L-phosphinothricin (L-PPT) is an efficient broad-spectrum herbicide. To realize the multi-enzyme catalytic preparation of L-PPT, we constructed an engineered strain Escherichia coli YM-1 for efficient expression of D-amino acid transaminase, which could catalyze the generation of the intermediate 2-oxo-4-[(hydroxymethylphosphonyl)] butyric acid (PPO) from D-phosphinothricin (D-PPT). In addition, E. coli pLS was constructed to co-express glutamate dehydrogenase and glucose dehydrogenase, which not only catalyzed the generation of L-PPT from PPO but also regenerated the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH). A fed-batch fermentation process was then established for E. coli YM-1 and pLS, and the apparent activities of D-amino acid transaminase and glutamate dehydrogenase were increased by 22.68% and 100.82%, respectively, compared with those in shake flasks. The process parameters were optimized for the catalytic preparation of L-PPT by whole-cell cascade of E. coli YM-1 and pLS with D, L-PPT as the substrate. After reaction for 8 h, 91.36% conversion of D-PPT was achieved, and the enantiomeric excess of L-PPT reached 90.22%. The findings underpin the industrial production of L-PPT.
Escherichia coli/enzymology* ; Aminobutyrates/metabolism* ; Glutamate Dehydrogenase/biosynthesis* ; Glucose 1-Dehydrogenase/biosynthesis* ; Herbicides/metabolism* ; Multienzyme Complexes/metabolism* ; Transaminases/metabolism* ; Phosphinic Acids/metabolism*

Objective:To evaluate the role of stimulator of interferon genes (STING) in postoperative cognitive dysfunction (POCD) and the relationship with pyroptosis in hippocampal cells in aged mice.Methods:Forty-eight SPF healthy male C57BL/6 mice, aged 18 months, weighing 23-28 g, were assigned to 4 groups ( n=12 each) using a random number table method: control group (C group), POCD group (P group), STING inhibitor C-176 group (PC group), and C-176 solvent group (PV group). The mice underwent Morris water maze training for 4 days prior to model establishment. Mice in P, PC and PV groups underwent tibial fracture and intramedullary pin fixation under sevoflurane anesthesia to establish the POCD model, while mice in C group received no treatment. The STING inhibitor C-176 (750 nmol/200 μl) and an equal volume of C-176 solvent were intraperitoneally injected at 30 min before establishment of the model in PC and PV groups, respectively. The open field test was performed on the 5th day after model preparation, the novel object recognition test was conducted on the 6th day, and the Morris water maze test was performed on the 7th day. Mice were sacrificed under anesthesia to collect the hippocampus for determination of the expression of STING, phosphorylated STING (p-STING), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cleaved caspase-1, and gasdermin-D (GSDMD)-NT by Western blot. Results:There were no statistically significant differences in the parameters of the training phase of the Morris water maze test and the open field test among the four groups ( P>0.05). Compared with C group, the recognition index in the novel object recognition test was significantly decreased, the number of crossing the original platform was reduced and the duration spent in the target quadrant was shortened in the Morris water maze test, and the expression of STING, NLRP3, cleaved caspase-1, and GSDMD-NT in hippocampal neurons was up-regulated in P, PC and PV groups, and the expression of p-STING was significantly up-regulated in P and PV groups ( P<0.05). Compared with P group, the recognition index in the novel object recognition test was significantly increased, the number of crossing the original platform was reduced and the duration spent in the target quadrant was prolonged in the Morris water maze test, and the expression of p-STING, NLRP3, cleaved caspase-1, and GSDMD-NT in hippocampal neurons was down-regulated in PC group ( P<0.05). Compared with PC group, the recognition index in the novel object recognition test was significantly decreased, the number of crossing the original platform was reduced and the duration spent in the target quadrant was shortened in the Morris water maze test, and the expression of p-STING, NLRP3, cleaved caspase-1 and GSDMD-NT was up-regulated in PV group ( P<0.05). Conclusions:STING is involved in the development of POCD in aged mice, and the mechanism may be related to promotion of pyroptosis in hippocampal cells.

Objective:To analyze the changing trends and international differences in the incidence and disability-adjusted life years (DALY) of hypertensive disorders in pregnancy (HDP) in China from 1990 to 2021 based on the Global Burden of Disease (GBD) database.Methods:The data were derived from the GBD database, covering the incidence and DALY data of HDP in countries or regions around the world. Descriptive statistics were used to compare the differences in disease burden between China and different regions of Europe, America and other developed countries, and to analyze the disease burden characteristics of women of childbearing age in different age groups (every 5 years). The Joinpoint regression model was used to identify trend change points. The age-period-cohort model was used to analyze the independent effects of age, period and birth cohort.Results:(1) From 1990 to 2021, the incidence of HDP in China showed an overall downward trend, from 387.18/100 000 in 1990 to 216.35/100 000 in 2021. Compared with the global incidence rate (1990: 1 167.28/100 000; 2021: 923.48/100 000), the incidence rate of HDP in China was relatively low, but it was still higher than that in some developed countries. (2) The analysis of the Joinpoint regression model showed that the incidence rate of HDP in different age groups first decreased, then increased, and finally leveled off. The connection point with the lowest point was in 2005. DALY showed a continuous downward trend in all age groups. Among them, the decline in maternal DALY of pregnant women in all age groups from 15 to 39 years old was more obvious. (3) The age-period-cohort effect model showed that the incidence rate and DALY of HDP in women of childbearing age aged 20 to 24 years reached their peak.Conclusions:The burden of HDP in China continues to decrease, and the disease prevention and control has achieved remarkable results, but the incidence rate is still higher than that in some developed countries. It is suggested that personalized interventions should be developed for different risk groups to further reduce the burden of disease.

Objective:To investigate the mode and timing of delivery in pregnant women with complex fetal congenital heart disease (CHD) detected by prenatal ultrasound.Methods:The clinical data of 123 fetuses with complex CHD detected by prenatal ultrasound in Peking University People′s Hospital from January 2016 to December 2023 were retrospectively analyzed. Pregnant women with indications for prenatal diagnosis underwent G-banding karyotype analysis, single nucleotide polymorphism array (SNP arrry) or whole exome sequencing after informed consent. Integrated managements were provided for pregnant women with complex CHD during pregnancy and perinatal period, and to determine the mode and timing of delivery. Infants with complex CHD received timely treatment or referral after birth.Results:The gestational age at ultrasound diagnosis of the 123 fetuses with complex CHD was (23.7±3.4) weeks. There were 11 cases (8.9%) of total anomalous pulmonary venous connection (TAPVC), 14 cases (11.4%) of anomalous pulmonary valve (PVA), 7 cases (5.7%) of right ventricle double outlet (RVDO), 13 cases (10.6%) of anomalous aortic arch, 69 cases (56.1%) of transposition of the great arteries (TGA), 9 cases (7.3%) of other types. All cases were treated with fetal preservation after prenatal consultation. Among the 72 cases undergoing prenatal diagnosis, 9 cases (12.5%) had chromosomal variations. Fifty-five cases (44.7%, 55/123) underwent trial of labor, of which 46 cases (37.4%, 46/123) had successful vaginal delivery, including 6 cases of forceps delivery, and other 9 cases of failed trial of labor transferred to cesarean section. A total of 77 cases of pregnant women underwent cesarean section. Except for the 21 cases of pregnant women who asked for cesarean section, the cesarean section rate of pregnant women with complex CHD was 45.5% (56/123), which was not significantly different from the average cesarean section rate of the same period in our hospital (40.2%; χ2=7.34, P=0.270). The gestational age at delivery of the 123 fetuses with complex CHD was (37.9±1.4) weeks, the birth weight of the neonates was (3 099±480) g, and the umbilical artery blood pH value was 7.31±0.05. The oxygen saturation of 86 cases before and after alprostadil infusion were (72.8±6.0)% and (80.5±5.0)%, respectively, and the difference was statistically significant ( t=4.38, P<0.001). One hundred and fourteen children underwent surgical treatment, 112 of them (98.2%) had good postoperative reexamination. Only 2 cases (1.8%) died after surgery, and 14.0% (16/114) had the possibility of secondary surgery. Conclusions:Fetal complex CHD is not an indication for cesarean section, and the delivery mode could be selected according to the obstetric situation. If the mother and child are in stable condition, the delivery is planned after 39 weeks of gestation. For children with low oxygen saturation after birth, alprostadil could be pumped to maintain the open ductus arteriosus, and timely referral to the pediatric cardiac surgery for subsequent surgical treatment, which could achieve a good prognosis.

Objective:To compare the efficacy of new nasopharyngeal airway and laryngeal mask airway for airway management in the patients undergoing non-intubated video-assisted thoracoscopic surgery (NIVATS).Methods:In this randomised, controlled, non-inferiority trial, 60 American Society of Anesthesiologists Physical Status classification I or Ⅱ patients of both sexes, aged 18-79 yr, scheduled for elective NIVATS from December 2021 to December 2023 at Jining No.1 People′s Hospital, were divided into 2 groups ( n=30 each) using a computer-generated random code in a 1∶1 ratio: new type nasopharyngeal airway group (group N) and laryngeal mask airway group (group L). After anesthesia induction, a new nasopharyngeal airway was inserted in group N, and a laryngeal mask airway was inserted in group L. Spontaneous ventilation was maintained during the NIVATS. Ultrasound-guided serratus anterior plane block was performed on the affected side before anesthesia induction. Anesthesia was maintained with propofol and remifentanil. The primary outcome measure was the rate of intraoperative airway intervention, the airway interventions included repositioning of the airway tools, manual assisted ventilation, jaw-thrust maneuver, and conversion to endotracheal intubation. The secondary outcome measures included the first-attempt success rate of airway device placement, time for establishing a patent airway, the minimum value of SpO 2, the maximum value of P ETCO 2, and incidence of complications such as postoperative sore throat. Results:The rate of intraoperative airway intervention was 27% in group L and 47% in group N ( χ2=2.58, P=0.108). The difference in the rate of intraoperative airway intervention between the two groups was 0.20 (95% confidence interval 0.15-0.25), with a 95% confidence interval upper limit higher than the non-inferiority boundary (10%), indicating that this non-inferiority hypothesis was not established. In comparison to group L, the rate of intraoperative jaw-thrust maneuver intervention was significantly increased, the time to establish a patent airway was shortened, and the incidence of postoperative sore throat was decreased in group N ( P<0.05). Conclusions:Compared with the laryngeal mask airway, the new nasopharyngeal airway can reduce the development of postoperative throat pain, however, it is less effective in maintaining a patent airway. It requires careful consideration of risks and benefits when used for NIVATS.

Intestinal radiosensitivity makes radiation-induced intestinal injury (RIII) as a common complication among individuals exposed to accidental radiation and patients with abdominal or pelvic malignancies receiving radiotherapy. At present, there are no effective measures for the prevention and treatment of RIII. Developing novel prevention and treatment strategies is of great significance for improving the prognosis and quality of life for both individuals exposed to accidental radiation and cancer patients. Lactobacillus, a Gram-positive bacterium, is widely observed in humans and animals. It exhibits notable probiotic functions, including maintaining gut microbiota homeostasis, preserving intestinal barrier, and modulating immune responses. Substantial studies have demonstrated that Lactobacillus has remarkable protective and therapeutic effects against radiation-induced injury, specifically significantly alleviating RIII. These probiotic functions of Lactobacillus make it have high priority to become the chassis of genetically engineered strains. However, multiple factors influence the construction of a genetically engineered strain, limiting the application of Lactobacillus as a chassis. This review focuses on the probiotic functions of Lactobacillus, highlighting advances in research on Lactobacillus and its engineered probiotics in radiation protection and treatment. Furthermore, it summarizes key factors influencing the construction of genetically engineered strains based on the Lactobacillus chassis. It aims to provide insights for developing genetically engineered strains with radioprotective and therapeutic effects using Lactobacillus as the chassis.

Objective:To explore the value of three-dimensional automatic right ventricular quantitive analysis（3D Auto RVQ）technology in predicting the improvement of left ventricular ejection fraction（LVEF）in patients with heart failure with reduced ejection fraction（HFrEF）.Methods:A retrospective analysis was conducted on 89 HFrEF patients admitted to the Cardiology Department of Central China Fuwai Hospital of Zhengzhou University from April 2022 to June 2024. All patients received medication treatment and were further divided into heart failure with improved ejection fraction（HFimpEF）group and non HFimpEF group based on changes detected by echocardiography in LVEF after treatment. The clinical data，biological indicators，and medication treatment status of patients were collected，routine echocardiographic parameters and right ventricular strain parameters were measured，3D right ventricular ejection fraction（3D-RVEF），3D right ventricular stroke volume index（3D-RVSVI），3D right ventricular end-diastolic volume index（3D-RVEDVI），3D right ventricular end-systolic volume index（3D-RVESVI），3D tricuspid annular plane systolic excursion（3D-TAPSE），and 3D right ventricular fractional area change（3D-RVFAC）were measured using 3D Auto RVQ technology. The differences of the above parameters between the two groups were compared. The ROC curve was used to analyze the predictive efficiency of right ventricular parameters for HFimpEF，and the area under ROC curve（AUC）was calculated and compared. Logistic regression models were used to analyze the predictive value of right ventricular parameters for HFimpEF.Results:Compared with the non HFimpEF group，the HFimpEF group had a younger age，shorter heart failure course，a smaller proportion of males，New York Heart Association（NYHA）functional class ≥Ⅲ，and patients with concomitant coronary heart disease. The baseline LVEF，absolute value of two dimensional right ventricular global longitudinal strain（2D-RVGLS），3D-RVEF，3D-TAPSE，and 3D-RVSVI were higher in the HFimpEF group（all P<0.05）. ROC curve analysis showed that the AUC of 3D-RVEF for predicting HFimpEF was 0.858，and the predictive efficiency was higher than other right ventricular parameters. According to the Yoden index，the optimal cutoff value for predicting HFimpEF based on 3D-RVEF was 36.2%，with a corresponding sensitivity of 84.0% and specificity of 75.0%. After adjusting for clinical and other echocardiographic parameters，the logistic regression model showed that 3D-RVEF was an independent predictor of HFimpEF（ OR=1.435，95% CI=1.145-1.800， P<0.05）. Conclusions:The 3D-RVEF evaluated by 3D Auto RVQ technology has high predictive value for HFimpEF，which can provide a reference for clinical treatment，thereby improving the prognosis of HFrEF patients.

OBJECTIVE: To explore the clinical and genetic characteristics of a child with intellectual development disorder and seizures due to a variant of AP2M1 gene. METHODS: Clinical data of a child with intellectual development disorder and epilepsy who was admitted to the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University in January 2021 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected for whole exome sequencing. Candidate variant was verified by Sanger sequencing and pathogenicity analysis. The three-dimensional structure of the AP2M1 protein was visualized using Chimera v1.10.1 software. Pathogenicity of candidate variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants from the American College of Medical Genetics and Genomics American College of Medical Genetics (ACMG). With "AP2M1 gene" "epilepsy" "intellectual disability" as the keywords, relevant cases were searched from CNKI, Wanfang Data knowledge service platform and PubMed databases with the search time spanning from the establishment of the database to September 2024. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2020-57). RESULTS: The child was a 8-years-and-6-months-old boy, who could raise his head at 3 months and sit alone at 8 months old. He could not walk alone at 1 year old and underwent 2 months' rehabilitation treatment, and could walk alone and call his parents at 1-and-a-half-years-old. At 4-years-and-10-months-old, he started to have frequent seizures, manifesting as low level of consciousness, body shaking, accompanied by blinking, lasting about a few seconds several times a day and could be relieved. With the treatment of sodium valproate combined with lamotrigine, the convulsions were controlled, but his movement and cognition were lagged behind. DNA sequencing revealed that he has harbored a novel variant of the AP2M1 gene (NM_004068.3) c.508C>T (p.Arg170Trp). Sanger sequencing confirmed that both of his parents were of the wild-type. According to the guidelines from the American College for Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PS2+PS4+PM1+PM2+PP2+PP3). The difference between the wild-type and mutant AP2M1 proteins can be clearly viewed through its three-dimensional structure. Two previous reports have included 5 cases due to the same variant. Common manifestations have included seizures (100%, 5/5), motor retardation (100%, 5/5), intellectual impairment (100%, 5/5), autism spectrum disorder (60%, 3/5), ataxia (100%, 5/5), and special facial features (20%, 1/5). CONCLUSION The c.508C>T (p.Arg170Trp) variant of the AP2M1 gene may underlie the intellectual retardation and seizure in this child.
Humans ; Male ; Child ; Intellectual Disability/genetics* ; Seizures/genetics* ; Exome Sequencing ; Mutation

Objective To investigate the application value of late gadolinium enhancement(LEG)at cardiac MRI in predicting ventricular arrhythmia(VA)events in patients after implantation of ICD.Methods A retrospective analysis was performed on 16 patients at high risk of sudden cardi-ac death after ICD implantation and LEG examination in the First and the Sixth Medical Centers of Chinese PLA General Hospital from June 2020 to March 2024.According the occurrence of VA events receiving appropriate ICD therapy during the follow-up period,they were divided into post-operative VA group(7 cases)and non-VA group(9 cases).The correlation of clinical baseline fea-tures and LEG features with VA events was analyzed.Results The ratios of transmural enhance-ment and myocardial medium enhancement were obviously higher in the VA group than the non-VA group(71.4％vs 11.1％,P=0.035;85.7％vs 22.2％,P=0.041).Multivariate logistic regres-sionanalysis showed that transmural enhancement(OR=5.000,95％CI:0.150-166.589,P=0.368)and myocardial medium enhancement(OR=7.000,95％CI:0.217-226.005,P=0.272)were not independent factors influencing VA occurrence.ROC curve analysis indicated that the combined prediction of transmural enhancement and myocardial media enhancement and the pre-diction of transmural enhancement alone had better diagnostic efficacy(P＜0.05).Conclusion LEG has clinical value in predicting postoperative VA events in patients after ICD implantation.