Objective:To investigate the echocardiographic features, consistency of diagnosis between fetal and postnatal periods and postnatal clinical outcomes of fetal pulmonary valve stenosis (PS) with different degrees.Methods:This study was a retrospective cohort study comprising 108 cases of fetal PS diagnosed during the fetal period and followed up postnatally at Xinhua Hospital, Shanghai Jiaotong University School of Medicine from November 2012 to February 2023. Echocardiographic characteristics, including morphological and hemodynamic features were collected for all fetuses who were then were followed up to at least 6 months after birth. One-way analysis of variance and Kruskal-Wallis test were used to compare the differences in the echocardiographic features among fetuses with different degrees of PS. Subsequently, McNemar test was used to assess the consistency of diagnosis between the fetal and postnatal periods. Furthermore, Logistic regression analysis was applied to explore the risk factors for neonatal intervention in fetuses with moderate PS and the receiver operating characteristic (ROC) curve was utilized to ascertain the optimal cut-off value for continuous variables.Results:The age of the mothers of the 108 fetuses at the initial assessment was (30.8±4.0) years, and the gestational age was 26.5 (24.6, 30.0) weeks. The fetuses were categorized into mild (17 cases), moderate (49 cases), and severe groups (42 cases) based on the initial echocardiographic features. Mild PS was characterized by valve thickening and hyperechogenicity combined with systolic flow acceleration or dilation of main pulmonary artery. Moderate PS exhibited both restricted valve motion and a colorful blood flow pattern at the valve orifice. The peak flow velocities of fetuses with moderate and critical PS were notably higher than those in the mild group ((2.66±0.86) and (2.77±1.30) vs. (1.43±0.59)m/s, F=14.52, P<0.001). In critical PS, all cases showed retrograde ductal flow, with a significantly higher proportion of a small right ventricle compared to the mild and moderate PS (42.9% (18/42) vs. 0 and 2.0% (1/49), χ2=31.73, P<0.001). The proportion of severe tricuspid regurgitation was also higher (35.7% (15/42) vs. 0 and 10.2% (5/49), χ2=36.94, P<0.001). Compared to mild and severe PS, the consistency of diagnosis between fetal and postnatal periods in moderate PS was lower (40.8% (20/49) vs.13/17 and 80.3% (35/42), χ 2=12.45, P=0.006). The systolic flow velocity was identified as an independent risk factor for neonatal intervention in fetuses with moderate PS ( OR=7.21, 95% CI2.11-24.62). A flow velocity of ≥2.18 m/s in second trimester and ≥3.15 m/s in third trimester indicated the necessity of neonatal intervention for fetal moderate PS. Among the 108 fetuses, 68 underwent surgical intervention and all survived. Additionally, 39 fetuses were regularly followed up. A sole non-surgical fatality occurred, leading to a 6-month survival rate of 99.1% (107/108). Conclusions:Various degrees of fetal PS demonstrate distinctive morphological and hemodynamic alterations in echocardiography. The disparity in severity between the postnatal and fetal stages requires ongoing monitoring for fetal PS. The prognosis for fetal PS is generally favorable.

Tyrosol is a natural polyphenolic product that is widely used in chemical, pharmaceutical and food industries. Currently, the de novo synthesis of tyrosol by Escherichia coli suffers from issues such as low cell density and poor yield. Therefore, the phenylpyruvate decarboxylase mutant ARO10^F138L/D218G obtained in our previous study was fused with an alcohol dehydrogenase from different microorganisms for fusion expression, and the optimal ARO^{10F138L/D218G}-L-YahK produced 1.09 g/L tyrosol in shake flasks. In order to further improve tyrosol production, feaB, a key gene in the competing pathway of 4-hydroxyphenylacetic acid, was knocked out, and the resulted strain produced 1.26 g/L tyrosol with an increase of 21.15% compared to that of the control. To overcome the low cell density in tyrosol fermentation, the quorum-sensing circuit was used to dynamically regulate the tyrosol synthesis pathway, so as to alleviate the toxic effect of tyrosol on chassis cells and relieve the growth inhibition. Using this strategy, the yield of tyrosol was increased to 1.74 g/L, a 33.82% increase. In a 2 L fermenter, the production of tyrosol in the engineered strain TRFQ5 dynamically regulated by quorum-sensing reached 4.22 g/L with an OD₆₀₀ of 42.88. Compared with those in the engineered strain TRF5 statically regulated by induced expression, the yield was increased by 38.58% and the OD₆₀₀ was enhanced by 43.62%. The combination of blocking the competing pathway using gene knockout technology, and reducing the inhibitory effect of tyrosol toxicity on chassis cells through quorum-sensing dynamic regulation increased the production of tyrosol. This study may facilitate the biosynthesis of other chemicals with high toxicity.
Escherichia coli/genetics* ; Biological Products ; Bioreactors ; Fermentation

In order to improve the teaching quality of engineering courses, we introduced a multi-dimensional teaching method into the teaching reform of biology majors in colleges based on the portfolio assessment in the curriculum of Cell Engineering. We reformed the knowledge system, teaching form and implementation scheme of this course. By combining the reform of online teaching, interactive teaching, case teaching and other teaching modes, the students mastered the relevant professional knowledge and the scientific and technological frontier of Cell Engineering. Moreover, their learning interest and enthusiasm, ability of analyzing and solving professional problems related to Cell Engineering also improved. The implementation of teaching reform of this course provides a reference for other similar professional courses in colleges.
Humans ; Curriculum ; Students ; Learning ; Cell Engineering

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

OBJECTIVE To understand the safety of Ilaprazole sodium for injection in clinical practice. METHODS From Jan. 1st 2019 to Feb. 29th 2020， the data of 3 926 valid hospitalized patients receiving Ilaprazole sodium for injection were collected prospectively from 5 third-level hospitals through CHPS， and the post-marketing safety analysis was performed by using retrospective multicenter single cohort study. At the same time， a nested case-control study （the ratio of trial group and control group was 1∶4） was used to confirm the baseline stability of this study cohort and the correlation between adverse reactions and Ilaprazole sodium for injection. RESULTS Among 3 926 patients， 3 patients experienced 5 adverse drug events after using Ilaprazole sodium for injection， with the incidence of 0.076%. There was no serious adverse event， and the occurrence time was 2 days after medication； adverse drug events mainly include elevated liver function indicators （alanine transaminase， aspartate transaminase， total bilirubin）， which were mild and untreated， and all adverse drug events were improved. The results of the nested case-control study showed that the trial group and the control group belonged to the same background baseline， and the occurrence of adverse drug events was more closely related to Ilaprazole sodium for injection. CONCLUSIONS The overall safety of Ilaprazole sodium for injection is relatively high， and the occurrence of adverse events is more related to it.

Deinagkistrodon acutus(also known as the five-paced viper and the traditional Chinese medicine ingredient is called Agkistrodon) venom is a viscous liquid from the venom glands of the Deinagkistrodon acutus. It contains a variety of protein and peptide components such as phospholipase A2, serine protease, metalloproteinase, C-type lectin, L-amino acid oxidase, and has a variety of biological activities, playing an important role in anti-tumour, anti-thrombotic, anti-inflammatory and anti-bacterial activities. In recent years, snake venom research has become increasingly widespread, but there is still a lack of comprehensive and systematic studies on snake venom from Deinagkistrodon acutus. In this paper, the source, identification, active ingredients, toxicity studies and quality researches of Deinagkistrodon acutus venom are summarized and analysed by searching the related research progress, in order to provide reference for further development and utilization of Deinagkistrodon acutus venom.

Genome sequences of 4 644 representative strains from human gut microbiota were analyzed to mine gene clusters for biosynthesis of novel secondary metabolites, as well as genes encoding antibiotic resistance and virulence factors. AntiSMASH analysis showed that more than 60% of the representative strains encoded at least one secondary metabolite gene cluster, and 8 potential novel secondary metabolite gene clusters were identified from 8 unculturable bacteria. The secondary metabolite gene clusters in human intestine are mainly composed of nonribosomal peptide synthetase (NRPS), bacteriocin, arylpolyene, terpene, betalactone and NRPS like gene clusters distributed in Clostridia, Bacilli, Gammaproteobacteria, Bacteroidia, Actinobacteria and Negativicutes. PathoFact analysis showed that genes encoding antibiotic resistance and virulence factors are widely distributed in representative strains, but the frequency encoded by potential pathogens is significantly higher than that of non-potential pathogens. The frequency of genes encoding secretory toxins such as outer membrane protein, PapC N-terminal domain, PapC C-terminal domain, peptidase M16 inactive domain, and non-secretory toxins such as nitroreductase family, AcrB/AcrD/AcrF family, PLD-like domain, Cupin domain, putative hemolysin, S24-like peptidase, phosphotransferase enzyme family, endonuclease/ exonuclease/ phosphatase family, glyoxalase/ bleomycin resistance was high in potential pathogens. This study may facilitate mining new microbial natural products from the intestinal microbiome, understanding the colonization and infection mechanism of intestinal microorganisms, and providing targeted prevention and treatment of intestinal microbial related diseases.
Humans ; Virulence ; Multigene Family ; Bacteria ; Drug Resistance, Microbial ; Virulence Factors ; Peptide Hydrolases

We introduce the portfolio assessment into the classroom teaching reform in the curriculum of Cell Engineering, a specialty course in bioengineering & biotechnology. We established a complete classroom evaluation system that was divided the classroom assessment system of portfolio into four stages including the preparation stage, training stage, implementation stage and exhibition stage. We also discuss the feasibility and necessity of implementing the portfolio evaluation method in the course of cell engineering, the construction of evaluation system, and the key points and matters needing attention in the implementation process. The classroom reform is very productive, not only the classroom atmosphere has been activated, students' learning initiative and autonomy has been enhanced, but also the students' ability to analyze and solve professional problems related to cell engineering technology has been improved. The implementation of classroom teaching reform of this course can provide reference for other similar professional courses in colleges and universities.
Cell Engineering ; Curriculum ; Humans ; Learning ; Students ; Universities

Immunoglobulin Y (IgY) is an effective orally administered antibody used to protect against various intestinal pathogens, but which cannot tolerate the acidic gastric environment. In this study, IgY was microencapsulated by alginate (ALG) and coated with chitooligosaccharide (COS). A response surface methodology was used to optimize the formulation, and a simulated gastrointestinal (GI) digestion (SGID) system to evaluate the controlled release of microencapsulated IgY. The microcapsule formulation was optimized as an ALG concentration of 1.56% (15.6 g/L), COS level of 0.61% (6.1 g/L), and IgY/ALG ratio of 62.44% (mass ratio). The microcapsules prepared following this formulation had an encapsulation efficiency of 65.19%, a loading capacity of 33.75%, and an average particle size of 588.75 μm. Under this optimum formulation, the coating of COS provided a less porous and more continuous microstructure by filling the cracks on the surface, and thus the GI release rate of encapsulated IgY was significantly reduced. The release of encapsulated IgY during simulated gastric and intestinal digestion well fitted the zero-order and first-order kinetics functions, respectively. The microcapsule also allowed the IgY to retain 84.37% immune-activity after 4 h simulated GI digestion, significantly higher than that for unprotected IgY (5.33%). This approach could provide an efficient way to preserve IgY and improve its performance in the GI tract.
Alginic Acid/chemistry* ; Chitin/chemistry* ; Chitosan ; Delayed-Action Preparations ; Digestion ; Drug Compounding ; Drug Liberation ; Gastrointestinal Tract/metabolism* ; Immunoglobulins/metabolism* ; Oligosaccharides

Objective: To understand the incidence and mortality of colorectal cancer in tumor registration areas of Zhejiang Province,and to provide reference for prevention and control strategies for colorectal cancer. Methods: The colorectal cancer data was retrieved from fourteen tumor registries in Zhejiang Province were collected,the incidence rate and mortality rate were calculated and standardized according to the Chinese standard population in 2010 and Segi's world population in 2000. The incidence and mortality of colorectal cancer in different sex,age group and region were analyzed. Results: The crude incidence rate of colorectal cancer from 2010 to 2014 was 35.82/100 000（20 983 cases）. The standardized incidence rate by Chinese and world standard population were 20.80/100 000 and 23.01/100 000. The crude mortality rate of colorectal cancer was 15.25/100 000 （8 934 cases）. The standardized mortality rate by Chinese and world standard population were 8.01/100 000 and 9.39/100 000. The ratio of mortality to incidence was 0.43:1. From 2010 to 2014,the incidence and mortality rates of colorectal cancer were stable（P>0.05）. The incidence rates of colorectal cancer in urban and rural residents were 37.69/100 000 and 31.14/100 000,and the mortality rates were 15.73/100 000 and 14.05/100 000. The incidence rates of colorectal cancer in males and females were 41.53/100 000 and 30.11/100 000,and the mortality rates were 17.74/100 000 and 12.76/100 000. The incidence and mortality rates of colorectal cancer both increased with age. The incidence rate increased significantly in people after 40 years old,and peaked with 187.35/100 000 in people aged 80-84 years. The morbidity rate peaked with 171.27/100 000 in people aged 85 years or over. Conclusion The incidence and mortality of colorectal cancer in Zhejiang Province were stable,but the incidence was higher than the national average level. The incidence of colorectal cancer in people aged over 40 years increased significantly.