Epidemiology and medical statistics are essential courses for undergraduate students majoring in clinical medicine. By studying the two courses, they can obtain the core skills for their future clinical practice. High-level medical schools both at home and abroad have accumulated successful experiences in curriculum, teaching methods and teaching models of the two disciplines. These colleges have also carried out the exploration of the curriculum reform centering on "organ systems integration". This paper summarizes the current status of epidemiology and medical statistics teaching and curriculum integration in representative medical schools both at home and abroad, and puts forward suggestions for deepening teaching reform and optimizing the curriculum system to provide reference for the integration of epidemiology and medical statistics curriculums for undergraduate students majoring in clinical medicine in China.

Objective:To assess the occurrence, prognosis and possible early risk factors of jaundice in polytrauma patients.Methods:This study was a single-center, prospective study. Polytrauma patients (age>18 years) admitted to Tongji Trauma Center from October 2020 to January 2023 were enrolled. The patients with liver, biliary tract or pancreatic traumatic injury, previously suffered from chronic liver disease were excluded. The clinical characteristics of patients, laboratory test results, imaging examination results, Injury Severity Score (ISS), Glasgow Coma Score and APACHEⅡ score were collected. The incidence of jaundice, the classification of jaundice or the severity of jaundice after multiple injuries, the mortality rate of polytrauma patients with jaundice, and the early independent risk factors of jaundice in polytrauma were analyzed. The differences between the groups were compared by Student’s t test or χ2 test. The independent risk factors of jaundice were analyzed by Logistic regression analyzed. Results:A total of 742 polytrauma patients were included, 34.09% polytrauma patients were accompanied by jaundice, and the ratio of both moderate and severe jaundice were as high as 32.41%. The main type of jaundice was intrahepatic cholestatic jaundice (47.03%). The mortality rate of polytrauma patients accompanied by jaundice was significantly higher than that of polytrauma patients without jaundice (12.25% vs. 3.47%, P<0.001). Logistic regression analysis showed that ISS score ( OR=3.405, 95% CI: 1.962-7.438, P=0.026), plasma lactate ( OR=2.216, 95% CI: 1.203-4.862, P=0.017), interleukin-6 levels ( OR=2.431, 95% CI: 1.424-3.793, P=0.007), the overall duration of parenteral nutrition ( OR=3.011, 95% CI: 1.624-5.041, P=0.022), and the total duration of mechanical ventilation ( OR=3.572, 95% CI: 1.497-4.601, P=0.031) were the early independent risk factors for jaundice in patients after polytrauma. Conclusions:Polytrauma patients are prone to developing jaundice after injury, which is more harmful, especially for intrahepatic cholestatic jaundice after injury. Early identification and early intervention of risk factors associated with jaundice after injury should be strengthened.

As an essential amino acid, l-tryptophan is widely used in food, feed and medicine sectors. Nowadays, microbial l-tryptophan production suffers from low productivity and yield. Here we construct a chassis E. coli TRP3 producing 11.80 g/L l-tryptophan, which was generated by knocking out the l-tryptophan operon repressor protein (trpR) and the l-tryptophan attenuator (trpL), and introducing the feedback-resistant mutant aroG^fbr. On this basis, the l-tryptophan biosynthesis pathway was divided into three modules, including the central metabolic pathway module, the shikimic acid pathway to chorismate module and the chorismate to tryptophan module. Then we used promoter engineering approach to balance the three modules and obtained an engineered E. coli TRP9. After fed-batch cultures in a 5 L fermentor, tryptophan titer reached to 36.08 g/L, with a yield of 18.55%, which reached 81.7% of the maximum theoretical yield. The tryptophan producing strain with high yield laid a good foundation for large-scale production of tryptophan.
Escherichia coli/metabolism* ; Tryptophan ; Metabolic Engineering ; Bioreactors ; Metabolic Networks and Pathways

Adipic acid is a high-value-added dicarboxylic acid which is primarily used in the production of nylon-66 for manufacturing polyurethane foam and polyester resins. At present, the biosynthesis of adipic acid is hampered by its low production efficiency. By introducing the key enzymes of adipic acid reverse degradation pathway into a succinic acid overproducing strain Escherichia coli FMME N-2, an engineered E. coli JL00 capable of producing 0.34 g/L adipic acid was constructed. Subsequently, the expression level of the rate-limiting enzyme was optimized and the adipic acid titer in shake-flask fermentation increased to 0.87 g/L. Moreover, the supply of precursors was balanced by a combinatorial strategy consisting of deletion of sucD, over-expression of acs, and mutation of lpd, and the adipic acid titer of the resulting E. coli JL12 increased to 1.51 g/L. Finally, the fermentation process was optimized in a 5 L fermenter. After 72 h fed-batch fermentation, adipic acid titer reached 22.3 g/L with a yield of 0.25 g/g and a productivity of 0.31 g/(L·h). This work may serve as a technical reference for the biosynthesis of various dicarboxylic acids.
Escherichia coli/metabolism* ; Metabolic Engineering ; Bioreactors ; Fermentation ; Adipates/metabolism*

The use of light energy to drive carbon dioxide (CO₂) reduction for production of chemicals is of great significance for relieving environmental pressure and solving energy crisis. Photocapture, photoelectricity conversion and CO₂ fixation are the key factors affecting the efficiency of photosynthesis, and thus also affect the efficiency of CO₂ utilization. To solve the above problems, this review systematically summarizes the construction, optimization and application of light-driven hybrid system from the perspective of combining biochemistry and metabolic engineering. We introduce the latest research progress of light-driven CO₂ reduction for biosynthesis of chemicals from three aspects: enzyme hybrid system, biological hybrid system and application of these hybrid system. In the aspect of enzyme hybrid system, many strategies were adopted such as improving enzyme catalytic activity and enhancing enzyme stability. In the aspect of biological hybrid system, many methods were used including enhancing biological light harvesting capacity, optimizing reducing power supply and improving energy regeneration. In terms of the applications, hybrid systems have been used in the production of one-carbon compounds, biofuels and biofoods. Finally, the future development direction of artificial photosynthetic system is prospected from the aspects of nanomaterials (including organic and inorganic materials) and biocatalysts (including enzymes and microorganisms).
Carbon Dioxide/metabolism* ; Photosynthesis ; Metabolic Engineering

Succinic acid is an important C4 platform chemical that is widely used in food, chemical, medicine sectors. The bottleneck of fermentative production of succinic acid by engineered Escherichia coli is the imbalance of intracellular cofactors, which often leads to accumulation of by-products, lower yield and low productivity. Stoichiometric analysis indicated that an efficient production of succinic acid by E. coli FMME-N-26 under micro-aeration conditions might be achieved when the TCA cycle provides enough ATP and NADH for the r-TCA pathway. In order to promote succinic acid production, a serial of metabolic engineering strategies include reducing ATP consumption, strengthening ATP synthesis, blocking NADH competitive pathway and constructing NADH complementary pathway were developed. As result, an engineered E. coli FW-17 capable of producing 139.52 g/L succinic acid and 1.40 g/L acetic acid in 5 L fermenter, which were 17.81% higher and 67.59% lower than that of the control strain, was developed. Further scale-up experiments were carried out in a 1 000 L fermenter, and the titer of succinic acid and acetic acid were 140.2 g/L and 1.38 g/L, respectively.
Escherichia coli/genetics* ; NAD ; Succinic Acid ; Acetic Acid ; Adenosine Triphosphate

As a branched chain amino acid, L-valine is widely used in the medicine and feed sectors. In this study, a microbial cell factory for efficient production of L-valine was constructed by combining various metabolic engineering strategies. First, precursor supply for L-valine biosynthesis was enhanced by strengthening the glycolysis pathway and weakening the metabolic pathway of by-products. Subsequently, the key enzyme in the L-valine synthesis pathway, acetylhydroxylate synthase, was engineered by site-directed mutation to relieve the feedback inhibition of the engineered strain. Moreover, promoter engineering was used to optimize the gene expression level of key enzymes in L-valine biosynthetic pathway. Furthermore, cofactor engineering was adopted to change the cofactor preference of acetohydroxyacid isomeroreductase and branched-chain amino acid aminotransferase from NADPH to NADH. The engineered strain C. glutamicum K020 showed a significant increase in L-valine titer, yield and productivity in 5 L fed-batch bioreactor, up to 110 g/L, 0.51 g/g and 2.29 g/(L‧h), respectively.
Valine ; Corynebacterium glutamicum/genetics* ; Metabolic Engineering ; Amino Acids, Branched-Chain ; Bioreactors

Human activities increase the concentration of atmospheric carbon dioxide (CO₂), which leads to global climate warming. Microbial CO₂ fixation is a promising green approach for carbon neutral. In contrast to autotrophic microorganisms, heterotrophic microorganisms are characterized by fast growth and ease of genetic modification, but the efficiency of CO₂ fixation is still limited. In the past decade, synthetic biology-based enhancement of heterotrophic CO₂ fixation has drawn wide attention, including the optimization of energy supply, modification of carboxylation pathway, and heterotrophic microorganisms-based indirect CO₂ fixation. This review focuses on the research progress in CO₂ fixation by heterotrophic microorganisms, which is expected to serve as a reference for peaking CO₂ emission and achieving carbon neutral by microbial CO₂ fixation.
Carbon Cycle ; Carbon Dioxide/metabolism* ; Heterotrophic Processes ; Humans ; Synthetic Biology

Objective : To explore the reform of the operating mechanism of centers for disease control and prevention ( CDCs ) in the new era, and to put forward recommendations. Methods : We collected the financial investment and staffing of CDCs in Zhejiang Province from 2018 to 2020 through China Disease Prevention and Control Information System and Zhejiang Health Statistical Yearbook. We conducted a questionnaire survey among 620 staffs selected by convenience sampling, and a qualitative interview among 40 leaders and experts from CDCs and general hospitals in Zhejiang Province. Results : By the year 2020, there were 105 CDCs in Zhejiang Province, including 1 province-level, 11 prefecture-level, 90 county-level and 3 development zone-level ones. The revenues were mainly from financial subsidy and business incomes, which were over expenditures. There were 7 008 posts in CDCs, with a staffing allocation ratio of 1.29/10 000. Among the reform measures of operation mechanism of CDCs, the flexible communication between clinicians and public health doctors was highly approved (90.03%); among the reform measures of enhancing the integration of prevention and treatment, further clarifying the public health functions of hospitals and ensuring financial compensation was highly approved (74.01%). Conclusion We should further stimulate the endogenous power and vitality of CDCs, strengthen the construction of talent team, promote the active integration of hospitals and CDCs, and improve public health level.

Objective:To prospectively assess clinical characteristics, potential causes and prognosis in patients with persistent inflammation, immunosuppression and catabolism syndrome (PICS) after polytrauma.Methods:Totally 1 083 patients with polytrauma admitted to Department of Traumatic Surgery of Tongji Hospital from Janury 2019 to July 2020 were enrolled. Exclusion criteria included age<18 years old, length of hospital stay<15 days, previous medical history of malignancy, or immunological, consumptive, and metabolic diseases. According to the diagnostic criteria of PICS, all enrolled patients were divided into two groups: PICS group and N-PICS group (without PICS). The patient’s clinical characteristics, ISS score, GCS score, SOFA score, and prognosis were collected. The χ2 test or Student’s t test was uesd to compare the difference between the PICS group and N-PICS group. Results:The incidence of PICS in patients with polytrauma was 11.7% (127/1 083). The majority of PICS patients were middle-aged and elderly men, 68.5% with traumatic brain injury and 59% with thoracic injury. GCS score was significantly lower, while ISS, APACHE II and SOFA scores were significantly higher in the PICS group than in the N-PICS group ( P<0.01, P<0.05). Among PICS patients, 79.5% were treated with mechanical ventilation and 76.3% were associated with pulmonary infection, with a 28-day mortality of 5.5% and a 180-day mortality of 16.5%, which were siginifcantly different from those without PICS. Conclusions:PICS has a high incidence after polytrauma and is commonly seen in middle-aged and elderly male patients with severe polytrauma, especially accompanied by traumatic brain injury or/and thoracic injury. Patients with PICS after polytrauma have poor long-term prognosis, so early identification and intervention should be strengthened in clinical practice.