FLRT3 and TGF-ß/SMAD4 signalling: Impacts on apoptosis, autophagy and ion channels in supraventricular tachycardia.

To explore the underlying molecular mechanisms of supraventricular tachycardia (SVT), this study aimed to analyse the complex relationship between FLRT3 and TGF-ß/SMAD4 signalling pathway, which affects Na+ and K+ channels in cardiomyocytes. Bioinformatics analysis was performed on 85 SVT samples and 15 healthy controls to screen overlapping genes from the key module and differentially expressed genes (DEGs). Expression profiling of overlapping genes, coupled with Receiver Operating Characteristic (ROC) curve analyses, identified FLRT3 as a hub gene. In vitro studies utilizing Ang II-stimulated H9C2 cardiomyocytes were undertaken to elucidate the consequences of FLRT3 silencing on cardiomyocyte apoptosis and autophagic processes. Utilizing a combination of techniques such as quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blotting (WB), flow cytometry, dual-luciferase reporter assays and chromatin immunoprecipitation polymerase chain reaction (ChIP-PCR) assays were conducted to decipher the intricate interactions between FLRT3, the TGF-ß/SMAD4 signalling cascade and ion channel gene expression. Six genes (AADAC, DSC3, FLRT3, SYT4, PRR9 and SERTM1) demonstrated reduced expression in SVT samples, each possessing significant clinical diagnostic potential. In H9C2 cardiomyocytes, FLRT3 silencing mitigated Ang II-induced apoptosis and modulated autophagy. With increasing TGF-ß concentration, there was a dose-responsive decline in FLRT3 and SCN5A expression, while both KCNIP2 and KCND2 expressions were augmented. Moreover, a direct interaction between FLRT3 and SMAD4 was observed, and inhibition of SMAD4 expression resulted in increased FLRT3 expression. Our results demonstrated that the TGF-ß/SMAD4 signalling pathway plays a critical role by regulating FLRT3 expression, with potential implications for ion channel function in SVT.

4D-Printed Elution-Peak-Guided Dual-Responsive Monolithic Packing for the Solid-Phase Extraction of Metal Ions.

Four-dimensional printing (4DP) technologies are revolutionizing the fabrication of stimuli-responsive devices. To advance the analytical performance of conventional solid-phase extraction (SPE) devices using 4DP technology, in this study, we employed N-isopropylacrylamide (NIPAM)-incorporated photocurable resins and digital light processing three-dimensional printing to fabricate an SPE column with a [H+]/temperature dual-responsive monolithic packing stacked as interlacing cuboids to extract Mn, Co, Ni, Cu, Zn, Cd, and Pb ions. When these metal ions were eluted using 0.5% HNO3 solution as the eluent at a temperature below the lower critical solution temperature of polyNIPAM, the monolithic packing swelled owing to its hydrophilic/hydrophobic transition and electrostatic repulsion among the protonated units of polyNIPAM. These effects resulted in smaller interstitial volumes among these interlacing cuboids and improvements in the elution peak profiles of the metal ions, which, in turn, demonstrated the reduced method detection limits (MDLs; range, 0.2-7.2 ng L-1) during analysis using inductively coupled plasma mass spectrometry. We studied the effects of optimizing the elution peak profiles of the metal ions on the analytical performance of this method and validated its reliability and applicability by analyzing the metal ions in reference materials (CASS-4, SLRS-5, 1643f, and Seronorm Trace Elements Urine L-2) and performing spike analyses of seawater, groundwater, river water, and human urine samples. Our results suggest that this 4D-printed elution-peak-guided dual-responsive monolithic packing enables lower MDLs when packed in an SPE column to facilitate the analyses of the metal ions in complex real samples.

Sequestration of Labile Organic Matter by Secondary Fe Minerals from Chemodenitrification: Insight into Mineral Protection Mechanisms.

Labile organic matter (OM) immobilized by secondary iron (Fe) minerals from chemodenitrification may be an effective way to immobilize organic carbon (OC). However, the underlying mechanisms of coupled chemodenitrification and OC sequestration are poorly understood. Here, OM immobilization by secondary Fe minerals from chemodenitrification was investigated at different C/Fe ratios. Kinetics of Fe(II) oxidation and nitrite reduction rates decreased with increasing C/Fe ratios. Despite efficient sequestration, the immobilization efficiency of OM by secondary minerals varied with the C/Fe ratios. Higher C/Fe ratios were conducive to the formation of ferrihydrite and lepidocrocite, with defects and nanopores. Three contributions, including inner-core Fe-O and edge- and corner-shared Fe-Fe interactions, constituted the local coordination environment of mineral-organic composites. Microscopic analysis at the molecular scale uncovered that labile OM was more likely to combine with secondary minerals with poor crystallinity to enhance its stability, and OM distributed within nanopores and defects had a higher oxidation state. After chemodenitrification, high molecular weight substances and substances high in unsaturation or O/C ratios including phenols, polycyclic aromatics, and carboxylic compounds exhibited a stronger affinity to Fe minerals in the treatments with lower C/Fe ratios. Collectively, labile OM immobilization can occur during chemodenitrification. The findings on OM sequestration coupled with chemodenitrification have significant implications for understanding the long-term cycling of Fe, C, and N, providing a potential strategy for OM immobilization in anoxic soils and sediments.

Urine cadmium and urolithiasis: A systematic review and meta-analysis.

Exposure to cadmium may increase risk of urolithiasis, but the results remain inconclusive. This systematic review and meta-analysis aimed to access the association between cadmium exposure and urolithiasis. We searched Medline/PubMed, Embase, Web of Science Core Collection, and Cochrane Central for studies. The primary outcome was the incidence of urolithiasis compared to reference groups. We used relative risk as the summary effect measure. This meta-analysis included eight observational studies and divided into 39 study populations. Among 63,051 subjects, 5018 (7.96%) individuals had urolithiasis. The results indicated that people with an increment of 0.1 µg/g creatinine in urinary cadmium had a 2% increased risk of urolithiasis (pooled relative risk [RR], 1.02; 95% confidence interval [CI], 1.01-1.03) and there is no difference in the risk of urolithiasis in high and low cadmium exposure levels. Meanwhile, people with an increment of 0.1 µg/L in urinary cadmium had a 4% increased risk of urolithiasis (pooled RR, 1.04; 95% CI, 1.02-1.07). Our findings also showed similar associations in both sex, different region (Sweden, China, and Thailand), general and occupational population. The results indicate that cadmium exposure was significantly associated with an elevated risk of urolithiasis. Therefore, it is imperative to take steps to minimize cadmium exposure.

3D-printed thermally expanded monolithic foam for solid-phase extraction of multiple trace metals.

Digital light processing (DLP) 3DP, commercial acrylate-based photocurable resins, and thermally expandable microspheres-incorporated flexible photocurable resins were employed to fabricate an SPE column with a thermally expanded monolithic foam for extracting Mn, Co, Ni, Cu, Zn, Cd, and Pb ions prior to the determination using inductively coupled plasma mass spectrometry. After optimization of the thermally activated foaming, the design and fabrication of the SPE column, and the automatic analytical system, the DLP 3D-printed SPE column with the thermally expanded monolithic foam extracted the metal ions with up to 14.8-fold enhancement (relative to that without incorporating the microspheres), with absolute extraction efficiencies all higher than 95.6%, and method detection limits in the range from 0.5 to 5.2 ng L-1. We validated the reliability and applicability of this method by determination of the metal ions in several reference materials (CASS-4, SLRS-5, 1643f, and Seronorm Trace Elements Urine L-2) and spiked seawater, river water, ground water, and human urine samples. The results illustrated that to incorporate the thermally expandable microspheres into the photocurable resins with a post-printing heating treatment enabled the DLP 3D-printed thermally expanded monolithic foam to substantially improve the extraction of the metal ions, thereby extending the applicability of SPE devices fabricated by vat photopolymerization 3DP techniques.

Rapid Determination of 12 Classes of Per- and Polyfluoroalkyl Substances in Water Samples from Environmental Forensic Cases.

The widespread use of per- and polyfluoroalkyl substances (PFASs) with different physico-chemical properties poses a great threat to the environment and human health. Simultaneous detection of different classes of PFASs is a difficult task, especially for rapid analysis of polluted water samples in environmental forensic cases. In this study, a simple sample preparation ultrahigh-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was established for the detection of PFASs in a wide range of water matrices. By optimizing the conditions of pretreatment and the parameters of the instrument, the developed method provided good linearity of calibration standards (R2 > 0.99), and demonstrated excellent MLOQ (0.008-1.2 µg/L), with spiked recoveries ranging from 57.7% to 151% for 47 targets in surface water samples, and from 45.7 to 165% for 46 targets in ground and waste water samples, respectively. This method required an injection volume of 3 µL and an analysis time of only 18 min per sample. The validation method was successfully applied to the analysis of 20 environmental water samples, in which 15 target substances with different concentrations were detected, with total concentrations of 0.082 to 262.455 µg/L. The method is simple and exclusive, and can rapidly confirm the occurrence of PFASs in different water samples, providing a convenient and fast high-throughput analysis, which is especially suitable for the application in the environmental forensic investigation of PFASs pollution.

[Application of optical genome mapping technology for the detection of chromosomal structural variations].

OBJECTIVE: To assess the value of optical genome mapping (OGM) for the detection of chromosomal structural abnormalities including ring chromosomes, balanced translocations, and insertional translocations. METHODS: Clinical data of four patients who underwent pre-implantation genetic testing concurrently with OGM and chromosomal microarray analysis at the Center of Reproductive Medicine of the Sixth Affiliated Hospital of Sun Yat-sen University from January to October 2022 due to chromosomal structural abnormalities were selected as the study subjects. Some of the results were verified by multi-color fluorescence in situ hybridization. RESULTS: The OGM has successfully detected a balanced translocation and fine mapped the breakpoints in a patient. Among two patients with insertional translocations, OGM has provided more refined breakpoint locations than karyotyping analysis in a patient who had chromosome 3 inserted into chromosome 6 and determined the direction of the inserted fragment. However, OGM has failed to detect the chromosomal abnormality in a patient with chromosome 8 inserted into the Y chromosome. It has also failed to detect circular signals in a patient with ring chromosome mosaicism. CONCLUSION: OGM has successfully detected chromosomal structural variations in the four patients and provided assistance for their diagnosis.

Effects of zero-valent iron added in the flooding or drainage process on cadmium immobilization in an acid paddy soil.

Zero-valent iron (ZVI) is a promising material for the remediation of Cd-contaminated paddy soils. However, the effects of ZVI added during flooding or drainage processes on cadmium (Cd) retention remain unclear. Herein, Cd-contaminated paddy soil was incubated for 40 days of flooding and then for 15 days of drainage, and the underlying mechanisms of Cd immobilization coupled with Fe/S/N redox processes were investigated. The addition of ZVI to the flooding process was more conducive to Cd immobilization. Less potential available Cd was detected by adding ZVI before flooding, which may be due to the increase in paddy soil pH and newly formed secondary Fe minerals. Moreover, the reductive dissolution of Fe minerals promoted the release of soil colloids, thereby increasing significantly the surface sites and causing Cd immobilization. Additionally, the addition of ZVI before flooding played a vital role in Cd retention after soil drainage. In contrast, the addition of ZVI in the drainage phase was not conducive to Cd retention, which might be due to the rapid decrease in soil pH that inhibited Cd adsorption and further immobilization on soil surfaces. The findings of this study demonstrated that Cd availability in paddy soil was largely reduced by adding ZVI during the flooding period and provide a novel insight into the mechanisms of ZVI remediation in Cd-contaminated paddy soils.

The double-edged sword effect of HDAC6 in Aß toxicities.

Alzheimer's disease (AD) is marked by cognitive impairment, massive cell death, and reduced life expectancy. Pathologically, accumulated beta-amyloid (Aß) aggregates and hyperphosphorylated tau protein is the hallmark of the disease. Although changes in cellular function and protein accumulates have been demonstrated in many different AD animal models, the molecular mechanism involved in different cellular functions and the correlation and causative relation between different protein accumulations remain elusive. Our in vivo genetic studies revealed that the molecular mechanisms involved in memory loss and lifespan shortening are different and that tau plays an essential role in mediating Aß-induced early death. We found that when the first deacetylase (DAC) domain of histone deacetylase 6 (HDAC6) activity was increased, it regulated cortactin deacetylation to reverse Aß-induced learning and memory deficit, but with no effect on the lifespan of the Aß flies. On the other hand, an increased amount of the second DAC domain of HDAC6 promoted tau phosphorylation to facilitate Aß-induced lifespan shortening without affecting learning performance in the Aß flies. Our data also confirmed decreased acetylation in two major HDAC6 downstream proteins, suggesting increased HDAC6 activity in Aß flies. Our data established the double-edged sword effect of HDAC6 activity in Aß-induced pathologies. Not only did we segregate memory loss and lifespan shortening in Aß flies, but we also provided evidence to link the Aß with tau signaling.

Fe(II) Oxidation Shaped Functional Genes and Bacteria Involved in Denitrification and Dissimilatory Nitrate Reduction to Ammonium from Different Paddy Soils.

Microbial nitrate reduction can drive Fe(II) oxidation in anoxic environments, affecting the nitrous oxide emission and ammonium availability. The nitrate-reducing Fe(II) oxidation usually causes severe cell encrustation via chemodenitrification and potentially inhibits bacterial activity due to the blocking effect of secondary minerals. However, it remains unclear how Fe(II) oxidation and subsequent cell encrustation affect the functional genes and bacteria for denitrification and dissimilatory nitrate reduction to ammonium (DNRA). Here, bacteria were enriched from different paddy soils with and without Fe(II) under nitrate-reducing conditions. Fe(II) addition decelerated nitrate reduction and increased NO2- accumulation, due to the rapid Fe(II) oxidation and cell encrustation in the periplasm and on the cell surface. The N2O accumulation was lower in the treatment with Fe(II) and nitrate than that in the treatment with nitrate only, although the proportions of N2O and NH4+ to the reduced NO3- were low (3.25% ∼ 6.51%) at the end of incubation regardless of Fe(II) addition. The dominant bacteria varied from soils under nitrate-reducing conditions, while Fe(II) addition shaped a similar microbial community, including Dechloromonas, Azospira, and Pseudomonas. Fe(II) addition increased the relative abundance of napAB, nirS, norBC, nosZ, and nirBD genes but decreased that of narG and nrfA, suggesting that Fe(II) oxidation favored denitrification in the periplasm and NO2--to-NH4+ reduction in the cytoplasm. Dechloromonas dominated the NO2--to-N2O reduction, while Thauera mediated the periplasmic nitrate reduction and cytoplasmic NO2--to-NH4+ during Fe(II) oxidation. However, Thauera showed much lower abundance than the dominant genera, resulting in slow nitrate reduction and limited NH4+ production. These findings provide new insights into the response of denitrification and DNRA bacteria to Fe(II) oxidation and cell encrustation in anoxic environments.

Novel Insight into Microbially Mediated Nitrate-Reducing Fe(II) Oxidation by Acidovorax sp. Strain BoFeN1 Using Dual N-O Isotope Fractionation.

Microbially mediated nitrate reduction coupled with Fe(II) oxidation (NRFO) plays an important role in the Fe/N interactions in pH-neutral anoxic environments. However, the relative contributions of the chemical and microbial processes to NRFO are still unclear. In this study, N-O isotope fractionation during NRFO was investigated. The ratios of O and N isotope enrichment factors (18ε:15ε)-NO3- indicated that the main nitrate reductase functioning in Acidovorax sp. strain BoFeN1 was membrane-bound dissimilatory nitrate reductase (Nar). N-O isotope fractionation during chemodenitrification [Fe(II) + NO2-], microbial nitrite reduction (cells + NO2-), and the coupled process [cells + NO2- + Fe(II)] was explored. The ratios of (18ε:15ε)-NO2- were 0.58 ± 0.05 during chemodenitrification and -0.41 ± 0.11 during microbial nitrite reduction, indicating that N-O isotopes can be used to distinguish chemical from biological reactions. The (18ε:15ε)-NO2- of 0.70 ± 0.05 during the coupled process was close to that obtained for chemodenitrification, indicating that chemodenitrification played a more important role than biological reactions during the coupled process. The results of kinetic modeling showed that the relative contribution of chemodenitrification was 99.3% during the coupled process, which was consistent with that of isotope fractionation. This study provides a better understanding of chemical and biological mechanisms of NRFO using N-O isotopes and kinetic modeling.

Role of PPAR-related genes in chronic heart failure: evidence from large populations.

BACKGROUND: The role of PPAR signaling and its associated genes in the pathogenesis and progression of chronic heart failure (CHF) remains elusive. METHODS: We accessed the gene expression profile and relevant baseline information of CHF samples from the Gene Expression Omnibus (GEO) database, specifically from the GSE57338 project. RESULTS: From GSE57338 project, we derived the expression value of 126 PPAR-related genes. A protein-protein interaction network was then established to illustrate potential protein interactions. ClueGO analysis results revealed that these genes predominantly participate in functions such as export across plasma membrane, regulation of lipid metabolic process, fatty acid metabolism, circulatory system vascular processes, alcohol metabolism, triglyceride metabolism and regulation of lipid localization and response to nutrient. Using the cytohubba plug-in in Cytoscape, we pinpointed ACADM, PPARG and CPT2 as potential central molecules in HF pathogenesis and progression. Subsequent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis delved into the potential biological role of these three genes in CHF. Immune infiltration analysis suggested that the infiltration level of neutrophils and M2 macrophages might be notably influenced by these genes, thereby playing a role in the CHF mechanism. CONCLUSIONS: Our research provides a comprehensive insight into the significance of PPAR associated genes in CHF development. Notably, the genes ACADM, PPARG and CPT2 emerged as potential targets for clinical interventions.

Current and Potential Applications of Atmospheric Cold Plasma in the Food Industry.

The cost-effectiveness and high efficiency of atmospheric cold plasma (ACP) incentivise researchers to explore its potentials within the food industry. Presently, the destructive nature of this nonthermal technology can be utilised to inactivate foodborne pathogens, enzymatic ripening, food allergens, and pesticides. However, by adjusting its parameters, ACP can also be employed in other novel applications including food modification, drying pre-treatment, nutrient extraction, active packaging, and food waste processing. Relevant studies were conducted to investigate the impacts of ACP and posit that reactive oxygen and nitrogen species (RONS) play the principal roles in achieving the set objectives. In this review article, operations of ACP to achieve desired results are discussed. Moreover, the recent progress of ACP in food processing and safety within the past decade is summarised while current challenges as well as its future outlook are proposed.

Mitigating the allergenicity of peanut allergen Ara h 1 by cold atmospheric pressure argon plasma jet.

BACKGROUND: Peanut allergy is recognized as a major food allergy that triggers severe and even fatal symptoms. Avoidance of peanuts in the diet is the main option for current safety management. Processing techniques reducing peanut allergenicity are required to develop other options. Cold plasma is currently considered as a novel non-thermal approach to alter protein structure and has the potential to alleviate immunoreactivity of protein allergen. RESULTS: The application of a cold argon plasma jet to peanut protein extract could reduce the amount of a 64 kDa protein band corresponding to a major peanut allergen Ara h 1 using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but the overall protein size distribution did not change significantly. A decrease in peanut protein solubility was a possible cause that led to the loss of protein content in the soluble fraction. Immunoblotting and enzyme-linked immunosorbent assay elucidated that the immunoreactivity of Ara h 1 was significantly decreased with the time treated with plasma. Ara h 1 antigenicity reduced by 38% after five scans (approximately 3 min) of cold argon plasma jet treatment, and the reduction was up to 66% after approximately 15 min of treatment. CONCLUSION: The results indicate that cold argon plasma jet treatment could be a suitable platform for alleviating the immunoreactivity of peanut protein. This work demonstrates an efficient, compact, and rapid platform for mitigating the allergenicity of peanuts, and shows great potential for the plasma platform as a non-thermal technique in the food industry. © 2023 Society of Chemical Industry.

Investigation of the physicochemical properties of the thin slices of dried pork meat paper mixed with squid.

Globally, the Peruvian squid (Dosidicus gigas) has the highest productivity among squid species. However, due to its high-water content and astringent taste, it has limited fresh food value. This study used Peruvian squid meat as the primary material to prepare thin slices of dried squid meat paper mixed with pork. Here, different proportions (20, 40, 60, 80, and 100%, while 0% as the control group) of squid surimi have used to mix with pork for the meat paper preparation and the changes in physicochemical properties, microstructure, and sensory evaluation were analyzed. The results showed that the total volatile basic nitrogen (TVB-N) contents increased with the storage period, where 20% squid surimi substitution had the lowest TVB-N content. The 20% squid surimi substitution group had the highest expansion rate, the lowest peroxide value (PV), and moisture content. The food-borne microorganisms (E. coli, coliforms, and Salmonella spp.) were within the legal limits or negative. Hardness and crispiness, 20-40% squid surimi substitution were closely similar to the control group. This study has provided an effective investigation of the possibility of expanding the utilization of Peruvian squid resources by combining appropriate squid surimi with minced pork for high-quality thin slices of dried meat paper.

Disrupted cellular calcium homeostasis is responsible for Aß-induced learning and memory damage and lifespan shortening in a model of Aß transgenic fly.

Accumulated Aß is one of the hallmarks of Alzheimer's disease. Although accumulated results from in vivo and in vitro studies have shown that accumulated Aß causes learning and memory deficit, cell death, and lifespan reduction, the underlying mechanism remains elusive. In neurons, calcium dynamics is regulated by voltage-gated calcium channel (VGCC) and endoplasmic reticulum and is important for neuron survival and formation of learning and memory. The current study employs in vivo genetics to reveal the role of calcium regulation systems in Aß-induced behavioral damage. Our data shows that although increased VGCC improves learning and memory in Aß42 flies, reduction of VGCC and Inositol trisphosphate receptors extends Aß42 flies' lifespan and improves cell viability. The complex role of calcium regulation systems in Aß-induced damage suggests that the imbalance of calcium dynamic is one of the main factors to trigger learning and memory deficit and cell death in the disease.

Applications of atmospheric cold plasma in agricultural, medical, and bioprocessing industries.

Atmospheric cold plasma (ACP) is a nonthermal technology that is extensively used in several industries. Within the scopes of engineering and biotechnology, some notable applications of ACP include waste management, material modification, medicine, and agriculture. Notwithstanding numerous applications, ACP still encounters a number of challenges such as diverse types of plasma generators and sizes, causing standardization challenges. This review focuses on the uses of ACP in engineering and biotechnology sectors in which the innovation can positively impact the operation process, enhance safety, and reduce cost. Additionally, its limitations are examined. Since ACP is still in its nascent stage, the review will also propose potential research opportunities that can help scientists gain more insights on the technology. KEY POINTS: • ACP technology has been used in agriculture, medical, and bioprocessing industries. • Chemical study on the reactive species is crucial to produce function-specific ACP. • Different ACP devices and conditions still pose standardization problems.

Assessing clinical reasoning ability in fourth-year medical students via an integrative group history-taking with an individual reasoning activity.

BACKGROUND: The most important factor in evaluating a physician's competence is strong clinical reasoning ability, leading to correct principal diagnoses. The process of clinical reasoning includes history taking, physical examinations, validating medical records, and determining a final diagnosis. In this study, we designed a teaching activity to evaluate the clinical reasoning competence of fourth-year medical students. METHODS: We created five patient scenarios for our standardized patients, including hemoptysis, abdominal pain, fever, anemia, and chest pain. A group history-taking with individual reasoning principles was implemented to teach and evaluate students' abilities to take histories, document key information, and arrive at the most likely diagnosis. Residents were trained to act as teachers, and a post-study questionnaire was employed to evaluate the students' satisfaction with the training activity. RESULTS: A total of 76 students, five teachers, and five standardized patients participated in this clinical reasoning training activity. The average history-taking score was 64%, the average key information number was 7, the average diagnosis number was 1.1, and the average correct diagnosis rate was 38%. Standardized patients presenting with abdominal pain (8.3%) and anemia (18.2%) had the lowest diagnosis rates. The scenario of anemia presented the most difficult challenge for students in history taking (3.5/5) and clinical reasoning (3.5/5). The abdominal pain scenario yielded even worse results (history taking: 2.9/5 and clinical reasoning 2.7/5). We found a correlation in the clinical reasoning process between the correct and incorrect most likely diagnosis groups (group history-taking score, p = 0.045; key information number, p = 0.009 and diagnosis number, p = 0.004). The post-study questionnaire results indicated significant satisfaction with the teaching program (4.7/5) and the quality of teacher feedback (4.9/5). CONCLUSIONS: We concluded that the clinical reasoning skills of fourth-year medical students benefited from this training course, and the lower correction of the most likely diagnosis rate found with abdominal pain, anemia, and fever might be due to a system-based teaching modules in fourth-year medical students; cross-system remedial reasoning auxiliary training is recommended for fourth-year medical students in the future.

Efficacy and safety of gastric peroral endoscopic myotomy (G-POEM) for refractory gastroparesis: 3-year follow up results.

BACKGROUND/PURPOSE: Gastroparesis is a common but easily overlooked disease. Gastric peroral endoscopic myotomy (G-POEM) is one of the third-space endoscopy techniques to treat gastroparesis. In this study, we aimed to evaluate the efficacy and safety of G-POEM for patients with refractory gastroparesis. METHODS: Between December 2017 and 2020, we consecutively enrolled patients with gastroparesis who failed after the administration of several kinds of medication and repeated admission for nutritional support. All patients underwent gastric emptying scintigraphy and answered a questionnaire on Gastroparesis Cardinal Symptom Index (GCSI). Demographic data, endoscopic procedure, and post procedural outcome were analyzed. RESULTS: A total of 11 (9 women and 2 men) patients with refractory gastroparesis (nine with diabetes mellitus, one systemic lupus erythematosus, and one idiopathic) were enrolled. The mean (±standard deviation (SD)) procedure time was 61.82 (±18.99) min with technical and clinical success rates of 100% and 81.82%, respectively. A statistically significant improvement was observed in the clinical severity (mean GCSI score 36.00 vs. 14.73, p < 0.0001) and gastric emptying time (mean T1/2 341.92 vs. 65.92 min, p = 0.016) after G-POEM. Hospital stay was 7.18 (±4.49) days without mortality. Complications included 4 (36.36%) patients with self-limited postprocedural abdominal pain and 3 (27.27%) patients with intra-procedural pneumoperitoneum. During the mean follow-up period of 554.36 days, one (9.09%) patient had relapsed clinical symptoms after 6 months. CONCLUSION: G-POEM is an efficient and safe pylorus-directed endoscopic therapy for refractory gastroparesis with promising results.

Production of Siamenoside I and Mogroside IV from Siraitia grosvenorii Using Immobilized ß-Glucosidase.

Siraitia grosvenorii is a type of fruit used in traditional Chinese medicine. Previous studies have shown that the conversion of saponins was often carried out by chemical hydrolysis, which can be problematic because of the environmental hazards it may cause and the low yield it produces. Therefore, the purpose of this study is to establish a continuous bioreactor with immobilized enzymes to produce siamenoside I and mogroside IV. The results show that the immobilization process of ß-glucosidase exhibited the best relative activity with a glutaraldehyde (GA) concentration of 1.5%, carrier activation time of 1 h and binding enzyme time of 12 h. After the immobilization through GA linkage, the highest relative activity of ß-glucosidase was recorded through the reaction with the substrate at 60 °C and pH 5. Subsequently, the glass microspheres with immobilized ß-glucosidase were filled into the reactor to maintain the optimal active environment, and the aqueous solution of Siraitia grosvenorii extract was introduced by controlling the flow rate. The highest concentration of siamenoside I and mogroside IV were obtained at a flow rate of 0.3 and 0.2 mL/min, respectively. By developing this immobilized enzyme system, siamenoside I and mogroside IV can be prepared in large quantities for industrial applications.