Since its establishment 30 years ago, the discipline of metabolic engineering has developed rapidly based on its deep integration with molecular biology, systems biology and synthetic biology successively, which has greatly contributed to advancing and upgrading biotechnology industry. This review firstly analyzes the current status of academic research and China's competence in the area of metabolic engineering according to the data of papers published in SCI-indexed journals in the past 30 years. Subsequently, the article summarizes the development of systems biology methods and enabling technologies of synthetic biology and their applications in metabolic engineering in the past 10 years. Finally, the major challenges and future perspectives for the development of metabolic engineering are briefly discussed.
Biotechnology ; Industry ; Metabolic Engineering ; Synthetic Biology ; Systems Biology

Objective:To analyze the characteristics and prognosis of hearing loss in children with bacterial meningitis.Methods:This was a single-center retrospective cohort study. Patients diagnosed with bacterial meningitis who were hospitalized in Beijing Children′s Hospital between 2010 and 2016 and older than 28 days and younger than 18 years at symptom onset were included in this study ( n=573). All clinical information including hearing assessment results during hospitalization were reviewed. All patients with hearing loss were followed up to repeat their hearing test and assess their hearing condition with parents′ evaluation of aural and (or) oral performance of children (PEACH). Patients were grouped according to their hearing assessment results, and Logistic regression analysis was used to analyze the risk factors for hearing loss in patients with bacterial meningitis. Results:Five hundred and seventy-three patients were enrolled in this study, including 347 males and 226 females. The onset age ranged from 29 days to 15.8 years. Two hundred and forty-six patients had identified causative pathogens, among whom 92 cases (37.4%) were pneumococcal meningitis cases. Hearing loss was found in 160 cases (27.9%) during hospitalization, involving 240 ears. Permanent hearing loss was found in 20 cases (16.9%), involving 32 ears. In the patients with permanent hearing loss, 87.5% (28/32) of ears were identified as severe or profound hearing loss during hospitalization. Logistic regression analysis showed that dystonia, the protein concentration level in cerebrospinal fluid>1 g/L, glucose concentration level lower than 1 mmol/L and subdural effusion were independent risk factors for hearing loss ( OR=2.426 (1.450-4.059), 1.865 (1.186-2.932), 1.544 (1.002-2.381) and 1.904 (1.291-2.809)). Conclusions:Hearing loss is a common sequela of bacterial meningitis in children. Most patients have transient hearing loss, but patients with severe or profound hearing impairment have a higher risk of developing permanent hearing loss.

OBJECTIVE: To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use. METHODS: Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r). RESULTS: The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results. CONCLUSIONS In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.
Databases, Pharmaceutical ; Decision Making, Computer-Assisted ; Drug Monitoring ; Drug-Related Side Effects and Adverse Reactions ; HIV Protease Inhibitors ; adverse effects ; pharmacology ; Humans ; Liver ; drug effects ; Lopinavir ; adverse effects ; toxicity ; Models, Statistical ; Reproducibility of Results ; Software ; standards

Objective To investigate the calcification characteristics and biological activity of hepatic alveolar echinococcosis(HAE). Methods Retrospective analysis of 60 patients in the First Affiliated Hospital of Xinjiang Medical University from June 2016 to April 2017 with hydatid positive or surgical pathology confirmed HAE.All patients underwent abdominal CT scan and double-phase enhanced PET-CT examination were confirmed with single lesion.The CT and PET-CT features were analysed,and the maximum standard uptake value (SUVmax) of the focal lesion on the PET-CT was measured. According to the calcification,HAE patients were divided into A,B,C type.Kruskal-Wallis H test was used to compare the difference of SUVmax between lesions of different HAE types. Results Sixty patients with hepatic alveolar echinococcosis were evenly divided into A,B and C by different calcifications.The median SUVmax of A,B and C were 3.41(2.17 to 3.75),7.45(6.77 to 9.01)and 6.67(6.28 to 9.01),respectively.The median SUVmax within three types was statistically significant (χ2=4.429, P<0.05). Conclusion The biological activity of different HAE calcifications is different.

BACKGROUND/AIMS: The relationship between C-peptide levels and gastrointestinal (GI) symptoms in type 2 diabetic patients is not clear. The purpose of this study is to examine the association between fasting C-peptide and GI symptoms of gastroparesis in type 2 diabetic patients. METHODS: We recruited 333 type 2 diabetic patients into the present study. All patients filled out questionnaires of gastroparesis cardinal symptom index (GCSI) to evaluate GI symptoms. Hospital anxiety and depression scale were adopted to define anxiety and depression. Patients with GCSI scores ≥ 1.9 were regarded as having symptoms of gastroparesis. RESULTS: In our study, 71 (21.3%) type 2 diabetic patients had GCSI scores ≥ 1.9. In comparison to patients with scores < 1.9, those with scores ≥ 1.9 had significantly lower fasting c-peptide levels (1.49 ng/mL vs 1.94 ng/mL, P < 0.001), higher prevalence of depression (40.9% vs 18.3%, P < 0.001) and anxiety (28.2% vs 13.0%, P = 0.002). Multivariate logistic regression revealed that fasting C-peptide was still significantly associated with symptoms of gastroparesis (odds ratio, 0.67; 95% confidence intervals, 0.48–0.94; P = 0.021), even after adjustments for age, sex, body mass index, HbA1c, current smoking and drinking status, anxiety, and depression. Furthermore, linear regressions showed that fasting C-peptide was independently and negatively related to GCSI scores (standardized regression coefficient, −0.29; P < 0.001) in patients with at least one GI symptom. CONCLUSION: GI symptoms of diabetic gastroparesis affect approximately 20% of type 2 diabetes patients and are associated with lower fasting C-peptide levels independent of depression and anxiety status.
Anxiety ; Anxiety Disorders ; Body Mass Index ; C-Peptide* ; Depression ; Depressive Disorder ; Diabetes Mellitus ; Drinking ; Fasting* ; Gastroparesis* ; Humans ; Linear Models ; Logistic Models ; Prevalence ; Smoke ; Smoking

[Objective] The present study was to evaluate the association of serum total cholesterol level and prognosis in patients with acute left heart failure and associated mechanisms.[Methods] Sixty-eight patients due to acute episode of left heart failure prospectively enrolled,and baseline data and biochemical parameters were collected.After discharge,patients were follow-up for 1 month and they were divided into two groups (with and without cardiovascular events).Differences between groups were evaluated and the association of serum total cholesterol level and cardiovascular events were analyzed by logistic regression analysis.[Results] The mean age was 57.3 ± 12.6 years old and 52 cases were male patients accounting for 76.5 ％.Among these patients,46 had a diagnosis of coronary heart disease (67.6 ％),10 rheumatic heart disease (14.7 ％),12 dilated cardiomyopathy (17.7％),38hypertension (55.9％) and 24 diabetes mellitus (35.3％).After 1 month's follow up,39 patients (57.4％) had experienced cardiovascular events,36 cases were re-hospitalized,and 3 died from heart failure.Compared to those with cardiovascular events,event free individuals were younger and were less likely smokers (P ＜ 0.05).In addition,event free group had lower serum levels of N-terminal pro-BNP and C-reactive protein (P ＜ 0.05) while serum levels of total cholesterol and albumin were significantly higher (P ＜ 0.05).There was no significant difference in medication between these two groups.After adjusted for age,gender,smoking,systolic blood pressure,serum albumin level,diabetes,hypertension and medications,increased total cholesterol level was independently associated with better prognosis with odds ratio of 0.91 (95 ％ confidence interval 0.80-0.96).Further adjusted for C-reactive protein,the association was attenuated to non-significance,with odds ratio of 0.97 (95 ％ confidence interval 0.87-1.09).[Conclusion] Adequate serum total cholesterol level was beneficial for improving short-term cardiovascular outcomes in patients with left heart failure and the potential mechanisms might be related to cholesterol effects on improving nutritional status and anti-inflammation.

Objective: To explore correlation among clinic blood pressure (CBP), ambulatory blood pressure (ABP) and cardiovascular diseases in diabetic populations.Methods: A total of 336 patients complicated with type 2 diabetes mellitus, who received 24h ambulatory blood pressure monitoring, were selected.According to complicated with coronary heart disease or stroke or not, they were divided into cardiovascular disease group (CVD group, n=122) and no cardiovascular disease group (NCVD group, n=214).Blood lipids, blood pressure, CBP and ABP etc.were compared between two groups;according to median of 24h mean SBP (122mmHg), they were divided into <122mmHg group (n=168) and ≥122mmHg group (n=168), incidence of cardiovascular diseases was compared between these two groups.Results: (1) Compared with NCVD group, there were significant rise in age, percentages of smoking and hypertension, and plasma hsCRP level in CVD group (P<0.05 or <0.01);for ambulatory blood pressure,there were significant rise in levels of 24h mean SBP(mSBP) [(119.8±8.7)mmHg vs.(124.4±9.6) mmHg], daytime SBP (dSBP)[(121.4±9.3) mmHg vs.(128.0±10.3) mmHg] and nighttime SBP(nSBP) [(114.4±4.2) mmHg vs.(120.8±4.7) mmHg] in CVD group, P<0.01 all;there was no significant difference in CBP between two groups;(2) compared with <122mmHg group, there were significant rise in percentages of stroke (20.2% vs.25.0%) and total cardiovascular diseases (32.7% vs.39.9%) in ≥122mmHg group, P<0.01 both;(3) Logistic regression analysis indicated that diabetic patients no matter complicated with hypertension or not, 24h mean SBP was always an independent risk factors of diabetic patients complicated cardiovascular diseases (OR=1.83, 1.36, P<0.05 all).Conclusion: ABP is superior to CBP in predicting cardiovascular risk in patients with diabetes, and 24h mean SBP may be a good ABP index to predict cardiovascular risk.

OBJECTIVEThis study aimed to explore the differences of membrane thickness and pressure on the paranasal sinus membrane in goats and analyze their causes. The results can provide theoretical basis and guidance for the issues of the maxillary sinus floor augmentation related to the membrane.

METHODSThe membrane was cut into two sizes from every sinus membrane. The membrane was fixed in formalin to obtain tissue specimens for the membrane thickness study and pressure study. The correlation between the two parameters was then analyzed, and appropriate statistical methods and software were selected.

RESULTSThe top of maxillary sinus, the bottom of maxillary sinus and the frontal sinus membrane thickness were (410.03 ± 65.97), (461.33 ± 91.37), (216.90 ± 46.47) µm. The pressure were (260.08 ± 80.12), (306.90 ± 94.37), (121.72 ± 31.72) kPa. The mean differences of the membrane thickness between the top of the maxillary sinus and the frontal sinus, bottom and frontal, and top and bottom were statistically significant (P < 0.05). The mean differences in membrane pressure were also statistically significant (P < 0.05).

CONCLUSIONThe membrane thickness and pressure of the top and bottom of the maxillary sinus are higher than those of the frontal sinus membrane. However, the thickness and pressure of the bottom membrane are slightly higher than those of the top membrane. Pressure and membrane thickness are positively correlated in the sinus membrane.

Animals ; Goats ; Maxillary Sinus ; Sinus Floor Augmentation ; Software

Objective This study aimed to explore the differences of membrane thickness and pressure on the paranasal sinus membrane in goats and analyze their causes. The results can provide theoretical basis and guidance for the issues of the maxillary sinus floor augmentation related to the membrane. Methods The membrane was cut into two sizes from every sinus membrane. The membrane was fixed in formalin to obtain tissue specimens for the membrane thickness study and pressure study. The correlation between the two parameters was then analyzed, and appropriate statistical methods and software were selected. Results The top of maxillary sinus, the bottom of maxillary sinus and the frontal sinus membrane thickness were (410.03±65.97), (461.33±91.37), (216.90±46.47) μm. The pressure were (260.08±80.12), (306.90±94.37),(121.72±31.72) kPa. The mean differences of the membrane thickness between the top of the maxillary sinus and the frontal sinus, bottom and frontal, and top and bottom were statistically significant (P<0.05). The mean differences in membrane pressure were also statistically significant (P<0.05). Conclusion The membrane thickness and pressure of the top and bottom of the maxillary sinus are higher than those of the frontal sinus membrane. However, the thickness and pressure of the bottom membrane are slightly higher than those of the top membrane. Pressure and membrane thickness are positively correlated in the sinus membrane.

OBJECTIVETo summarize the clinical characteristics and long-term prognosis of herpes simplex virus encephalitis (HSE) in childhood and to analyze genotype of UNC93B1 and TLR3.

METHODData of a total of 30 HSE patients admitted to Beijing Children's Hospital from January 2008 to September 2013 were retrospectively analyzed, the data included clinical manifestations, physical sign, auxiliary examination, therapy and long-term clinical prognosis. The family history obtained during follow-up visit was also analyzed for genetic predisposition. With parents' agreement, the blood specimens of patients were collected in EDTA anticoagulant tubes, the first 2 genetic etiologies UNC93B1 and TLR3 were sequenced, and the genetic susceptibility to HSE in childhood was summarized.

RESULT(1) All the 30 patients (100%) had fever, 28 (93%) had seizure, 25 (83%) had altered state of consciousness, only 11 (37%) had personality changes, and in 8 (73%) appeared at or after 2 weeks of onset . (2) During the long-term follow up, 2 (7%) patients died after discharge, 23 patients (82%) had neurological sequelae, 13 patients (57%) had moderate, severe disability and vegetative state. (3) After sequencing of UNC93B1, and TLR3, one patient was found homozygous for a single-nucleotide substitution at position C.414C>G in exon 4 of UNC93B1 which affected the expression of UNC93B1, and may block or decrease the production of interferon. (4) Six single nucleotide polymorphisms (SNPs) were found in this study, their genotype frequency and gene frequency of Chinese were respectively searched in Genomes Project in NCBI and defined 1 000 genomes group. The genotype frequency of UNC93B1 rs7149 between 1 000 genomes group and HSE group was significantly different (χ² = 55.37, P<0.05). The frequency of CC type and C type was higher in HSE group, both of them had significant difference (χ² = 93.90, P<0.05, OR=61.563; χ² = 134.40, P<0.05, OR=12.491).

CONCLUSIONHSE lacks specific clinical manifestations, the long-term prognosis is poor. One HSE patient carrying a heterozygous mutation in UNC93B1 which may lead to the susceptibility to HSE and had harmful effect on long-term prognosis. The SNP UNC93B1 rs7149 may also have relationship with susceptibility to HSE and the children carrying CC genotype or C gene in this gene site maybe more susceptible to HSE.

Child ; Encephalitis, Herpes Simplex ; diagnosis ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Membrane Transport Proteins ; genetics ; Mutation ; Polymorphism, Single Nucleotide ; Prognosis ; Retrospective Studies ; Toll-Like Receptor 3 ; genetics