Background: Isoliquiritigenin, a key pharmacologically active compound derived from the traditional Chinese medicine Glycyrrhizae Radix et Rhizoma, can be further modified into various high-value 5-deoxyflavones, demonstrating significant potential for pharmaceutical development. Currently, the supply of isoliquiritigenin primarily depends on plant extraction. However, heterologous synthesis using microbial cell factories presents a promising alternative, offering a solution to resource limitations caused by the dwindling availability of Glycyrrhiza uralensis. Objective: This study aimed to employ heterologous synthesis in yeast strains for the stable and high-efficiency production of isoliquiritigenin. Methods: First, a stable chassis strain for isoliquiritigenin production was constructed by integrating optimized biosynthetic pathway enzyme genes. A type IV noncatalytic chalcone isomerase-like protein and a synthetic protein scaffold system were employed to enhance the metabolic channeling of key pathway enzymes. Subsequently, yeast metabolism was fine-tuned to balance precursor supply, and cofactor engineering strategies were implemented to increase nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) availability, thereby ensuring the catalytic efficiency of the key enzyme chalcone reductase. Results: The engineered strain Y21-2 achieved a 24.4-fold increase in isoliquiritigenin titer compared to the original strain. Additionally, the proportion of the by-product naringenin chalcone was reduced by 67.8%, marking the first instance in which the ratio of C-5 hydroxylated by-products was minimized to 10.4% during the microbial synthesis of 5-deoxyflavones. Conclusion: This work provides a valuable reference for the efficient and sustainable production of isoliquiritigenin, laying a solid foundation for further pathway optimization and the biotechnological synthesis of other high-value natural 5-deoxyflavones.

Objective To analyze the impact of patients ages on propofol dosage in painless gastroscopy.Methods A retrospective analysis was conducted on the clinical data of 158 painless gastroscopy patients from January 2017 to June 2020.They were divided into the young group(18～44 years old,n = 57),the middle-aged group(45～59 years old,n = 51),and the elderly group(≥60 years old,n = 50)based on their age.The anesthesia status and safety of each group were compared.Results The results showed that the dosage of propofol,average total dosage of propofol,MAP,HR,RR,SpO2 levels in the young group were higher than those in the middle-aged and elderly groups when consciousness disappeared,and the middle-aged group was higher than the elderly group;The onset time,anesthesia recovery time,orientation recovery time,and departure time in the young group of patients were shorter than those in the middle-aged and elderly groups,and the middle-aged group was shorter than the elderly group(P<0.05).The incidence of airway obstruction,hypoxemia,mandible support,mask ventilation,adverse cardiovascular events,sedation related adverse events,and incidence of obstructed endoscopy in the elderly group were higher than those in the young and middle-aged groups.The incidence of smooth endoscopy was lower than that in the young and middle-aged groups(P<0.05).Conclusion Aging may increase the dosage of propofol in patients underwent painless gastroscopy under anesthesia,prolong the onset time,anesthesia recovery time,orientation recovery time,and departure time,increase stress reactions and adverse reactions,and strengthen monitoring for elderly patients in clinical practice.

Objective To observe the clinical effect of multimodal analgesia for painless artificial abortion . Methods 150 cases of ASA Ⅰ-Ⅱ pregnancy received painless artificial abortion operation ,no contraindication for all patients,were randomly divided into the five groups ,30 cases in each group,the blank control group (group S):do not use any analgesia measure ,intravenous injection of 0.9% sodium chloride 2mL preoperation;the fentanyl group ( F group ) :intravenous injection of fentanyl 1μg/kg preoperation ;the parecoxib group ( group P ) :intravenous injection of parecoxib sodium 40mg preoperation.The patients were given painless artificial abortion after injection the above drugs.Nerve block group ( N group):the implementation of painless induced abortion operation after sleep in patients with the cervical nerve block ,injection of 1%lidocaine 2 mL.Multimodal analgesia group (group M):intra-venous injection of parecoxib sodium 40mg,fentanyl 1μg/kg,then the implementation method the same as N group . The operation time,anesthesia onset time,recovery time,time of accurate orientation and additional dosage of propo-fol;incidence rate of artificial abortion syndrome ,the incidence rate of uterine contraction pain ,10min,30min,1h,6h pain scores after operation; adverse reaction;satisfaction score of analgesic effect postoperative 24h were observed. Results The additional dosage of propofol in the group S ,group F,group P,group N and group M were (78.45 ± 20.36)mg,(15.55 ±12.33)mg,(16.75 ±13.13)mg,(14.55 ±10.25)mg,(9.35 ±8.27)mg.The incidence rates of uterine contraction pain in the group S ,group F,group P,group N and group M were 30%,10%,10%,10%,0. Compared with group M ,the additional dosage of propofol and incidence rate of uterine contraction pain in the other four groups were significantly increased (t=3.05,1.82,1.84,1.78,χ2 =72.1,68.2,68.2,68.2,all P<0.05). Pain scores after operation 10min,30min,1h,6h in the group S were (6.6 ±1.5)points,(5.6 ±1.4)points,(4.6 ± 1.1)points,(3.6 ±1.4)points.Those in group F were (5.1 ±1.5)points,(4.3 ±1.1)points,(3.1 ±0.9)points, (2.8 ±0.8).Pain scores after operation 10min,30min,1h,6h in the group P were (4.6 ±1.5) points,(4.2 ± 0.9)points,(2.9 ±0.8) points,(2.7 ±0.6) points.Those in the group N were (4.5 ±1.5) points,(4.1 ± 0.8)points,(2.9 ±0.8)points,(2.6 ±0.5).Pain scores after operation 10min,30min,1h,6h in the group M were (2.2 ±0.8)points,(1.9 ±0.7)points,(1.5 ±0.5)points,(1.2 ±0.3)points.Compared with the group M,pain scores after operation 10min,30min,1h,6h in the other four groups were significantly elevated ( t=2.03,1.96,1.86, 1.84,1.98,1.82,1.80,1.76,2.05,1.99,1.95,1.86,2.06,1.88,1.82,1.76,all P<0.05).Compared with S group,postoperative 24h satisfaction score of analgesia in the group M was improved significantly ( t =1.98,P<0.05).Compared with group M,the incidence rate of nausea in the other four groups was increased significantly (χ2 =72.2,68.9,68.1,68.1,all P<0.05).Conclusion Multimodal analgesia method can greatly reduce artificial abor-tion postoperative pain ,reduce the adverse reactions ,improve patients'satisfaction score ,ensure the safety of operation .