Clinical characteristics and prognosis of patients with myocardial infarction with non-obstructive coronary arteries / 沈阳医学院学报

Objective:To investigate the clinical characteristics of patients with myocardial infarction with non-obstructive coronary arteries(MINOCA)and the risk factors of major adverse cardiovascular events(MACE)within 1 year of follow-up.Methods:A total of 1 866 patients who met the diagnosis of acute myocardial infarction and underwent coronary angiography in the Department of Cardiovascular Medicine of our hospital from Sep 2018 to Sep 2021 were selected.According to the results of coronary angiography,the patients were divided into MINOCA group and myocardial infarction with obstructive coronary artery disease(MI-CAD)group.The clinical characteristics and the occurrence of MACE in the two groups were compared.According to the occurrence of MACE,patients in MINOCA group were divided into MACE group and non-MACE group.Binary logistic regression analysis was used to explore the risk factors for MACE in MINOCA patients.Results:The age of patients in MINOCA group was lower than that in MI-CAD group,and more patients were female(P＜0.05).The risk factors of cardiovascular diseases in MINOCA group were less than those in MI-CAD group(P＜0.05).Some indexes of laboratory were lower than those in MI-CAD group(P＜0.05).Left ventricular ejection fraction(LVEF)were higher than that in MI-CAD group(P＜0.05).Left ventricular end-diastolic inner diameter(LVEDD)was lower than that in MI-CAD group,and the proportion of patients with abnormal ventricular wall motion and high cardiac function grade was lower than that in MI-CAD group,and the difference was statistically significant(P＜0.05).The 1-year follow-up showed no significant difference in the incidence of MACE between the two groups(P=0.115).Binary logistic regression analysis showed that smoking(OR=13.095,95%CI:1.799-7.398)and low LVEF(OR=0.036,95%CI:0.012-0.679)were independent risk factors for MACE in MIONCA patients.Conclusions:MINOCA patients are more common in women,with lower age and fewer cardiovascular risk factors,but the incidence of MACE is not less than that of MI-CAD patients.Smoking and low LVEF are independent risk factors for MACE in MINOCA patients.

Differential effects of hypoxia and oxidative stress on paracrine of mesenchymal stem cells from different sources / 中国组织工程研究

BACKGROUND:The biological behavior of mesenchymal stem cells is influenced by the survival microenvironment.Pre-treatment of the microenvironment is an important means of regulating the function of mesenchymal stem cells. OBJECTIVE:To compare the differences in paracrine function of umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells under oxidative stress and hypoxia,and to provide a theoretical basis for selecting appropriate pretreatment of mesenchymal stem cells to treat different diseases. METHODS:Umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells were cultured by H2O2 or O2 oxygen,respectively,and cell morphology,proliferation,viability and paracrine factor expression were examined. RESULTS AND CONCLUSION:(1)The expression levels of brain-derived neurotrophic factor and transforming growth factor-β were higher in umbilical cord mesenchymal stem cells than in adipose mesenchymal stem cells under a normal culture environment,while the expressions of stromal cell-derived factor-1α and tumor necrosis factor stimulating factor-6 in the adipose mesenchymal stem cells were significantly higher than those in the umbilical cord mesenchymal stem cells.(2)There was no significant difference in the effect of low and moderate levels(≤100 μmol/L)of H2O2 on the viability of the two mesenchymal stem cells.However,increasing the H2O2 concentration from 50 μmol/L to 100 μmol/L resulted in a distinct increase in vascular endothelial growth factor expression in umbilical cord mesenchymal stem cells.The expression of basic fibroblast growth factor,vascular endothelial growth factor,stromal cell-derived factor-1α and interleukin-10 in adipose mesenchymal stem cells was greatly increased by increasing H2O2 concentration in this range.(3)1%O2 hypoxia promoted mesenchymal stem cell proliferation.After 24 hours of culture in 1%O2,gene expression levels were elevated in both mesenchymal stem cells,but the expression levels of vascular endothelial growth factor,interleukin-10 and tumor necrosis factor stimulating factor-6 were significantly higher in adipose mesenchymal stem cells than in umbilical cord mesenchymal stem cells.(4)It is concluded that hypoxia and oxidative stress preconditioning enhances the paracrine function of mesenchymal stem cells.However,mesenchymal stem cells respond differently to hypoxia and oxidative stress.Treating diseases can choose suitable mesenchymal stem cells for appropriate pretreatment to further enhance their therapeutic potential.

Regulatory effect of TRPC3 on the biological behavior of retina in OIR mice and human retinal endothelial cells / 中华实验眼科杂志

Objective:To investigate the regulatory effect of transient receptor potential cation channel subfamily C member 3 (TRPC3) on the retina in oxygen-induced retinopathy (OIR) mice and biological behavior of human retinal vascular endothelial cells (HREC).Methods:A total of 32 healthy SPF grade 7-day-old C57BL/6 mice were selected and randomly divided into a control group and an OIR group by the random number table method, with 16 mice in each group.The control group received no special treatment, and the OIR model was established in the OIR group.On postnatal day 17 (PN17), the success of the model establishment was verified by immunofluorescence staining of the retinal patch.The in vitro cultured HREC were divided into a normal control group, a transfection reagent group, and a si-TRPC3 group.The normal control group received no special treatment, while the transfection reagent group and the si-TRPC3 group were transfected with transfection reagent or transfection reagent + si-TRPC3.The relative expression of TRPC3 mRNA was detected by real-time quantitative fluorescence PCR.The relative expressions of TRPC3, transcription factor NF-E2 related factor (Nrf2), and superoxide dismutase (SOD) proteins were determined by Western blot.HREC were further divided into a normal control group, a vascular endothelial growth factor (VEGF) group, a si-TRPC3 group, and a Pyr3 (TRPC3 channel inhibitor) group, which were cultured in complete medium, medium containing 20 ng/ml VEGF recombinant protein, medium containing 20 ng/ml VEGF recombinant protein (si-TRPC3 transfection for 72 hours), and medium containing 20 ng/ml VEGF recombinant protein+ 1 μmol/L Pyr3 for 48 hours, respectively.The proliferation ability of HREC was detected using cell counting kit 8 (CCK-8). The horizontal and vertical migration ability of cells were detected by cell scratch assay and transwell assay, respectively.This study followed the 3R principles of animal welfare and was approved by the Ethics Committee of Hebei Eye Hospital (No.2023LW04). Results:Pathological neovascular clusters with strong fluorescent staining appeared in the retina of OIR mice on PN17.The relative expressions of TRPC3 mRNA and protein in the retina of OIR mice were 2.057±0.244 and 1.517±0.290, respectively, significantly higher than 0.983±0.033 and 0.874±0.052 of control group ( t=6.165, 3.094; both at P<0.05). The relative expression levels of TRPC3 mRNA and protein were significantly lower, and the relative expression levels of Nrf2 and SOD proteins were higher in the si-TRPC3 group than in the normal control and transfection reagent groups, and the differences were statistically significant (all at P<0.05). The CCK-8 experiment results showed that the cell absorbance value was higher in the VEGF group than in the normal control group, and lower in the si-TRPC3 and Pyr3 groups than in the VEGF group, with statistically significant differences (all at P<0.05). The results of the cell scratch experiment showed that the lateral migration rate of VEGF group cells was higher than that of normal control group, while the lateral migration rate of si-TRPC3 group and Pyr3 group cells was lower than that of VEGF group, and the differences were statistically significant (all at P<0.05). The transwell experiment results showed that the number of stained cells in the VEGF group was higher than that in the normal control group, and the number of stained cells in the si-TRPC3 group and Pyr3 group was lower than that in the VEGF group, with statistically significant differences (all at P<0.05). Conclusions:Hypoxia induces increased TRPC3 expression in OIR mouse retina, and downregulation of TRPC3 inhibits HREC proliferation and migration.The mechanism is related to the activation of the Nrf2-related oxidative stress pathway.

Feasibility of treatment planning for 4D-CT high ventilation functional lung avoided radiotherapy in thoracic cancer / 中华放射医学与防护杂志

Objective:To establish a radiotherapy treatment planning process of high ventilation functional lung avoided (HVFLA) for thoracic tumors based on 4D-CT lung ventilation functional images and determine the treatment planning strategy of HVFLA radiotherapy, and so as to provide support for the clinical trials of HVFLA radiotherapy in thoracic cancer patients.Methods:A deep learning-based 4D-CT lung ventilation functional imaging model was established and integrated into the radiotherapy treatment planning process. Furthermore, ten thoracic cancer patients with 4D-CT simulation positioning were retrospectively enrolled in this study. The established model was used to obtain the 4D-CT lung ventilation functional imaging for each patient. According to the relative value of lung ventilation, the lung ventilation areas are equally segmented into high, medium and low lung ventilation and then imported them into Pinnacle 3 treatment planning system. According to the prescription dose of target and dose constraints of organ at risks (OARs), the clinical and HVFLA treatment plans were designed for each patient using volumetric modulated radiotherapy technique, and each plan should meet the clinical requirements and adding dose constraints of high ventilation functional lung for HVFLA plan. The dosimetric indexes of the target, OARs (lungs, heart and cord) and high functional lung (HFL) were used to evaluated the plan quality. The dosimetric indexes included D2, D98 and mean dose of target, V5, V10, V20, V30 and mean dose of lungs and HFL, V30, V40 and mean dose of heart, and D1 cm 3 of cord. Paired samples t-test was used for statistical analysis of the two groups of plans. Results:The target and OARs of the clinical plan and HVFLA plan meet the clinical requirements. The HVFLA plan resulted in a statistically significant reduction in the mean dose, V5, V10, V20, and V30 of the high functional lung by 1.2 Gy, 5.9%, 4.2%, 2.6%, and 2.3%, respectively ( t=-8.07, 4.02, -6.02, -7.06, -6.77, P<0.05). There was no statistical difference in the dosimetric indexes of lungs, heart and cord. Conclusions:We established the treatment planning process of HVFLA radiotherapy based on 4D-CT lung ventilation functional images. The HVFLA plan can effectively reduce the dose of HFL, while the doses of lungs, heart and cord had no significant difference compared with the clinical plan. The strategy of HVFLA radiotherapy planning is feasible to provide support for the implementation of HVFLA radiotherapy in thoracic cancer patients.

Expression of serological indicators and correlation with severity of coronary artery disease in elderly patients / 中华老年心脑血管病杂志

Objective To investigate the levels of soluble tyrosine kinase-1(sFlt-1)and chemokine C-C ligand 3(CCL3)in serum of patients with coronary heart disease(CHD)and their correlation with the severity of the disease.Methods A total of 230 elderly CHD patients admitted to the De-partment of Cardiovascular Medicine of Xinxiang Central Hospital from November 2020 to No-vember 2022 were collected as the study subjects(CHD group),and according to their Gensini score,they were divided into mild(n=89),moderate(n=95),and severe(n=46)CHD sub-groups.Another 230 healthy individuals who taking physical examination during the same period served as the control group.ELISA was applied to measure serum levels of sFlt-1 and CCL3.ROC curve was plotted to analyze the diagnostic values of serum sFlt-1 and CCL3 levels for CHD.Pear-son correlation analysis was employed to analyze the relationship between serum sFlt-1 and CCL3 levels and the CHD severity.Results The serum levels of sFlt-1 and CCL3 were obviously higher in the CHD group than the control group(121.71±29.80 ng/L vs 98.70±17.57 ng/L,18.22± 5.41 ng/L vs 13.68±3.89 ng/L,P＜0.01).ROC curve analysis showed that the AUC value of the two indicators combined together was significantly greater than that of them alone in diagnosis of CHD(0.886 vs 0.791,0.775,P＜0.01).The serum levels of sFlt-1 and CCL3 were increased along with the severity of the disease and Gensini score when the levels and the score were compared among the mild,moderate and severe subgroups(P＜0.05).Pearson correlation analysis indicated that the serum levels of sFlt-1 and CCL3 were positively correlated with the Gensini score(r=0.420,r=0.479,P＜0.01).Conclusion The levels of serum sFlt-1 and CCL3 are obviously ele-vated in CHD patients,and closely associated with the severity of coronary lesions.

Study on the influencing factors of coronary artery lesions in patients with Kawasaki disease / 重庆医学

Objective To analyze the influencing factors of coronary artery lesions in patients with Ka-wasaki disease(KD)in Xinjiang.Methods A total of 1 500 KD patients who were treated in the First Affilia-ted Hospital of Xinjiang Medical University from December 2020 to December 2022 were selected as the re-search objects.According to whether coronary artery disease occurred,they were divided into two groups.886 patients with coronary artery lesions were included in the experimental group,and 614 patients without coro-nary artery lesions were included in the control group.Univariate and multivariate logistic regression analysis was used to analyze the risk factors of coronary artery lesions.Results The results of logistic regression anal-ysis showed that the duration of fever(＞10 d),high Gensini score,high level of N-terminal pro-brain natri-uretic peptide(NT-proBNP),C-reactive protein(CRP),total cholesterol(TC),low-density lipoprotein cho-lesterol(LDL-C)and triglycerides(TG)may be risk factors for coronary artery lesions(P＜0.05).Conclusion In clinical diagnosis and treatment,targeted intervention should be given as early as possible to prevent the occurrence of coronary artery lesions.

Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

5-Hydroxytryptamine (5-HT) type 3 receptor (5-HT3R) is the only type of ligand-gated ion channel in the 5-HT receptor family. Through the high permeability of Na+, K+, and Ca2+ and activation of subsequent voltage-gated calcium channels (VGCCs), 5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system (CNS). 5-HT3Rs are widely expressed in the medial prefrontal cortex (mPFC), amygdala (AMYG), hippocampus (HIP), periaqueductal gray (PAG), and other brain regions closely associated with anxiety reactions. They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions. 5-HT3Rs mediate the activation of the cholecystokinin (CCK) system in the AMYG, and the γ‍-aminobutyric acid (GABA) "disinhibition" mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons (IINs). In contrast, a 5-HT3R-induced GABA "disinhibition" mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects. 5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG. This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs. However, given the circuit specific modulation of 5-HT3Rs on emotion, systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety, which deeply hinders the current clinical application of 5-HT3R drugs. Therefore, the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

Adaptive evolution of microorganisms based on industrial environmental perturbations / 生物工程学报

The development of synthetic biology has greatly promoted the construction of microbial cell factories, providing an important strategy for green and efficient chemical production. However, the bottleneck of poor tolerance to harsh industrial environments has become the key factor hampering the productivity of microbial cells. Adaptive evolution is an important method to domesticate microorganisms for a certain period by applying targeted selection pressure to obtain desired phenotypic or physiological properties that are adapted to a specific environment. Recently, with the development of technologies such as microfluidics, biosensors, and omics analysis, adaptive evolution has laid the foundation for efficient productivity of microbial cell factories. Herein, we discuss the key technologies of adaptive evolution and their important applications in improvement of environmental tolerance and production efficiency of microbial cell factories. Moreover, we looked forward to the prospects of adaptive evolution to realize industrial production by microbial cell factories.

Biosynthesis of immunosuppressant tacrolimus: a review / 生物工程学报

Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The research on tacrolimus production was mainly focused on biosynthesis methods, within which there are still some bottlenecks. This review summarizes the progress made in tacrolimus biosynthesis via modification of metabolic pathways and control of fermentation process, with the hope to address the technical bottlenecks for tacrolimus biosynthesis and improve tacrolimus production by fermentation engineering and metabolic engineering.

Efficient synthesis of L-methionine by engineering the one carbon module of Escherichia coli / 生物工程学报

L-methionine, also known as L-aminomethane, is one of the eight essential amino acids required by the human body and has important applications in the fields of feed, medicine, and food. In this study, an L-methionine high-yielding strain was constructed using a modular metabolic engineering strategy based on the M2 strain (Escherichia coli W3110 ΔIJAHFEBC/PAM) previously constructed in our laboratory. Firstly, the production of one-carbon module methyl donors was enhanced by overexpression of methylenetetrahydrofolate reductase (methylenetetrahydrofolate reductase, MetF) and screening of hydroxymethyltransferase (GlyA) from different sources, optimizing the one-carbon module. Subsequently, cysteamine lyase (hydroxymethyltransferase, MalY) and cysteine internal transporter gene (fliY) were overexpressed to improve the supply of L-homocysteine and L-cysteine, two precursors of the one-carbon module. The production of L-methionine in shake flask fermentation was increased from 2.8 g/L to 4.05 g/L, and up to 18.26 g/L in a 5 L fermenter. The results indicate that the one carbon module has a significant impact on the biosynthesis of L-methionine, and efficient biosynthesis of L-methionine can be achieved through optimizing the one carbon module. This study may facilitate further improvement of microbial fermentation production of L-methionine.

Short-term clinical observation on the treatment of single-segment lumbar disc herniation and lumbar spinal stenosis by improved transforaminal endoscopic spine system technique with full visual endoscopic foraminoplasty / 中国综合临床

Objective:To investigate the safety and efficacy of the modified transcutaneous endoscopic spine system (TESSYS) with full visual foramen plasty and percutaneous endoscopic discectomy (PTED) in the treatment of lumbar disc herniation and lumbar spinal stenosis.Methods:A case-control study was conducted to analyze the clinical data of 68 patients with single segment lumbar disc herniation and lumbar spinal stenosis treated with visual endoscopic foraminal plasty and modified TESSYS technique and intervertebral foraminal fusion from April 2020 to March 2021. According to the operation method, 38 cases were divided into two groups: pted group (38 cases) and TLIF group (30 cases). Independent sample t-test was used to compare the incision length, bleeding volume, operation time, time to go down and hospital stay between the two groups. Visual analog scale (VAS) scores and Oswestry disability index (ODI) scores were measured repeatedly. The differences between preoperative and postoperative 7 days and 1, 3, 6 months were analyzed and compared by generalized estimation equation. Rank sum test was performed in combination with the modified MacNab standard in the last follow-up. The excellent and good rate was compared between groups χ 2. Test and evaluate the curative effect. Results:The postoperative follow-up was 8.5-14.0 months. The incision length (1.25±0.33) cm, operation time (119.45±14.95), blood loss (24.03±8.62) mL, downtime time (1.42±0.50) d, and hospital stay (3.39±0.55) d in the PTED group were all higher than those in the TLIF group ((14.37±2.91) cm, (140.53±16.16) min, (158.00±51.35) mL, (3.20±0.96) d, (7.33±0.55) d) had obvious advantages ( t values were 24.56, 5.57, 14.13, 9.20, and 29.48, respectively; all P<0.001). The VAS scores and ODI scores of the two groups after operation were significantly improved compared with those before operation (all P<0.001), and with the passage of time, the VAS scores and ODI scores of the two groups of patients from 7 days to 6 months after operation by month were significantly decreased ( P<0.001). However, there was no significant difference between the two groups in VAS score from 1 week to 6 months after operation: P7d=0.997, P1 month=0.139, P3 month=0.057, P6 month=0.539, all P>0.05. There was no significant difference in ODI scores between time points (ODI: P7d=0.278, P1 month=0.442, P3 month=0.963, P6 month=0.278, all P>0.05). There was no significant difference between the two groups in terms of clinical efficacy and excellent and good rate evaluated by modified MacNab criteria at the last follow-up ( Z=0.09, P=0.927; χ 2=0.92, P=0.761). Conclusion:The short-term curative effect of full visual endoscopic foraminal plasty and modified TESSYS technique in the treatment of single level lumbar disc herniation and lumbar spinal stenosis is close to that of classical foraminal interbody fusion, and has certain advantages.

Evaluation of Qi-deficiency Model Based on Urine Non-targeted Metabonomics / 中国实验方剂学杂志

ObjectiveTo evaluate the success of Qi-deficiency model of Balb/C-nu mice established by swimming exhaustion test from the view of biomarkers and metabolic pathways by metabonomics. MethodBalb/C-nu mice were randomly divided into the normal group and Qi-deficiency group， Qi-deficiency model was established by swimming with 5% body weight metal fixed at the tail for 15 consecutive days until exhaustion （nose tip immersion time>5 s）. The urine metabonomics was analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS）， and the mobile phase was acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-1 min， 5%-8%A； 1-4 min， 8%-8.5%A； 4-5 min， 8.5%-12%A； 5-10 min， 12%-40%A； 10-12 min， 40%-100%A； 12-15 min， 100%A）， the flow rate was 0.3 mL·min-1， the injection volume was 10 μL， electrospray ionization （ESI） in positive and negative ion modes was used in MS analysis， the MS data were acquired in full-scan mode from m/z 50-1 000. Principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， human metabolome database （HMDB）， high collision energy ion fragments collected by MSE and tandem MS （MS/MS） ion information were used to identify potential biomarkers. Kyoto Encyclopedia of Genes and Genomes （KEGG） database and MetaboAnalyst 5.0 were used to analyze the corresponding metabolic pathways and pathway enrichment of biomarkers. ResultEndogenous substances in urine of mice in normal group and Qi-deficiency group were obviously separated， and there were 24 biomarkers with significant difference. The metabolic pathways involved in these biomarkers were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism， steroid hormone biosynthesis and tryptophan metabolism. Among them， the metabolic pathways related to energy were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism and steroid hormone biosynthesis. ConclusionThrough the investigation of urine metabonomics， combined with the physical signs， the Qi-deficiency model established by swimming exhaustion test in Balb/C-nu mice is successfully evaluated， and it is also verified that there is a close correlation between Qi-deficiency and energy metabolism.

Evaluation of Qi-deficiency Model Based on Urine Non-targeted Metabonomics / 中国实验方剂学杂志

ObjectiveTo evaluate the success of Qi-deficiency model of Balb/C-nu mice established by swimming exhaustion test from the view of biomarkers and metabolic pathways by metabonomics. MethodBalb/C-nu mice were randomly divided into the normal group and Qi-deficiency group， Qi-deficiency model was established by swimming with 5% body weight metal fixed at the tail for 15 consecutive days until exhaustion （nose tip immersion time>5 s）. The urine metabonomics was analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS）， and the mobile phase was acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-1 min， 5%-8%A； 1-4 min， 8%-8.5%A； 4-5 min， 8.5%-12%A； 5-10 min， 12%-40%A； 10-12 min， 40%-100%A； 12-15 min， 100%A）， the flow rate was 0.3 mL·min-1， the injection volume was 10 μL， electrospray ionization （ESI） in positive and negative ion modes was used in MS analysis， the MS data were acquired in full-scan mode from m/z 50-1 000. Principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， human metabolome database （HMDB）， high collision energy ion fragments collected by MSE and tandem MS （MS/MS） ion information were used to identify potential biomarkers. Kyoto Encyclopedia of Genes and Genomes （KEGG） database and MetaboAnalyst 5.0 were used to analyze the corresponding metabolic pathways and pathway enrichment of biomarkers. ResultEndogenous substances in urine of mice in normal group and Qi-deficiency group were obviously separated， and there were 24 biomarkers with significant difference. The metabolic pathways involved in these biomarkers were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism， steroid hormone biosynthesis and tryptophan metabolism. Among them， the metabolic pathways related to energy were tricarboxylic acid cycle， glycolysis metabolism， amino acid metabolism， fatty acid metabolism， pyrimidine metabolism and steroid hormone biosynthesis. ConclusionThrough the investigation of urine metabonomics， combined with the physical signs， the Qi-deficiency model established by swimming exhaustion test in Balb/C-nu mice is successfully evaluated， and it is also verified that there is a close correlation between Qi-deficiency and energy metabolism.

Construction and application of microbial cell factories for unnatural amino acids / 生物工程学报

Unnatural amino acids are widely used in medicine, pesticide, material, and other industries and the green and efficient synthesis has attracted a lot of attention. In recent years, with the rapid development of synthetic biology, microbial cell factories have become a promising means for biosynthesis of unnatural amino acids. This study reviewed the construction and application of microbial cell factories for unnatural amino acid, including the synthetic pathway reconstruction, design/modification of key enzymes and their coordinated regulation with precursors, blocking of competitive alternative pathways, and construction of cofactor circulation systems. Meanwhile, on the basis of the new principles for designing the microbial cell factories, new biosynthetic pathways adapted to cells and the production environment, as well as new biomanufacturing system established based on cell adaptive evolution and intelligent fermentation regulation, we looked forward to the further construction and application of microbial cell factories for industrial bio-production.

Advances in the biosynthesis of L-homoserine and its derivatives by metabolic engineering of Escherichia coli / 生物工程学报

L-homoserine and its derivatives (O-succinyl-L-homoserine and O-acetyl-L-homoserine) are precursors for the biosynthesis of L-methionine, and various C4 compounds (isobutanol, γ-butyrolactone, 1, 4-butanediol, 2, 4-dihydroxybutyric acid) and L-phosphinothricin. Therefore, the fermentative production of L-homoserine and its derivatives became the research hotspot in recent years. However, the low fermentation yield and conversion rate, and the unclear regulation mechanism for the biosynthesis of L-homoserine and its derivatives, hamper the development of an efficient production process for L-homoserine and its derivatives. This review summarized the advances in the biosynthesis of L-homoserine and its derivatives by metabolic engineering of Escherichia coli from the aspects of substrate uptake, redirection of carbon flow at the key nodes, recycle of NADPH and export of target products. This review may facilitate subsequent metabolic engineering and biotechnological production of L-homoserine and its derivatives.

Construction of an l-cysteine hyper-producing strain of Escherichia coli based on a balanced carbon and sulfur module strategy / 生物工程学报

l-cysteine is an important sulfur-containing α-amino acid. It exhibits multiple physiological functions with diverse applications in pharmaceutical cosmetics and food industry. Here, a strategy of coordinated gene expression between carbon and sulfur modules in Escherichia coli was proposed and conducted for the production of l-cysteine. Initially, the titer of l-cysteine was improved to (0.38±0.02) g/L from zero by enhancing the biosynthesis of l-serine module (serAf, serB and serCCg) and overexpression of CysB. Then, promotion of l-cysteine transporter, increased assimilation of sulfur, reduction or deletion of l-cysteine and l-serine degradation pathway and enhanced expression of cysEf (encoding serine acetyltransferase) and cysBSt (encoding transcriptional dual regulator CysB) were achieved, resulting in an improved l-cysteine titer (3.82±0.01) g/L. Subsequently, expressions of cysM, nrdH, cysK and cysIJ genes that were involved in sulfur module were regulated synergistically with carbon module combined with utilization of sulfate and thiosulfate, resulting in a strain producing (4.17±0.07) g/L l-cysteine in flask shake and (11.94±0.1) g/L l-cysteine in 2 L bioreactor. Our results indicated that efficient biosynthesis of l-cysteine could be achieved by a proportional supply of sulfur and carbon in vivo. This study would facilitate the commercial bioproduction of l-cysteine.

Predictive value of apolipoprotein B to apolipoprotein A-Ⅰ ratio combined with carotid intima media thickness in acute cerebral infarction / 中风与神经疾病杂志

@#To investigate the value of apolipoprotein B to apolipoprotein AⅠ ratio combined with carotid intimamedia thickness in predicting acute cerebral infarction.Methods Patients with acute large artery atherosclerotic cerebral infarction in the anterior circulation who were hospitalized in the Department of Neurology，The First Affiliated Hospital of Xinjiang Medical University from July 2020 to June 2021 were selected as the case group.Patients with noncardiovascular and cerebrovascular diseases who were hospitalized during the same period were randomly selected as the control group.The clinical data and laboratory results of the two groups were compared，and the risk factors of acute cerebral infarction were analyzed.To explore the predictive value of apolipoprotein B to apolipoprotein AⅠratio combined with carotid intimamedia thickness in the incidence of cerebral infarction.The clinical data and laboratory results of the two groups were compared.The influencing factors of acute cerebral infarction were analyzed by logistic regression.The receiver operating characteristic curve was used to analyze the predictive value of the ratio of apolipoprotein B to apolipoprotein AⅠcombined with carotid intimamedia thickness in the incidence of cerebral infarction.Results The study included 143 patients with acute cerebral infarction and 122 patients with noncardiovascular and cerebrovascular diseases.Multivariate analysis showed that smoking（OR=3.448，95%CI 1.609-7.391），diabetes（OR=2.884，95%CI 1.389-5.989），carotid intimamedia thickness （OR=1.633，95%CI 1.219-2.189），Leukocytes （OR=1.258，95%CI 1.036-1.527），free fatty acids（OR=14.113，95%CI 1.942-102.558），ratio of apolipoprotein B to apolipoprotein AI（OR=10.896，95%CI 2.290-51.846），D Dimer（OR=4.690，95%CI 2.097-10.488），homocysteine（OR=9.594，95%CI 1.112-82.772） were independent risk factors for large atherosclerotic cerebral infarction.The value of the ratio of apolipoprotein B to apolipoprotein AⅠ [JP3]and carotid intimamedia thickness in predicting acute cerebral infarction was analyzed by receiver operating characteristic curve.The results showed that the area under the curve was 0.757（95%CI 0.699-0.816），the best predictive value was 0.466，the sensitivity was 81.8%，and the specificity was 58.2%.Conclusion The ratio of apolipoprotein B to apolipoprotein AⅠ and the carotid intimamedia thickness are related to the atherosclerotic cerebral infarction of the anterior circulation large arteries，and they have a certain value in jointly predicting the incidence of cerebral infarction.

Metabolic engineering of Escherichia coli for L-homoserine production / 生物工程学报

L-Homoserine is a non-essential amino acid that is often used as an important platform compound and additive in industrial production. To improve the production efficiency, a previously constructed L-homoserine producing strain E. coli H0-0 was used as a chassis for further metabolic modification. Firstly, the ppc and pyccgP458S genes were overexpressed to optimize the Kreb's cycle. Subsequently, thrAC1034T and lysCcgC932T were overexpressed to improve the product synthesis, followed by inactivation of iclR gene to reduce the accumulation of by-products. The introduction of three sucrose metabolism genes, scrA, scrB and scrK, enabled E. coli to ferment sucrose. The titer of L-homoserine increased from 3.2 g/L to 11.1 g/L.

Research on Application of Intelligent Tracing System for IVD Reagents Based on Blockchain Technology / 中国医疗器械杂志

In recent years, the IVD industry has developed rapidly based on the increasing market demand, and plays an important role in disease prevention, clinical diagnosis, health monitoring and guiding treatment. Therefore, followed quality and safety issues are highly concerned. The unique advantages of blockchain technology, decentralization, distrust and non-tampering, can write into trusted node data in every link covering production, circulation and usage of IVD reagents, and establish a distributed ledger with full backup, which makes the anti-conterfeiting and traceability for IVD reagents possible. We discuss whole process intelligent tracing system for IVD reagents based on blockchain technology. Through the strong mechanism of pre-supervision and post-punishment, the source of reagents can be traced, quality and responsibility can be investigated, and the medical inspection quality and diagnostic safety can be guarded.

Single Exposure to Cocaine Impairs Reinforcement Learning by Potentiating the Activity of Neurons in the Direct Striatal Pathway in Mice / 神经科学通报·英文版

Plasticity in the glutamatergic synapses on striatal medium spiny neurons (MSNs) is not only essential for behavioral adaptation but also extremely vulnerable to drugs of abuse. Modulation on these synapses by even a single exposure to an addictive drug may interfere with the plasticity required by behavioral learning and thus produce impairment. In the present work, we found that the negative reinforcement learning, escaping mild foot-shocks by correct nose-poking, was impaired by a single in vivo exposure to 20 mg/kg cocaine 24 h before the learning in mice. Either a single exposure to cocaine or reinforcement learning potentiates the glutamatergic synapses on MSNs expressing the striatal dopamine 1 (D1) receptor (D1-MSNs). However, 24 h after the cocaine exposure, the potentiation required for reinforcement learning was disrupted. Specific manipulation of the activity of striatal D1-MSNs in D1-cre mice demonstrated that activation of these MSNs impaired reinforcement learning in normal D1-cre mice, but inhibition of these neurons reversed the reinforcement learning impairment induced by cocaine. The results suggest that cocaine potentiates the activity of direct pathway neurons in the dorsomedial striatum and this potentiation might disrupt the potentiation produced during and required for reinforcement learning.