Kinetic model analysis is a useful tool for understanding the regulation and control of cellular metabolism and thus offering a guideline for rational design of high efficiency cell factory. Based on previously published models and experimental measurement of enzyme kinetics data, we developed a kinetic model for the threonine biosynthesis pathway in Escherichia coli. This model integrates the central pathways that produce precursors, ATP and reducing power with the threonine biosynthesis pathway from aspartate. In contrast to the previous models, we considered the energy and reducing power balance rather than artificially set their concentrations. Metabolic control analysis of the model showed that enzymes PTS, G6PDH, HDH etc. have great flux control coefficients on the threonine biosynthesis flux. This indicates higher threonine synthesis flux could be achieved by overexpressing these enzymes.
Escherichia coli ; metabolism ; Industrial Microbiology ; Kinetics ; Metabolic Networks and Pathways ; Models, Biological ; Threonine ; biosynthesis

Objective To explore the effect of puncture the left or right branch of portal vein on the incidence of postoperative hepatic encephalopathy in transjugular intrahepatic portosystemic shunt (TIPS). Methods A literature search was conducted through investigating PubMed, Cochrane Library, CNKI digital library and Wanfang databases. Randomized controlled trials and cohort studies related to the effect of puncture the left or right branch of portal vein on the incidence of postoperative hepatic encephalopathy in TIPS were included in this review. According to the methods for Cochrane systematic review, the data were extracted, the quality of the literatures was evaluated, statistical analysis was conducted and the data were analyzed with RevMan 5.0. Results One randomized controlled trial and four cohort studies, including 552 patients with liver cirrhosis received TIPS, were finally included in this review. Random-effects model meta-analysis showed that puncture of the left branch of portal vein in TIPS caused lower incidence of postoperative hepatic encephalopathy than puncture of the right branch of portal vein (RR=0.51, 95%CI was 0.39 to 0.66, P<0.01). Conclusion Puncture of the left branch of portal vein in TIPS can significantly reduce the incidence of postoperative hepatic encephalopathy in comparison with puncture of the right branch of portal vein.

Objectives To study the value of CT and MRI in diagnosing focal nodular hyperplasia (FNH).Methods The CT and MRI findings of 16 patients with FNH confirmed histopathologically were analyzed retrospectively.Both plain and dynamic enhanced CT scannings were performed in all the patients.Plain and dynamic enhanced MRI were carried out in 9 patients.Results (1) There were 16 patients with 19 lesions,and 8 lesions were in the left lobe,5 lesions in the right lobe,4 lesions between the left/right lobes and 2 lesions in the caudate lobe.The morphology of the lesions showed 15 lesions to have clear boundaries and 4 lesions to have fuzzy boundaries.The tumor diameters varied from 2.2 to 9.6 cm,(average 4.3 cm).(2) Sixteen patients underwent CT examination.On plain CT,the lesions were isotonic (n＝ 5),or slightly low-density (n=11).In 7 lesions,there was a slit-like,stellate-shaped low density central scar.Nine patients underwent MRI examination.On T2WI,6 lesions showed slightly higher signal while the remaining 3 lesions showed iso-signal.On T1WI,4 lesions showed slightly lower signal,3 lesions showed iso-signal and 2 lesions showed slightly higher signal while in 1 lesion the local signal showed reduction in anti-phase 1.A central scar was seen in 6 lesions which showed high signal on T2WI,and low signal on T1WI.(3) Enhanced CT: 15 lesions were significantly enhanced and 1 lesion showed mild enhancement at the arterial phase.For the patients with mild enhancement,the scar in the center of the lesion showed no enhancement.In all lesions,the central scar did not enhance.In 5 lesions,enhancements of thickened and torturous arteries were seen.In all the lesions with enhancement,the enhancement was reduced at the portal venous phase,with 12 lesions showing slightly higher density,3 lesions isodensity and 1 lesion low-density.Three lesions showed mild enhancement of the central scar.All the substantial parts of the lesions with enhancement declined at the delay phase,with 3 lesions showing slightly higher density,9 lesions of isodensity and 4 lesions slightly low density.In 7 lesions with central scar delayed enhancement,they showed slightly higher density.Nine patients underwent MRI enhancement and the enhancement characteristics were similar to CT,but the arterial phase magnitude was higher than that of CT.In 4 lesions,the central scar began to enhance at the portal venous phase,while 6 lesions continued to enhance,thus showing slightly higher signal at the delay phase.In a large lesion,there was persistent delayed enhancement in the capsule.(4) On DWI,6 lesions showed inhomogeneous,slightly hyperintensity with the center showing a slit-like low signal area.Three lesions showed iso-signal.The ADC values of the lesions were (1.31±0.08)× 10-3 mm2/s,and the normal liver parenchyma were (1.22± 0.14)× 10-3 mm2/s,(difference not statistically significant).Conclusions CT and MRI using plain and dynamic enhanced scans could show fully and accurately the pathological features and the characteristics of blood supply of FNH.The characteristic signs on both CT and MRI make an accurate diagnosis of FNH.MRI when compared with CT was slightly better.A combined use of both CT and MRI has an important value in the diagnosis of FNH.

Objective　To study the effect of epidermal growt h factor receptor(EGFR) on the development and progress of thymoma. Me thods Expression of EGFR was detected by immunohistochemical stain in t he tissues of 11 cases of normal thymus and 29 cases of thymoma. Result s　 The positive expression of EGFR was 75.9%(22/29) in thymomas and 18.2%(2/11) in normal thymus. The difference was significant(P<0.01). The positive rate of EGFR was higher in invasive thymomas than in non-invasive ones (P<0.01). T he positive rate of EGFR increased with Masaoka stage with a significant increm ent in Ⅲ-Ⅳ stage compared with I stage (P<0.01). EGFR was strongly expre ssed in 5 cases of invasive thymomas, in which recurrence or metastasis occurred in 3 during the follow-up period after operation. But there was no statistical correlation with whether complicated with myasthenia gravis (MG) and histolog ical type. Conclusion　EGFR might be related to the tumori genesis and development of thymoma. There is high risk of recurrence and metast asis in case of EGFR over-expression and radiotherapy, chemotherapy and follow up should be enhanced.

Objective To explore the clinicalpathological characteristics of Lynch syndrome associated ovarian cancer.Methods Totally 260 cases ovarian cancer patients were admitted to Tianjin Medical University General Hospital during Jan.2004 and Jan.2011,among which 10 patients( LS group) belonged to Lynch syndrome associated ovarian cancer according to Amsterdam Ⅱ criteria.One hundred ovarian cancer patients without any family cancer history were enrolled randomizely as control group (sporadic group).Results Lynch syndrome associated ovarian cancer accounted for 3.8％ ( 10/260),the incidence rate of ovarian cancer for female family members of Lynch syndrome was 8.7％ ( 10/115 ).Mean age at time of diagnosis in LS group was (46 ±7) years,significantly earlier than that in sporadic group [ (56 ±11 ) years,P ＜ 0.05 ].There was no statistical difference between two groups in histological type or International Federation of Gynecology and Obstetrics ( FIGO ) stage ( P ＞ 0.05 ).Most of the tissue differentiation in LS group were well or moderate differentiated,there was statistical difference between the two groups(9/10 vs.55％,P ＜0.05).The 3-year and 5-year survival rate in LS group were 87.5％ and 52.5％respectively,compared with 55.4％and 22.7％ in sporadic group(all P＜0.05).Conclusion Compared with sporadic ovarian cancer,Lynch syndrome associated ovarian cancer is more likely present as the clinicalpathological characteristics of early age of onset,serous adenocarcinoma,lower grade and better prognosis.

OBJECTIVETo evaluate the efficacy and safety of testosterone undecanoate (TU) in the treatment of late-onset hypogonadism (LOH) by meta-analysis.

METHODSWe searched Pubmed (until April 1, 2014), Embase (until March 28, 2014), Cochrane Library (until April 17, 2014), CBM (from January 1, 2001 to February 2, 2014), CNKI (from January 1, 2001 to February 2, 2014), Wanfang Database (from January 1, 2000 to February 2, 2014), and VIP Database (from January 1, 2000 to Febru ary 2, 2014) for randomized controlled trials of TU for the treatment of LOH. We evaluated the quality of the identified literature and performed meta-analysis on the included studies using the Rveman5. 2 software.

RESULTSTotally, 14 studies were included after screening, which involved 1 686 cases. Compared with the placebo and blank control groups, TU treatment significantly increased the levels of serum total testosterone (SMD = 6.22, 95% CI 3.99 to 8.45, P < 0.05) and serum free testosterone (SMD = 4.35, 95% CI 1.86 to 6. 85, P < 0.05) but decreased the contents of luteinizing hormone (WMD = -2.23, 95% CI -4.03 to -0.42, P < 0.05), sex hormone binding globulin (WMD = 2.00, 95% CI 1.38 to 2.63, P < 0.05). TU also remarkably reduced the scores of Partial Androgen Deficiency of the Aging Males (WMD = -9.49, 95% CI -12.96 to -6.03, P < 0.05) and Aging Males Symptoms rating scale (WMD = -2.76, 95% CI -4.85 to -0.66, P <0.05) but increased the hemoglobin level (SMD = 2.35, 95% CI 0.29 to 4.41, P < 0.05) and packed-cell volume (SMD = 4.35, 95% CI 1.36 to 7.33, P < 0.05). However, no significant changes were shown in aspertate aminotransferase, alanine transaminase, prostate-specific antigen, or prostate volume after TU treatment (P > 0.05).

CONCLUSIONTU could significantly increase the serum testosterone level and improve the clinical symptoms of LOH patients without inducing serious adverse reactions. However, due to the limited number and relatively low quality of the included studies, the above conclusion could be cautiously applied to clinical practice.

Androgens ; therapeutic use ; Hemoglobin A ; metabolism ; Humans ; Hypogonadism ; blood ; drug therapy ; Luteinizing Hormone ; blood ; Male ; Prostate-Specific Antigen ; Randomized Controlled Trials as Topic ; Sex Hormone-Binding Globulin ; metabolism ; Testosterone ; adverse effects ; analogs & derivatives ; blood ; pharmacology

Objective To approach a semi-quantitative diagnostic criteria of neonatal hypoxic-ischemic encephalopathy(HIE) by comprehensive scoring, including history, clinical manifestation and laboratory data,which can be used for early diagnosis,severity grading and the institution of therapy.Methods We analyzed history, clinical manifestation and some parameters of laboratory data,and established criteria for scoring and grading,and compared this grading with the grading determined by clinical data and follow-up,which brought forward a semi-quantitative diagnostic criteria, and applied this criteria to other 41 patients with HIE to test its reliability.Results The grading criteria were established as the following:if total score ≥20.0,the patient was graded as severe one;total score between 10.5-19.5, moderate one; between 5.5-10.0,mild one;≤5.0,non-HIE one. The scoring system was used in other 41 patients with HIE,the specificity and sensitivity were 100% and 96 .9%,97.2% and 100%,100% and 100%, respectively.Conclusions For severe HIE cases who are not permitted to receive compated tomography(CT) examination or no CT can be used, this scoring system can be used to diagnoze HIE and grade the severity. This method is simple and easy to perform.Both specificity and sensitivity are high for diagnosis and severity judgment of HIE.

Objective To analyze the characteristics of TCM syndromes of children abnormal sweating;To investigate the correlation between diseases and primary and secondary syndromes. Methods Through a multi-center epidemiology investigation, 400 cases were collected to statistically analyze the five TCM syndromes of children abnormal sweating, and characteristics of each syndrome were analyzed. Results In the 400 cases of children abnormal sweating, there were 129 cases (32.25%) of dysfunction of lung-wei pattern, 50 cases (12.50%) of nutrient qi and defensive qi discordance, 84 cases (21.00%) of qi and yin deficiency pattern, 57 cases (14.25%) of dampness heat forced steamed pattern, and 80 cases (20.00%) of qi and yang deficiency pattern. Spontaneous sweating and night sweating were found in the four patterns besides qi and yin deficiency pattern, and night sweating can be mainly found in qi and yin deficiency. Each type is consistent in the syndrome differentiation and cluster analysis. Conclusion Spontaneous sweating and night sweating, each has the certification of yin and yang. Spontaneous sweating can be caused by yin deficiency while night sweating can be caused by yang deficiency. Each pattern of children abnormal sweating has its own syndrome characteristic, which can provide the basis for clinical diagnosis and treatment.

Objective To explore the curative effects of mesenchymal stem cells(MSC)that overexpress in murine type 1 diabetes nephropathy (DN).Methods Mice were randomly divided into normal control(NC) group,DN group,C3-treated group,C3-MIGR1-treated group and C3-MIGR1-ICAM-1-treated group.Mice were given streptozotocin until the DN model was set up.The murine DN model was treated with murine MSC(C3H10T1/2),transfection empty vector of murine MSCs(C3H10T1/2-MIGR1/MSC) and murine MSCs (C3H10T1/2-ICAM-1/MSC)that overexpressed ICAM-1.After transplantation, the pathological features of kidneys were observed by Masson staining and the number of homing MSC cells to the kidney was calculated on days 1,3,7 by frozen section, while qPCR was used to analyze the expression of signaling molecules for collagen1, TGF-β1 and SMAD2 after treatment with various MSCs.Results Compared with DN group, the renal fibrosis treated with MSCs overexpressing ICAM-1 was significantly decreased by Masson staining.Three and seven days after transplant, the homing cells of MSC in different groups displayed no difference using tissue freezing section method.Furthermore, TGF-β1/SMAD signaling was lowly activated after the treatment with MSCs that overexpressed ICAM-1 compared with model mice(P<0.01).Conclusion MSCs that overexpress ICAM-1 can protect kidneys in the DN model.

ObjectiveTo evaluate the clinical effectiveness of posterolateral autograft bone graft fusion transpedicular screw system internal fixation and anterior debridement in the treatment of dorsal and lumber spinal tuberculosis. MethodsFrom March 1996 to July 2000,posterolateral autograft bone graft fusion transpedicular screw system internal fixation and anterior debridement procedures were used in 62 patients suffering from dorsal and lumber spinal tuberculosis in our department,48 of them were involved in a longitudinal study follow-up for a mean of 3.6(1.5-5.5)years postoperatively. ResultsAll patients showed successful posterolateral bone graft fusion. Among 38 cases of Pott's paraplegia, 30 were completely recovered,5 were partly recovered,the rate of recovery was 92.1%. The average immediate postoperative correction of kyphosis angle was 29.1°,the average loss of correction was only 3.2°at final follow-up.ConclusionsPosterolateral autograft bone graft fusion transpedicular screw system internal fixation and anterior debridement procedure were found helpful in strengthening the stability of the spine in dorsal and lumber spinal tuberculosis, providing successful interbody fusion and recovery of Pott's paraplegia, correcting the kyphosis, and preventing progression of kyphosis.