Amniotic fluid metabolic fingerprinting contributes to shaping the unfavourable intrauterine environment in monochorionic diamniotic twins.

BACKGROUND & AIMS: Amniotic fluid (AF) is the primary intrauterine environment for fetal growth throughout gestation. Selective fetal growth restriction (sFGR) is an adverse complication characterized by unequal growth in twins with nearly identical genetic makeup. However, the influence of AF-mediated intrauterine environment on the development and progression of sFGR remains unexplored. METHODS: High-throughput targeted metabolomics analysis (G350) was performed on AF samples collected from sFGR (n = 18) and MCDA twins with birth weight concordance (MCDA-C, n = 20) cases. Weighted correlation network analysis (WGCNA) was used to identify clinical features that may influence the metabolite composition in AF. Subsequently, partial least-squares discriminant analysis (PLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to compare the different types of sFGR and MCDA-C twins. Receiver operating characteristic (ROC) and multivariate ROC curves were utilized to explore potential AF markers in twins with sFGR. RESULTS: In our study, 182 metabolites were quantified in 76 AF samples. WGCNA indicated that the metabolite composition in late AF may not be influenced by gestational age. PLSDA demonstrated distinct variations between the metabolite profiles of AF in the sFGR and MCDA-C twins, with a significant emphasis on amino acids as the primary differential metabolite. The dissimilarities observed in sFGR twins were predominantly attributed to lipid metabolism-related metabolites. In particular, the KEGG enrichment metabolic pathway analysis revealed significant associations of both types of sFGR twins with central carbon metabolism in cancer. The multivariate ROC curves indicated that the combination of carnosine, sarcosine, l-alanine, beta-alanine, and alpha-n-phenylacetylglutamine significantly improved the AUC to 0.928. Notably, the ROC curves highlighted creatine (AUC:0.934) may be a potential biomarker for severe sFGR. CONCLUSION: The data presented in this study offer a comprehensive metabolic map of the AF in cases of sFGR, shedding light on potential biomarkers associated with fetal growth and development in MCDA twins.

Metabolic dynamics and prediction of sFGR and adverse fetal outcomes: a prospective longitudinal cohort study.

BACKGROUND: Selective fetal growth restriction (sFGR) is an extreme complication that significantly increases the risk of perinatal mortality and long-term adverse neurological outcomes in offspring, affecting approximately 15% of monochorionic diamniotic (MCDA) twin pregnancies. The lack of longitudinal cohort studies hinders the early prediction and intervention of sFGR. METHODS: We constructed a prospective longitudinal cohort study of sFGR, and quantified 25 key metabolites in 337 samples from maternal plasma in the first, second, and third trimester and from cord plasma. In particular, our study examined fetal growth and brain injury data from ultrasonography and used the Ages and Stages Questionnaire-third edition subscale (ASQ-3) to evaluate the long-term neurocognitive behavioral development of infants aged 2-3 years. Furthermore, we correlated metabolite levels with ultrasound data, including physical development and brain injury indicators, and ASQ-3 data using Spearman's-based correlation tests. In addition, special combinations of differential metabolites were used to construct predictive models for the occurrence of sFGR and fetal brain injury. RESULTS: Our findings revealed various dynamic patterns for these metabolites during pregnancy and a maximum of differential metabolites between sFGR and MCDA in the second trimester (n = 8). The combination of L-phenylalanine, L-leucine, and L-isoleucine in the second trimester, which were closely related to fetal growth indicators, was highly predictive of sFGR occurrence (area under the curve [AUC]: 0.878). The combination of L-serine, L-histidine, and L-arginine in the first trimester and creatinine in the second trimester was correlated with long-term neurocognitive behavioral development and showed the capacity to identify fetal brain injury with high accuracy (AUC: 0.94). CONCLUSIONS: The performance of maternal plasma metabolites from the first and second trimester is superior to those from the third trimester and cord plasma in discerning sFGR and fetal brain injury. These metabolites may serve as useful biomarkers for early prediction and promising targets for early intervention in clinical settings.

Synthesis of a Cd-MOF Fluorescence Sensor and Its Detection of Fe3+, Fluazinam, TNP, and Sulfasalazine Enteric-Coated Tablets in Aqueous Solution.

A Cd-based metal-organic framework (Cd-MOF), named after {[Cd(ttc)(H2O)]·H2O}n (ttc = 1-imidazole-1-yl-2,4,6-benzene-tricarboxylic acid), was synthesized using the solvothermal reaction. The single-crystal structure was determined by single X-ray diffraction analysis, and crystalline characteristics and composition were confirmed by powder X-ray diffraction (PXRD) and thermogravimetric analysis (TG), respectively. Structural analysis showed that the Cd2+ ion is in the seven-coordinated mode, in which ttc2- ion adopts the µ4-η1-η1-η2-η2 coordination mode. It is worth noting that the Cd2+ ion is connected to ttc2- to form a 2D network, and the adjacent 2D network is expanded into a 3D supramolecular network structure through weak hydrogen bonds. The fluorescence sensing experiments indicated that Cd-MOF could not only be used as a fluorescence sensor for Fe3+, fluazinam (FLU), and 2,4,6-trinitrophenolol (TNP) but also for sulfasalazine detection in aqueous solution. To verify the sensitivity of the fluorescent probe, we calculated its detection limit: 5.34 × 10-8 M (Fe3+), 7.8 × 10-8 M (FLU), 1.21 × 10-7 M (TNP), and 2.67 × 10-7 M (SECT). In addition, the quenching mechanism was thoroughly studied.

Assisted Reproductive Technology Treatment, the Catalyst to Amplify the Effect of Maternal Infertility on Preterm Birth.

Objective: To identify the influence of different infertility causes and assisted reproductive technology (ART) treatment on perinatal outcomes and clarify the relationship between the maternal pathophysiological changes and artificial interventions. Methods: A total of 1,629 fertile women and 27,112 infertile women with sole infertility causes were prospectively recruited from July 2014 to December 2017, and 9,894 singletons were finally enrolled into the study. Pregnancies with more than one cause of infertility and/or multiple births were excluded. According to the causes of infertility and the exposure of ART treatment, the participants were divided into four groups, namely, fertile naturally conceived (NC) group, infertile NC group, female factor ART group, and male factor ART group. Perinatal outcomes, including gestational age of delivery (GA), birth weight (BW), preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), and large for gestational age (LGA), were compared among groups. Logistic regression was performed for the adjustment of several covariates. Results: The birth outcomes of the infertile NC group and fertile NC group, female factor ART group, and infertile NC group were comparable. Compared to the fertile NC group, the female factor ART group had a shorter GA (39.0 ± 1.6 vs. 39.3 ± 1.5 weeks, BW: P < 0.05). An interaction test showed that ART treatment had an interaction on the effect of female infertility on GA (P = 0.023). The female factor ART group also had a higher risk of PTB (OR 1.56, 95% CI 1.18-2.07) and LGA (OR 1.27, 95% CI 1.10-1.47) compared to the fertile NC group. The risk of PTB was increased for tubal factor ART (OR 1.49, 95% CI 1.12-2.00), ovulatory dysfunction ART (OR 1.87, 95% CI 1.29-2.72), and unexplained infertility ART (OR 1.88, 95% CI 1.11-3.17). The risk of LGA was increased for tubal factor ART (OR 1.28, 95% CI 1.11-1.48) and ovulatory dysfunction ART (OR 1.27, 95% CI 1.03-1.57). Conclusions: Our findings indicated that ART treatment could amplify the adverse effect of female infertility on neonates. Women with tubal factor infertility, ovulatory dysfunction, and unexplained infertility have a higher risk of PTB after ART treatment. Thus, clinicians should be vigilant in such patients and provide corresponding prevention strategies before and during pregnancy.

Periodontal Disease and Adverse Neonatal Outcomes: A Systematic Review and Meta-Analysis.

Objective: The aim of this study was to evaluate the association between maternal periodontal disease (PD) and three main adverse neonatal outcomes, namely, preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA). Methods: The Ovid Medline, Web of Science, Embase, and Cochrane Library were searched up to 6 December 2020 for relevant observational studies on an association between PD and risk of PTB, LBW, and SGA. Eligibility criteria included observational studies which compared the prevalence of PTB and/or LBW and/or SGA between PD women and periodontal health controls. The exclusion criteria included incomplete data, animal research, and mixing up various pregnancy outcomes, such as "preterm low birth weight" and languages other than Chinese and English. Data were extracted and analyzed independently by two authors. The meta-analysis was performed using Stata Statistical Software, Release 12 (StataCorp LP, College Station, TX, USA). Odds ratio (OR), confidence intervals (CIs), and heterogeneity (I 2) were computed. Results: Fourteen case-control studies and 10 prospective cohort studies, involving 15,278 participants, were identified. Based on fixed effect meta-analysis, PTB showed a significant association with PD (OR = 1.57, 95% CI: 1.39-1.77, P < 0.00001) and LBW also showed a significant association with PD (OR = 2.43, 95% CI: 1.75-3.37, P < 0.00001) in a random effect meta-analysis. However, a random effect meta-analysis showed no relationship between PD and SGA (OR = 1.62, 95% CI: 0.86-3.07, P = 0.136). Conclusion: Our findings indicate that pregnant women with PD have a significantly higher risk of PTB and LBW. However, large prospective, blinded cohort studies with standardized diagnostic criteria of PD and adequate control of confounding factors are still required to confirm the relationship between PD and adverse neonatal outcomes.

Thermosensitive Hydrogel for Encapsulation and Controlled Release of Biocontrol Agents to Prevent Peanut Aflatoxin Contamination.

Starch, alginate, and poly(N-isopropylacrylamide) (PNIPAAm) were combined to prepare a semi-interpenetrating network (IPN) hydrogel with temperature sensitivity. Calcium chloride was used as cross-linking agent, the non-toxigenic Aspergillus flavus spores were successfully encapsulated as biocontrol agents by the method of ionic gelation. Characterization of the hydrogel was performed by Fourier-transform infrared spectroscopy (FTIR), scanning electron micrograph (SEM), and thermogravimetry analysis (TGA). Formulation characteristics, such as entrapment efficiency, beads size, swelling behavior, and rheological properties were evaluated. The optical and rheological measurements indicated that the lower critical solution temperature (LCST) of the samples was about 29-30 °C. TGA results demonstrated that the addition of kaolin could improve the thermal stability of the semi-IPN hydrogel. Morphological analysis showed a porous honeycomb structure on the surface of the beads. According to the release properties of the beads, the semi-IPN hydrogel beads containing kaolin not only have the effect of slow release before peanut flowering, but they also can rapidly release biocontrol agents after flowering begins. The early flowering stage of the peanut is the critical moment to apply biocontrol agents. Temperature-sensitive hydrogel beads containing kaolin could be considered as carriers of biocontrol agents for the control of aflatoxin in peanuts.

Efficacy and safety of placing nasoenteral feeding tube with transnasal ultrathin endoscope in critically ill patients.

BACKGROUND: The placement of an enteral feeding tube is the foundation for providing enteral nutrition. But due to the anatomic complexity of the stomach and the duodenum, to a certain degree, there are some technical difficulties in the placement of postpyloric feeding tube, especially in critically ill patients. This study aimed to evaluate the efficacy and safety of placing nasoenteral feeding tube with a transnasal ultrathin endoscope. METHODS: Totally 49 patients, involving 46 (93.9%) being American Society of Anesthesiologists Physical Status (ASA-PS) grade III (n = 3) and grade IV (n = 43), in whom a nasoenteral feeding tube was placed with a transnasal ultrathin endoscope by using over-the-wire technique. The related clinic information during the procedure including success rate, time required, complications and monitoring results of vital signs was analyzed. RESULTS: The tube was placed at or beyond the Treitz's ligament in all of the 49 cases and the total tube-placement success rate was 100% including the one-time tube-placement success rate 95.9%. The tube placement was successful in 46 (93.9%) cases by transnasal method and 3 (6.1%) cases by transoral method. In the 47 cases whose one-time tube-placement success was obtained, the average procedure time was (6.2 +/- 5.6) minutes. For the 3 patients the endoscope inserted transorally due to the failure of transnasal insertion, the total procedure time was (12.3 +/- 2.1) minutes. In the period of nasoenteral tube placement, the average systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and average pulse oxygen saturation (SpO(2)) did not show any significant change. Apart from 3 patients in whom nausea occurred in the procedure and 2 nasal bleeding, no any other acute complications arose. CONCLUSION: The method of placing nasoenteral feeding tube with the transnasal ultrathin endoscope is not only efficient, time-saving, technically simple, and painless to patients, but also safe especially in critically ill patients.

[Application endoscopic mucosal resection to therapy early gastrointestinal cancer and precancerous lesion].

OBJECTIVE: To explore the clinical value of endoscopic mucosal resection (EMR) on early gastrointestinal cancer and precancerous lesion. METHODS: The EMR data of 42 lesions from 28 patients, collected from Apr. 2001 to Dec. 2005, were retrospectively analyzed. All the lesions were confirmed histologically before and after operation. RESULTS: Forty-two lesions were removed by the EMR from 28 patients. Lesion types observed under endoscopy were as follows: type I 9 lesions (type Isp 2 lesions, type Is 7 lesions), type II 33 lesions (type IIa 23 lesions, type IIa + IIc 4 lesions, type IIb 6 lesions). Thirty-eight EMRs were performed by using snare resection techniques and 4 EMRs by using suction cap-assisted techniques. The size of lesions changed from 0.6 cm x 0.6 cm to 3.0 cm x 3.5 cm. Complete resections were achieved in 36 of 40, among them, 2 lesions were divided into 2 pieces and 1 lesion was divided into 3 pieces. Post-EMR histopathologic evaluation revealed the following RESULTS: carcinoma in 4 lesions, high-grade dysplasia (HGD) in 11 lesions, middle-grade dysplasia (MGD) in 17 lesions, adenoma in 6 lesions, non-adenoma in 2 lesions. The pathology match rate between local biopsy and EMR was 60.0%. The detection rates of cancer, HGD and MGD by EMR were higher than that by routine biopsy. No serious complications were seen in this study. CONCLUSION: Endoscopic mucosal resection has significant impact on the endoscopic intervention treatment of early cancer and precancerous lesion in digestive tract.

Effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in premalignant gastric lesions.

AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1,000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy. Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay. RESULTS: The mean of folate concentration in gastric mucosa was 9.03+/-3.37 microg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83+/-3.02 microg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53 expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2 oncogene protein decreased after folic acid therapy. CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.

Construction and high-level expression of a single-chain Fv antibody fragment specific for acidic isoferritin in Escherichia coli.

A functional single-chain Fv antibody fragment (scFv) specific for acidic isoferritin (AIF) was produced at high level in Escherichia coli. The variable regions of heavy chain (V(H)) and light chain (V(L)) from the hybridoma 4c9 were connected with a flexible linker using an assembly polymerase chain reaction. The construct of V(H)-linker-V(L) was inserted into a phagemid pCANTAB 5 E followed by selection with the Recombinant Phage Antibody System (RPAS). Anti-AIF scFv gene from the recombinant phagemid pCAN4c9 was subcloned into pET28a fused to N-terminal His-tag sequence in frame and overexpressed in E. coli BL21(DE3). With an on-column refolding procedure based on Ni-chelating chromatography, the active anti-AIF scFv was recovered efficiently from inclusion bodies with a refolding yield of approximate 75% confirmed by spectrophotometer. The activity of refolded scFv was determined through sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting and enzyme-linked immunosorbent assay. The results showed anti-AIF scFv retains the specific binding activity to AIF with an affinity constant of 7.29 x 10(-8) mol l(-1). The overall yield of anti-AIF scFv with bioactivity in E. coli flask culture was more than 60 mg l(-1).