( P<0.05). Compared with wild-type SAE group, NLRP3 expression was significantly down-regulated, contents of TNF-α, IL-1β and IL-6, percentage of Iba-1 + and Iba-1 + CD86 + and neuron survival rate were decreased, and the percentage of Iba-1 + CD206 + cells was increased in wild-type SAE+ NaHS group ( P<0.05). There was no significant difference in each parameter between Nrf2 -/-SAE group and Nrf2 -/-SAE+ NaHS group ( P>0.05). Compared with wild-type SAE+ NaHS group, NLRP3 expression was significantly up-regulated, the percentage of Iba-1 + and Iba-1 + CD86 + and contents of TNF-α, IL-1β and IL-6 were increased, and the percentage of Iba-1 + CD86 + cells and neuron survival rate were decreased in Nrf2 -/-SAE+ NaHS group ( P<0.05). Conclusion:Nrf2 signaling pathway is involved in H 2S-induced inhibition of inflammatory responses in the brain tissues of mice with SAE.

Objectives: To establish a geographic information application system for analyzing the spatial and temporal distribution of major infectious diseases in various regions of the world and to assess the risk of importation of those diseases, to China. Methods: We collected and integrated the following information on: 1) outbreaks and areas of epidemics of major infectious diseases in the world from 2000 to 2017, 2) cases of infectious diseases in arriving travelers through active surveillance at international entry-exit ports in mainland China from 2014 to 2016, 3) numbers of annual global international flights and travelers in the country. With the above information, a global space-time distribution database on major infectious diseases was then established, using the technology related to the system. Models regarding technologies on time-space analysis, probabilistic risk assessment and geographic information visualization, were applied to establish a geographic information system on risk assessment of infectious diseases that imported to China. Results: Through integration of information on outbreaks and epidemic areas of 60 major infectious diseases in 220 countries and regions around the world, as well as 42 kinds of infectious diseases identified among the international arrivals in mainland China, a system was then developed. Information on the distribution of major infectious diseases and their potential risks in the worldwide various regions, characteristics of spectrum and disease burden of infectious diseases imported to each province of mainland China were displayed. Thus, risks on importing infectious diseases in each province via air way were able to be evaluated and simulated by the probabilistic risk assessment model, under the information on specific kind of infectious disease, outside China. Conclusion Geographic Information System on Risk Assessment Regarding Infectious Diseases Imported to China provides basic data for epidemiological reconnaissance and assessment on risks of importing infectious diseases outside China, thus would be helpful for the improvement of strategies on surveillance, prevention and control regarding the importing infectious diseases, in China.