Objective:To evaluate the impact of implementing a regional hierarchical medical management model based on the medical internet of things (medical IoT) on the frequency of emergency department visits and hospitalizations, as well as related medical expenses, in patients with chronic obstructive pulmonary disease (COPD).Methods:This retrospective study included COPD patients enrolled in the regional hierarchical medical management system based on Medical IoT across 21 community health service centers in Songjiang District, Shanghai, between July 2017 and May 2018. Utilizing patient data from the year prior to enrollment as the baseline, changes in the number of emergency visits, hospitalizations, and associated medical costs during the first and second years of management were compared. Changes for patients receiving drug treatment were also analyzed.Results:A total of 973 COPD patients were enrolled. The mean age was 75.2±17.0 years, and 64.34% (626/973) were male. Compared to baseline, all COPD patients in the first year of management showed significant reductions: emergency visits decreased by 33.67%, total emergency costs by 45.60%, hospitalizations by 27.15%, and total hospitalization costs by 25.42%. In the second year, reductions were: emergency visits by 28.08%, total emergency costs by 36.10%, hospitalizations by 35.26%, and total hospitalization costs by 18.13% (all P<0.05). Among patients receiving drug therapy, reductions in the first year were: emergency visits by 39.66%, total emergency costs by 47.54%, hospitalizations by 25.19%, and total hospitalization costs by 28.40%. In the second year, reductions were: emergency visits by 46.98%, total emergency costs by 45.99%, hospitalizations by 41.98%, and total hospitalization costs by 24.94% (all P<0.05). No significant differences were observed before and after management for patients without drug treatment. Conclusion:The implementation of the regional hierarchical medical management model based on Medical IoT significantly reduced the frequency of emergency visits and hospitalizations, as well as related costs, for COPD patients.

Objective:To evaluate the impact of implementing a regional hierarchical medical management model based on the medical internet of things (medical IoT) on the frequency of emergency department visits and hospitalizations, as well as related medical expenses, in patients with chronic obstructive pulmonary disease (COPD).Methods:This retrospective study included COPD patients enrolled in the regional hierarchical medical management system based on Medical IoT across 21 community health service centers in Songjiang District, Shanghai, between July 2017 and May 2018. Utilizing patient data from the year prior to enrollment as the baseline, changes in the number of emergency visits, hospitalizations, and associated medical costs during the first and second years of management were compared. Changes for patients receiving drug treatment were also analyzed.Results:A total of 973 COPD patients were enrolled. The mean age was 75.2±17.0 years, and 64.34% (626/973) were male. Compared to baseline, all COPD patients in the first year of management showed significant reductions: emergency visits decreased by 33.67%, total emergency costs by 45.60%, hospitalizations by 27.15%, and total hospitalization costs by 25.42%. In the second year, reductions were: emergency visits by 28.08%, total emergency costs by 36.10%, hospitalizations by 35.26%, and total hospitalization costs by 18.13% (all P<0.05). Among patients receiving drug therapy, reductions in the first year were: emergency visits by 39.66%, total emergency costs by 47.54%, hospitalizations by 25.19%, and total hospitalization costs by 28.40%. In the second year, reductions were: emergency visits by 46.98%, total emergency costs by 45.99%, hospitalizations by 41.98%, and total hospitalization costs by 24.94% (all P<0.05). No significant differences were observed before and after management for patients without drug treatment. Conclusion:The implementation of the regional hierarchical medical management model based on Medical IoT significantly reduced the frequency of emergency visits and hospitalizations, as well as related costs, for COPD patients.

The clinical features,imaging data and prognosis of 2 patients with spinal cord infarction were summarized.Both patients presented with acute onset paraplegia and urinary retention.Spinal MRI showed high T2 signal and limited diffusion in the spinal cord.Patient 1 had spinal inflammatory changes and disc calcification and herniation at the T6 level.Cervical disc herniation was found in case 2 and the spinal lesions were all adjacent to the spinal infarct plane,but could not directly cause acute or chronic spinal cord compression.The clinical manifestations of two patients were acute stroke events.After the diagnosis of spinal cord infarction was confirmed,anti-platelet aggregation or anticoagulation and rehabilitation therapy were given,and the limb function of the patients gradually recovered to close to normal.The incidence of fibrocartilage embolism(FCE)associated with spinal disc disease is rare,and there is no consensus on treatment.This case provides experience and broadens thinking for the diagnosis,treatment and prognosis of spinal cord infarction.

Metabolic engineering has been developed for nearly 30 years since the early 1990s, and it has given a great impetus to microbial strain breeding and improvement. Aromatic chemicals are a variety of important chemicals that can be produced by microbial fermentation and are widely used in the pharmaceutical, food, feed, and material industry. Microbial cells can be engineered to accumulate a variety of useful aromatic chemicals in a targeted manner through rational engineering of the biosynthetic pathways of shikimate and the derived aromatic amino acids. This review summarizes the metabolic engineering strategies and biosynthetic pathways for the production of aromatic chemicals developed in the past 30 years, with the aim to provide a valuable reference and promote the research in this field.
Biosynthetic Pathways ; Fermentation ; Metabolic Engineering ; Shikimic Acid

Aromatic compounds make up a large part of fragrances and are traditionally produced by chemical synthesis and direct extraction from plants. Chemical synthesis depends on petroleum resources and has disadvantages such as causing environment pollutions and harsh reaction conditions. Due to the low content of aromatic compounds in plants and the low yield of direct extraction, plant extractions require large amounts of plant resources that occupy arable land. In recent years, with the development of metabolic engineering and synthetic biology, microbial synthesis of aromatic compounds from renewable resources has become a promising alternative approach to traditional methods. This review describes the research progress on the synthesis of aromatic fragrances by model microorganisms such as Escherichia coli or yeast, including the synthesis of vanillin through shikimic acid pathway and the synthesis of raspberry ketone through polyketide pathway. Moreover, this review highlights the elucidation of native biosynthesis pathways, the construction of synthetic pathways and metabolic regulation for the production of aromatic fragrances by microbial fermentation.
Biosynthetic Pathways ; Metabolic Engineering ; Odorants ; Shikimic Acid ; Synthetic Biology

Dopamine is the precursor of a variety of natural antioxidant compounds. In the body, dopamine acts as a neurotransmitter that regulates a variety of physiological functions of the central nervous system. Thus, dopamine is used for the clinical treatment of various types of shock. Dopamine could be produced by engineered microbes, but with low efficiency. In this study, DOPA decarboxylase gene from Sus scrofa (Ssddc) was cloned into plasmids with different copy numbers, and transformed into a previously developed L-DOPA producing strain Escherichia coli T004. The resulted strain was capable of producing dopamine from glucose directly. To further improve the production of dopamine, a sequence-based homology alignment mining (SHAM) strategy was applied to screen more efficient DOPA decarboxylases, and five DOPA decarboxylase genes were selected from 100 candidates. In shake-flask fermentation, the DOPA decarboxylase gene from Homo sapiens (Hsddc) showed the highest dopamine production (3.33 g/L), while the DOPA decarboxylase gene from Drosophila Melanogaster (Dmddc) showed the least residual L-DOPA concentration (0.02 g/L). In 5 L fed-batch fermentations, production of dopamine by the two engineered strains reached 13.3 g/L and 16.2 g/L, respectively. The residual concentrations of L-DOPA were 0.45 g/L and 0.23 g/L, respectively. Finally, the Ssddc and Dmddc genes were integrated into the genome of E. coli T004 to obtain genetically stable dopamine-producing strains. In 5 L fed-batch fermentation, 17.7 g/L of dopamine was produced, which records the highest titer reported to date.
Animals ; Dopa Decarboxylase/genetics* ; Dopamine/biosynthesis* ; Drosophila melanogaster/genetics* ; Escherichia coli/metabolism* ; Humans ; Metabolic Engineering

p-coumaric acid is an important natural phenolic compound with a variety of pharmacological activities, and also a precursor for the biosynthesis of many natural compounds. It is widely used in foods, cosmetics and medicines. Compared with the chemical synthesis and plant extraction, microbial production of p-coumaric acid has many advantages, such as energy saving and emission reduction. However, the yield of p-coumaric acid by microbial synthesis is too low to meet the requirements of large-scale industrial production. Here, to further improve p-coumaric acid production, the directed evolution of tyrosine ammonia lyase (TAL) encoded by Rhodotorula glutinis tal gene was conducted, and a high-throughput screening method was established to screen the mutant library for improve the property of TAL. A mutant with a doubled TAL catalytic activity was screened from about 10,000 colonies of the mutant library. There were three mutational amino acid sites in this TAL, namely S9Y, A11N, and E518A. It was further verified by a single point saturation mutation. When S9 was mutated to Y, I or N, or A11 was mutated to N, T or Y, the catalytic activity of TAL increased by more than 1-fold. Through combinatorial mutation of three types of mutations at the S9 and A11, the TAL catalytic activity of S9Y/A11N or S9N/A11Y mutants were significantly higher than that of other mutants. Then, the plasmid containing S9N/A11Y mutant was transformed into CP032, a tyrosine-producing E. coli strain. The engineered strain produced 394.2 mg/L p-coumaric acid, which is 2.2-fold higher than that of the control strain, via shake flask fermentation at 48 h. This work provides a new insight for the biosynthesis study of p-coumaric acid.
Ammonia-Lyases/genetics* ; Escherichia coli/genetics* ; Propionates ; Rhodotorula ; Tyrosine/genetics*

Recently, fast-growing Vibrio natriegens, as the great potential chassis, has shown a wide application in synthetic biology. Genome editing is an indispensable tool for genetic modification in synthetic biology. However, genome editing tools with high efficiency and fidelity are still to be developed for V. natriegens synthetic biology. To deal with this problem, the physiological characteristics of 6 V. natriegens strains were evaluated, and CICC 10908 strain with fast and stable growth was selected as the host strain for genome editing study. Then, the natural transformation system of V. natriegens was established and optimized. The efficiencies of optimized natural transformation that integrates antibiotic resistance marker cat-sacB or Kan(R) onto the chromosome of V. natriegens could reach 4×10⁻⁵ and 4×10⁻⁴, respectively. Based on the optimized natural transformation, a double-selection cassette was used to achieve seamless genome editing with high efficiency and fidelity. The positive rates of four different types of genetic manipulation, including gene deletion, complementation, insertion and substitution, were 93.8%, 100%, 95.7% and 100%, respectively. Finally, transformation and elimination of the recombinant plasmid could be easily achieved in V. natriegens. This work provides a seamless genome editing system with high efficiency and fidelity for V. natriegens synthetic biology.
Gene Editing ; Plasmids/genetics* ; Synthetic Biology ; Vibrio/genetics*

Objective: To investigate factors influencing disease severity in children of Han nationality with atopic dermatitis (AD) in China, and to provide scientific evidences for prevention and treatment of AD in children. Methods: From November 2005 to May 2015, data were collected from AD children aged 0-12 years in Department of Dermatology, The First Affiliated Hospital of Anhui Medical University and AD sample collection collaboration network in China. Statistical analysis was carried out with SPSS16.0 software by using univariate and multivariate ordinal logistic regression analysis to investigate factors influencing the severity of AD. Results: A total of 2 620 children with AD were enrolled into the study, including 230 (8.8%) with mild AD, 1 379 (52.6%) with moderate AD and 1 011 (38.6%) with severe AD. As univariate analysis showed, factors influencing the severity of AD included region, early onset, itching during sweating, xeroderma, ichthyosis, palmar hyperlinearity, lichen pilaris, orbital darkening, scalp dermatitis and infra-auricular fissure (all P<0.01) . There were no significant differences in the severity of AD between different genders, patients with and without personal or family atopic history, or between patients with and without a high serum IgE level (all P > 0.05) . Multivariate ordinal logistic regression analysis showed that southern region (OR = 2.10, 95% CI: 1.76 - 2.51) , early onset (OR = 1.32, 95% CI: 1.01 - 1.71) , itching during sweating (OR = 1.70, 95% CI: 1.42 - 2.02) , xeroderma (OR = 2.57, 95% CI: 2.10 - 3.15) , ichthyosis (OR = 1.49, 95% CI: 1.19 - 1.87) , palmar hyperlinearity (OR = 2.03, 95% CI: 1.61 - 2.57) , lichen pilaris (OR = 1.44, 95% CI: 1.17 - 1.78) , orbital darkening (OR = 1.53, 95% CI: 1.24 - 1.89) , scalp dermatitis (OR = 2.38, 95% CI: 2.01 - 2.82) and infra-auricular fissure (OR = 1.55, 95% CI: 1.31 - 1.85) were positively correlated with the severity of AD (all P<0.05) . Conclusion The severity of AD is associated with patients′ region, early onset, itching during sweating, xeroderma, and other concomitant symptoms.

Objective:To investigate the association between indoleamine 2,3-dioxygenase(IDO)expression in tumor tissue,its periph-eral blood activity, and the efficacy of neoadjuvant chemotherapyin patients with breast cancer. Methods: Immunohistochemistry (IHC)and high-performance liquid chromatography(HPLC)were used to measure IDO protein expression in tumor tissue,and kynuren-ine(Kyn),tryptophan(Trp),and IDO activity(Kyn/Trp)in peripheral blood before neoadjuvant chemotherapy in 53 patients with breast cancer from Tianjin Medical University Cancer Institute and Hospital between September 2015 and December 2016.The correlations between the expression and activity of IDO and the efficacy of chemotherapy were analyzed.Results:In tumor tissue,IDO expression-before neoadjuvant chemotherapy was related to clinical tumor stages(P=0.006),node stages(P=0.020),clinical stages(P=0.045),and estrogen receptor(ER)status(P=0.014).High IDO activity before neoadjuvant chemotherapy in peripheral blood was associated with high IDO expression in tumor tissue(P=0.004),and was also correlated with clinical tumor stages(P=0.019)and node stages(P=0.047). Univariate analysis showed that the clinical efficacy of neoadjuvant chemotherapy was associated with pre-chemotherapeutic clinical tumor stages(P=0.049),ER status(P=0.025),and molecular subtype(P=0.014),while pathologic complete response(pCR)was related to pre-chemotherapeutic clinical tumor stages(P=0.014).Importantly,the clinical efficacy of neoadjuvant chemotherapy and pCR were both related to IDO expression and activity before chemotherapy(all P<0.05).Multivariate analysis showed that pre-chemotherapeu-tic IDO activity in peripheral blood was the only independent factor that affected pCR(P=0.032).Conclusions:Tumor tissue IDO expres-sion and peripheral blood IDO activity before chemotherapy were associated with chemotherapy efficacy,and could provide promising information for the clinical prediction of chemotherapy sensitivity.