Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

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italic>Platycodon grandiflorum (Jacq.) A. DC is one of the most commonly used bulk medicinal herbs. It has important value in the fields of medicine, food and cosmetics, and its market demand is increasing year by year, and it has a good development prospect. In this study, based on 403 distribution records and 8 environmental variables, we used Maxent model to predict the potential distribution of P. grandiflorum under climate change. The results showed that the model simulation effect was the best when the Maxent parameter was FC (feature combination) = LQPH (L: linear features; Q: quadratic features; P: product features; H: hinge features) and RM (regularization multiplier) = 2.1, AUC (area under curve) = 0.901, and the model prediction showed that P. grandiflorum was widely distributed in 28 provinces of China under the current climate conditions, with a suitable area of 2 337 419.98 km². Under the influence of climate change in the future, the area of suitable habitat of P. grandiflorum showed a decreasing trend, and the distribution center as a whole showed a trend of northward and eastward shift. The distribution area of P. grandiflorum in the three main producing areas is affected by climate change, and the overall trend is that the future suitable distribution area of Chifeng in Inner Mongolia increases, while the future suitable distribution area of Zibo in Shandong and Taihe, Bozhou in Anhui decreases or even disappears under the SSP5-8.5 scenario (shared socioeconomic pathways). It is suggested to maintain and protect the ecological environment and germplasm resources of the reserved area suitable for the growth of P. grandiflorum, and increase the cultivation research in the expansion area of P. grandiflorum, so as to lay a foundation for the subsequent expansion of P. grandiflorum planting and to promote the protection and sustainable development of P. grandiflorum resources.

Objective:To describe the current situation and influencing factors of e-cigarette use among secondary school students in Heilongjiang Province to provide evidence for formulating provincial youth e-cigarette prevention and control strategies.Methods:A multi-stage stratified cluster probability sampling method was adopted in 2021, with 8 340 students in 180 classes from 56 primary and high schools in 10 monitoring districts and counties in Heilongjiang Province. The students in the selected classes filled out a unified questionnaire by themselves. SAS 9.4 software was used for data cleansing, sample weighting, and analysis. Chi-squared tests were used to compare the differences between groups, and a two-level logistic regression model was used to analyze the influencing factors of e-cigarette use among secondary school students.Results:A total of 8 329 survey questionnaires were included in the analysis. The prevalence rates of ever and current e-cigarette use among secondary school students in Heilongjiang Province were 18.27% and 5.46%, respectively. In terms of ever e-cigarette use, the rate of boys (23.94%) was higher than that of girls (12.35%). The rate of vocational high school students (39.18%) was higher than that of general high school students (24.11%) and than that of junior school students (11.27%). In terms of current e-cigarette use, the rate of boys (7.08%) was higher than that of girls (3.76%). The rate of vocational high school students (14.56%) was higher than that of general high school students (7.70%) and than that of junior school students (2.67%). The rates of ever and current e-cigarette use were relatively higher in each subgroup, including "weekly allowance more than 40 Yuan" "one of the student's parents, friends or teachers was smoker" "smoked cigarettes now" and "saw e-cigarette advertisements". A two-level logistic regression model showed that the following factors were the influencing factors of current use of e-cigarettes among secondary school students, including gender, whether they were current cigarette smokers, the smoking status of their close friends, if they saw teachers smoked in the school, noticed e-cigarette advertisements, and e-cigarette addictive cognition.Conclusions:The prevalence rates of ever and current e-cigarette use among secondary school students in Heilongjiang Province were high. E-cigarette advertisements, the smoking status of their close friends, and whether they saw teachers smoking in the school were the main factors affecting e-cigarette use among secondary school students in Heilongjiang Province. It is necessary to focus on constructing smoke-free environments and increase health education related to e-cigarette knowledge on risk in developing a smoke-free campus in the whole province.

OBJECTIVE: To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier. METHODS: Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed. RESULTS: The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months. CONCLUSION Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.
Humans ; Antibodies, Neutralizing ; Prospective Studies ; SARS-CoV-2 ; Breakthrough Infections ; COVID-19 Vaccines ; COVID-19 ; T-Lymphocytes ; China/epidemiology* ; Antibodies, Viral

Objective To analyze the correlation of hepatic steatosis with blood lipids and uric acid metabolism in elderly patients with chronic hepatitis B (CHB). Methods The clinical data of 120 patients with CHB admitted to the hospital from January to December 2021 were retrospectively analyzed. According to the presence or absence of hepatic steatosis, the patients were divided into steatosis group (n=35) and non-steatosis group (n=85). The general clinical data, serological indicators of hepatitis B virus, blood lipid and uric acid levels were compared between the two groups. The correlation of hepatic steatosis grading with blood lipids and uric acid metabolism was analyzed. Results The inflammation and fibrosis degree of liver tissues were significantly different in the two groups (P<0.05). The levels of TG and TC in the steatosis group were higher than those in the non-steatosis group, and the level of HDL-C was lower than that in the non-steatosis group (P<0.05). There was no significant difference between the two groups in LDL-C and uric acid levels (P>0.05). Pearson correlation analysis found that the grade of hepatic steatosis in patients with CHB was negatively correlated with liver tissue inflammation, fibrosis degree and HDL-C level (P<0.05), and positively correlated with TG and TC levels (P<0.05). Conclusion Elderly patients with CHB and hepatic steatosis have abnormal blood lipid metabolism. Hepatic steatosis will exacerbate abnormal blood lipid metabolism but not liver tissue inflammation or fibrosis degree. Clinically, attention should be paid to blood lipid monitoring of elderly patients with CHB.

Congenital extrahepatic portosystemic shunt (CEPS) is also called Abernethy malformation, with the manifestation of congenital abnormal anastomosis between the portal vein and the inferior vena cava. CEPS is extremely rare in clinical practice and has diverse clinical symptoms, which often leads to missed diagnosis and misdiagnosis. This article reviews the pathogenesis, classification, clinical manifestation, diagnosis, and treatment of CEPS, so as to improve the awareness of this disease and provide a reference for further standardization of its diagnosis and treatment process in the future.

Objective: To explore the relationship between low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio with the severity of coronary artery disease and 2-yeat outcome in patients with premature coronary heart disease. Methods: This prospective, multicenter, observational cohort study is originated from the PROMISE study. Eighteen thousand seven hundred and one patients with coronary heart disease (CHD) were screened from January 2015 to May 2019. Three thousand eight hundred and sixty-one patients with premature CHD were enrolled in the current study. According to the median LDL-C/HDL-C ratio (2.4), the patients were divided into two groups: low LDL-C/HDL-C group (LDL-C/HDL-C≤2.4, n=1 867) and high LDL-C/HDL-C group (LDL-C/HDL-C>2.4, n=1 994). Baseline data and 2-year major adverse cardiovascular and cerebrovascular events (MACCE) were collected and analyzed in order to find the differences between premature CHD patients at different LDL-C/HDL-C levels, and explore the correlation between LDL-C/HDL-C ratio with the severity of coronary artery disease and MACCE. Results: The average age of the low LDL-C/HDL-C ratio group was (48.5±6.5) years, 1 154 patients were males (61.8%); the average age of high LDL-C/HDL-C ratio group was (46.5±6.8) years, 1 523 were males (76.4%). The number of target lesions, the number of coronary artery lesions, the preoperative SNYTAX score and the proportion of three-vessel coronary artery disease in the high LDL-C/HDL-C group were significantly higher than those in the low LDL-C/HDL-C group (1.04±0.74 vs. 0.97±0.80, P=0.002; 2.04±0.84 vs. 1.85±0.84, P<0.001; 13.81±8.87 vs. 11.70±8.05, P<0.001; 36.2% vs. 27.4%, respectively, P<0.001). Correlation analysis showed that there was a significant positive correlation between LDL-C/HDL-C ratio and preoperative SYNTAX score, the number of coronary artery lesions, the number of target lesions and whether it was a three-vessel coronary artery disease (all P<0.05). The 2-year follow-up results showed that the incidence of MACCE was significantly higher in the high LDL-C/HDL-C group than that in the low LDL-C/HDL-C group (6.9% vs. 9.1%, P=0.011). There was no significant difference in the incidence of all-cause death, cardiac death, myocardial infarction, stroke, revascularization and bleeding between the two groups. Cox multivariate regression analysis showed that the LDL-C/HDL-C ratio has no correlation with 2-year MACCE, death, myocardial infarction, revascularization, stroke and bleeding events above BARC2 in patients with premature CHD. Conclusion: High LDL-C/HDL-C ratio is positively correlated with the severity of coronary artery disease in patients with premature CHD. The incidence of MACCE of patients with high LDL-C/HDL-C ratio is significantly higher during 2 years follow-up; LDL-C/HDL-C ratio may be an indicator for evaluating the severity of coronary artery disease and long-term prognosis in patients with premature CHD.
Male ; Humans ; Adult ; Middle Aged ; Female ; Coronary Artery Disease/complications* ; Cholesterol, HDL ; Cholesterol, LDL ; Prospective Studies ; Myocardial Infarction/etiology* ; Stroke ; Risk Factors

Objective:To retrieve, evaluate and integrate the best evidence of the operation related to the measurement of intra-abdominal pressure by bladder pressure sensor in adult emergency and critically ill patients.Methods:The "6S" pyramid model was used to retrieve the evidence of internal abdominal pressure measurement at home and abroad, including guidelines, best practices, evidence summary, systematic evaluation, expert consensus and so on. The retrieval time limit was from the establishment of the database to February 12, 2022. Two researchers independently evaluated the quality of the article, extracted data from the included article and graded the evidence according to Joanna Briggs Institute (JBI) evidence pre-grading system (2014 version) .Results:A total of 9 articles were included, including 1 clinical decision, 4 guidelines, 1 expert consensus and 3 quasi-experimental studies. A total of 23 pieces of best evidence were summarized from 10 aspects, including starting time, precautions, patient position, elimination of interference factors, infection control, zero calibration and measurement, data reading, monitoring frequency, equipment management, personnel education and training.Conclusions:This study integrates the best evidence of the operation related to the measurement of intra-abdominal pressure by bladder pressure sensor in adult emergency and critically ill patients, and provides evidence-based basis for standardizing clinical practice and accurately measuring intra-abdominal pressure in adult emergency and critically ill patients.

Objective:To systematically retrieve, evaluate and summarize the research evidence on the measurement method of adult nasogastric tube indwelling length and provide a basis for clinical nursing practice.Methods:To search for Cochrane Library(CD-SR, DARE), Joanna Briggs(JBI), PubMed (MEDLINE), Web of Science electronic database, China Biomedical Literature Database (CBM), Wanfang Database, China Knowledge Network from the establishment of the database to December 2018. Two researchers independently evaluated the quality of the literature and extracted the data.Results:A total of 9 articles were included in the study. The recommended anatomical landmarks for measuring the length of the inserted gastric tube included XNE, NEX, XJN, Hanson method, GWNUF model, earlobe to xiphoid to navel-nose tip to earlobe NEX 10 cm. The tip of the nasogastric tube and all its lateral hole locations obtained by the Hanson method, the GWNUF model, and the XEN 10 cm method were more likely to be located in the stomach.Conclusion:Although NEX is an external measurement method that is widely used in clinical practice, it has proven to be insufficiently accurate and has considerable risks. Therefore, the method of measuring the length of the nasogastric tube insertion should be carefully selected for teaching or use in practice.