Metabolic reprogramming based on RNA sequencing of gemcitabine-resistant cells reveals the FASN gene as a therapeutic for bladder cancer.

Bladder cancer (BLCA) is the most frequent malignant tumor of the genitourinary system. Postoperative chemotherapy drug perfusion and chemotherapy are important means for the treatment of BLCA. However, once drug resistance occurs, BLCA develops rapidly after recurrence. BLCA cells rely on unique metabolic rewriting to maintain their growth and proliferation. However, the relationship between the metabolic pattern changes and drug resistance in BLCA is unclear. At present, this problem lacks systematic research. In our research, we identified and analyzed resistance- and metabolism-related differentially expressed genes (RM-DEGs) based on RNA sequencing of a gemcitabine-resistant BLCA cell line and metabolic-related genes (MRGs). Then, we established a drug resistance- and metabolism-related model (RM-RM) through regression analysis to predict the overall survival of BLCA. We also confirmed that RM-RM had a significant correlation with tumor metabolism, gene mutations, tumor microenvironment, and adverse drug reactions. Patients with a high drug resistance- and metabolism-related risk score (RM-RS) showed more active lipid synthesis than those with a low RM-RS. Further in vitro and in vivo studies were implemented using Fatty Acid Synthase (FASN), a representative gene, which promotes gemcitabine resistance, and its inhibitor (TVB-3166) that can reverse this resistance effect.

Cellular senescence and metabolic reprogramming model based on bulk/single-cell RNA sequencing reveals PTGER4 as a therapeutic target for ccRCC.

Clear cell renal cell carcinoma (ccRCC) is the prevailing histological subtype of renal cell carcinoma and has unique metabolic reprogramming during its occurrence and development. Cell senescence is one of the newly identified tumor characteristics. However, there is a dearth of methodical and all-encompassing investigations regarding the correlation between the broad-ranging alterations in metabolic processes associated with aging and ccRCC. We utilized a range of analytical methodologies, such as protein‒protein interaction network analysis and least absolute shrinkage and selection operator (LASSO) regression analysis, to form and validate a risk score model known as the senescence-metabolism-related risk model (SeMRM). Our study demonstrated that SeMRM could more precisely predict the OS of ccRCC patients than the clinical prognostic markers in use. By utilizing two distinct datasets of ccRCC, ICGC-KIRC (the International Cancer Genome Consortium) and GSE29609, as well as a single-cell dataset (GSE156632) and real patient clinical information, and further confirmed the relationship between the senescence-metabolism-related risk score (SeMRS) and ccRCC patient progression. It is worth noting that patients who were classified into different subgroups based on the SeMRS exhibited notable variations in metabolic activity, immune microenvironment, immune cell type transformation, mutant landscape, and drug responsiveness. We also demonstrated that PTGER4, a key gene in SeMRM, regulated ccRCC cell proliferation, lipid levels and the cell cycle in vivo and in vitro. Together, the utilization of SeMRM has the potential to function as a dependable clinical characteristic to increase the accuracy of prognostic assessment for patients diagnosed with ccRCC, thereby facilitating the selection of suitable treatment strategies.

Exploring factors influencing delayed first antibiotic treatment for suspected early-onset sepsis in preterm newborns: a study before quality improvement initiative.

BACKGROUND: Early-onset sepsis (EOS) is a serious illness that affects preterm newborns, and delayed antibiotic initiation may increase the risk of adverse outcomes. PURPOSE: The objective of this study was to examine the present time of antibiotic administration in preterm infants with suspected EOS and the factors that contribute to delayed antibiotic initiation. METHODS: In this retrospective study in China, a total of 82 early preterm infants with suspected EOS between December 2021 and March 2023 were included. The study utilized a linear regression analytical approach to identify independent factors that contribute to delayed antibiotic administration. RESULTS: The mean gestational age and birth weight of the study population were 29.1 ± 1.4 weeks and 1265.7 ± 176.8 g, respectively. The median time of initial antibiotic administration was 3.8 (3.1-5.0) hours. Linear regression revealed that severe respiratory distress syndrome (RDS) (ß = 0.07, P = 0.013), penicillin skin test (PST) timing (ß = 0.06, P < 0.001) and medical order timing (ß = 0.04, P = 0.017) were significantly associated with the initial timing of antibiotic administration. CONCLUSIONS: There is an evident delay in antibiotic administration in preterm infants with suspected EOS in our unit. Severe RDS, PST postponement and delayed medical orders were found to be associated with the delayed use of antibiotics, which will be helpful for quality improvement efforts in the neonatal intensive care unit (NICU).

Exploration and Insights on Topology Adjustment of Giant Heterometallic Cages Featuring Inorganic Skeletons Assisted by Machine Learning.

Inorganic molecular cages are emerging multifunctional molecular-based platforms with the unique merits of rigid skeletons and inherited properties from constituent metal ions. However, the sensitive coordination bonds and vast synthetic space have limited their systematic exploration. Herein, two giant cage-like clusters featuring the organic ligand-directed inorganic skeletons of Ni4[La74Ni104(IDA)96(OH)184(C2O4)12(H2O)76]·(NO3)38·(H2O)120 (La74Ni104, 5 × 5 × 3 - C2O4) and [La84Ni132(IDA)108(OH)168(C2O4)24(NO3)12(H2O)116]·(NO3)72·(H2O)296 (La84Ni132, 5 × 5 × 5 - C2O4) were discovered by a high-throughput synthetic search. With the assistance of machine learning analysis of the experimental data, phase diagrams of the two clusters in a four-parameter synthetic space were depicted. The effect of alkali, oxalate, and other parameters on the formation of clusters and the mechanism regulating the size of two n × m × l clusters were elucidated. This work uses high-throughput synthesis and machine learning methods to improve the efficiency of 3d-4f cluster discovery and finds the highest-nuclearity 3d-4f cluster to date by regulating the size of the n × m × l inorganic cages through oxalate ions, which pushes the synthetic methodology study on elusive inorganic giant cages in a significantly systematic way.

A Randomized Clinical Trial to Compare Three Different Methods for Estimating Orogastric Tube Insertion Length in Newborns: A Single-Center Experience in China.

Background: Orogastric (OG) and nasogastric (NG) tubes are frequently used in the NICU. Obtaining a relatively accurate estimated length before insertion could significantly reduce complications. While previous studies have mainly focused on the NG tube, OG tubes are more commonly used in China. Purpose: The objective was to determine whether there were differences in the rate of accurate placement among the adapted nose-ear-xiphoid (NEX) method, nose-ear-midway to the umbilicus (NEMU) method, and weight-based (WB) equation in estimating the OG tube insertion distance. Methods: A randomized, controlled, open-label clinical trial to compare the three methods was conducted in a single center. After enrollment, newborns were randomly assigned into three groups. By radiological assessment, the anatomical region for OG tube placement was analyzed. The primary metric was the tip within the gastric body, and the second metric was strictly accurate placement defined as the tube was not looped back within the stomach and the end was located more than 2 cm but less than 5 cm into the stomach, referred to as T10. Results: This study recruited 156 newborns with the majority being preterm infants (n = 96; 61.5 percent), with an average birth weight of 2,200.8 ± 757.8 g. For the WB equation, 96.2 percent (50 cases) of the OG tubes were placed within the stomach, and the rates were 78.8 percent (41 cases) in the adapted NEX and NEMU methods. The strictly accurate placement rates were highest for the WB equation at 80.8 percent (42/52), followed by the adapted NEX method at 65.4 percent (34/52), and the NEMU method at 57.7 percent (30/52). Conclusion: The WB equation for estimating the insertion depth of the OG tube in newborn infants resulted in more precise placement compared to the adapted NEX and NEMU methods.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China. / è¶ æœªæˆç†ŸåŒèƒŽå„¿ä¸´åºŠæ•‘æ²»ç»“å±€åŠå˜åŒ–åˆ†æžï¼šä¸€é¡¹å¹¿ä¸œçœå¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Oxidative Polymerization in Living Cells.

Intracellular polymerization is an emerging technique that can potentially modulate cell behavior, but remains challenging because of the complexity of the cellular environment. Herein, taking advantage of the chemical properties of organotellurides and the intracellular redox environment, we develop a novel oxidative polymerization reaction that can be conducted in cells without external stimuli. We demonstrate that this polymerization reaction is triggered by the intracellular reactive oxygen species (ROS), thus selectively proceeding in cancer cells and inducing apoptosis via a unique self-amplification mechanism. The polymerization products are shown to disrupt intracellular antioxidant systems through interacting with selenoproteins, leading to greater oxidative stress that would further the oxidative polymerization and eventually activate ROS-related apoptosis pathways. The selective anticancer efficacy and biosafety of our strategy are proven both in vitro and in vivo. Ultimately, this study enables a new possibility for chemists to manipulate cellular proliferation and apoptosis through artificial chemical reactions.

Machine-Learning-Guided Discovery and Optimization of Additives in Preparing Cu Catalysts for CO2 Reduction.

Discovery and optimization of new catalysts can be potentially accelerated by efficient data analysis using machine-learning (ML). In this paper, we record the process of searching for additives in the electrochemical deposition of Cu catalysts for CO2 reduction (CO2RR) using ML, which includes three iterative cycles: "experimental test; ML analysis; prediction and redesign". Cu catalysts are known for CO2RR to obtain a range of products including C1 (CO, HCOOH, CH4, CH3OH) and C2+ (C2H4, C2H6, C2H5OH, C3H7OH). Subtle changes in morphology and surface structure of the catalysts caused by additives in catalyst preparation can lead to dramatic shifts in CO2RR selectivity. After several ML cycles, we obtained catalysts selective for CO, HCOOH, and C2+ products. This catalyst discovery process highlights the potential of ML to accelerate material development by efficiently extracting information from a limited number of experimental data.

Neighboring Zn-Zr Sites in a Metal-Organic Framework for CO2 Hydrogenation.

ZrZnOx is active in catalyzing carbon dioxide (CO2) hydrogenation to methanol (MeOH) via a synergy between ZnOx and ZrOx. Here we report the construction of Zn2+-O-Zr4+ sites in a metal-organic framework (MOF) to reveal insights into the structural requirement for MeOH production. The Zn2+-O-Zr4+ sites are obtained by postsynthetic treatment of Zr6(µ3-O)4(µ3-OH)4 nodes of MOF-808 by ZnEt2 and a mild thermal treatment to remove capping ligands and afford exposed metal sites for catalysis. The resultant MOF-808-Zn catalyst exhibits >99% MeOH selectivity in CO2 hydrogenation at 250 °C and a high space-time yield of up to 190.7 mgMeOH gZn-1 h-1. The catalytic activity is stable for at least 100 h. X-ray absorption spectroscopy (XAS) analyses indicate the presence of Zn2+-O-Zr4+ centers instead of ZnmOn clusters. Temperature-programmed desorption (TPD) of hydrogen and H/D exchange tests show the activation of H2 by Zn2+ centers. Open Zr4+ sites are also critical, as Zn2+ centers supported on Zr-based nodes of other MOFs without open Zr4+ sites fail to produce MeOH. TPD of CO2 reveals the importance of bicarbonate decomposition under reaction conditions in generating open Zr4+ sites for CO2 activation. The well-defined local structures of metal-oxo nodes in MOFs provide a unique opportunity to elucidate structural details of bifunctional catalytic centers.

Single-course antenatal corticosteroids is related to faster growth in very-low-birth-weight infant.

BACKGROUND: Antenatal corticosteroids (ACS) treatment is critical to support survival and lung maturation in preterm infants, however, its effect on feeding and growth is unclear. Prior preterm delivery, it remains uncertain whether ACS treatment should be continued if possible (repeated course ACS), until a certain gestational age is reached. We hypothesized that the association of single-course ACS with feeding competence and postnatal growth outcomes might be different from that of repeated course ACS in very-low-birth-weight preterm infants. METHODS: A multicenter retrospective cohort study was conducted in very-low-birth-weight preterm infants born at 23-37 weeks' gestation in South China from 2011 to 2014. Data on growth, nutritional and clinical outcomes were collected. Repeated course ACS was defined in this study as two or more courses ACS (more than single-course). Infants were stratified by gestational age (GA), including GA < 28 weeks, 28 weeks ≤ GA < 32 weeks and 32 weeks ≤ GA < 37 weeks. Multiple linear regression and multilevel model were applied to analyze the association of ACS with feeding and growth outcomes. RESULTS: A total of 841 infants were recruited. The results, just in very-low-birth-weight preterm infants born at 28-32 weeks' gestation, showed both single and repeated course of ACS regimens had shorter intubated ventilation time compared to non-ACS regimen. Single-course ACS promoted the earlier application of amino acid and enteral nutrition, and higher rate of weight increase (15.71; 95%CI 5.54-25.88) than non-ACS after adjusting for potential confounding factors. No associations of repeated course ACS with feeding, mean weight and weight increase rate were observed. CONCLUSIONS: Single-course ACS was positively related to feeding and growth outcomes in very-low-birth-weight preterm infants born at 28-32 weeks' gestation. However, the similar phenomenon was not observed in the repeated course of ACS regimen.

Short-term outcomes of extremely preterm infants at discharge: a multicenter study from Guangdong province during 2008-2017.

BACKGROUND: An increasing number of extremely preterm (EP) infants have survived worldwide. However, few data have been reported from China. This study was designed to investigate the short-term outcomes of EP infants at discharge in Guangdong province. METHODS: A total of 2051 EP infants discharged from 26 neonatal intensive care units during 2008-2017 were enrolled. The data from 2008 to 2012 were collected retrospectively, and from 2013 to 2017 were collected prospectively. Their hospitalization records were reviewed. RESULTS: During 2008-2017, the mean gestational age (GA) was 26.68 ± 1.00 weeks and the mean birth weight (BW) was 935 ± 179 g. The overall survival rate at discharge was 52.5%. There were 321 infants (15.7%) died despite active treatment, and 654 infants (31.9%) died after medical care withdrawal. The survival rates increased with advancing GA and BW (p < 0.001). The annual survival rate improved from 36.2% in 2008 to 59.3% in 2017 (p < 0.001). EP infants discharged from hospitals in Guangzhou and Shenzhen cities had a higher survival rate than in others (p < 0.001). The survival rate of EP infants discharged from general hospitals was lower than in specialist hospitals (p < 0.001). The major complications were neonatal respiratory distress syndrome, 88.0% (1804 of 2051), bronchopulmonary dysplasia, 32.3% (374 of 1158), retinopathy of prematurity (any grade), 45.1% (504 of 1117), necrotizing enterocolitis (any stage), 10.1% (160 of 1588), intraventricular hemorrhages (any grade), 37.4% (535 of 1431), and blood culture-positive nosocomial sepsis, 15.7% (250 of 1588). The multivariate logistic regression analysis indicated that improved survival of EP infants was associated with discharged from specialist hospitals, hospitals located in high-level economic development region, increasing gestational age, increasing birth weight, antenatal steroids use and a history of premature rupture of membranes. However, twins or multiple births, Apgar ≤7 at 5 min, cervical incompetence, and decision to withdraw care were associated with decreased survival. CONCLUSIONS: Our study revealed the short-term outcomes of EP infants at discharge in China. The overall survival rate was lower than the developed countries, and medical care withdrawal was a serious problem. Nonetheless, improvements in care and outcomes have been made annually.

Association of Heparin-binding EGF-like Growth Factor Polymorphisms With Necrotizing Enterocolitis in Preterm Infants.

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) protects the intestines from injury in experimental necrotizing enterocolitis (NEC). We hypothesized that polymorphisms in the HB-EGF gene lead to low HB-EGF production in peripheral blood and increased risk of NEC in the Chinese Han population. To test this hypothesis, 30 NEC patients and 80 control subjects were selected. Five HB-EGF single-nucleotide polymorphisms (SNPs) and its plasma levels were measured by genotyping and enzyme-linked immunosorbent assay, respectively. Only 1 out of the 5 SNPs showed a notable result. The notable SNP (rs4912711) was associated with NEC in its minor allele frequency and its "G/T" genotype distribution. In addition, plasma HB-EGF levels were reduced especially the "G/T" genotype in NEC patients. Our data suggest that if validated in larger studies screening for HB-EGF SNPs/genotypes and plasma levels may be useful as a risk factor for NEC in the future.

NPHS2 variation in Chinese southern infants with late steroid-resistant nephrotic syndrome.

Abstract NPHS2 mutations are responsible for autosomal recessive familial steroid-resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis (FSGS), which is characterized by early childhood onset and rapid progression to chronic renal insufficiency. This gene mutation is also responsible for an adolescent onset form of autosomal recessive familial FSGS with heavy proteinuria. Many infants with late steroid-resistant nephrotic syndrome (late SRNS) are prone to an implicated clinical and therapeutic course. The etiopathogenesis and the long-term prognosis of late SRNS remain obscure. Considering the similar steroid resistance between late and initial SRNS, analysis of NPHS2 variation was performed in 70 sporadic Chinese infants with late SRNS and 70 controls in the present study to investigate the possible role of NPHS2 gene in late SRNS. The variation analysis revealed three polymorphisms (288C > T heterozygous in exon 2, 954T > C heterozygous and homozygous, and 1038A > G heterozygous in exon 8) in 22 out of 70 patients studied. In conclusion, NPHS2 gene mutations are not a major cause of chronic renal insufficiency caused by late SRNS in Chinese southern infants.

m6A-Mediated Induction of 7-Dehydrocholesterol Reductase Stimulates Cholesterol Synthesis and cAMP Signaling to Promote Bladder Cancer Metastasis.

Dysregulation of cholesterol homeostasis occurs in multiple types of tumors and promotes cancer progression. Investigating the specific processes that induce abnormal cholesterol metabolism could identify therapeutic targets to improve cancer treatment. In this investigation, we observed upregulation of 7-dehydrocholesterol reductase (DHCR7), a vital enzyme involved in the synthesis of cholesterol, within bladder cancer (BC) tissues in comparison to normal tissues, which was correlated with increased BC metastasis. Increased expression of DHCR7 in BC was attributed to decreased mRNA degradation mediated by YTHDF2. Loss or inhibition of DHCR7 reduced BC cell invasion in vitro and metastasis in vivo. Mechanistically, DHCR7 promoted BC metastasis by activating the cAMP/PKA/FAK pathway. Specifically, DHCR7 increased cAMP levels by elevating cholesterol content in lipid rafts, thereby facilitating the transduction of signaling pathways mediated by cAMP receptors. DHCR7 additionally enhanced the cAMP signaling pathway by reducing the concentration of 7-DHC and promoting the transcription of the G protein-coupled receptor GIPR. Overall, these findings demonstrate that DHCR7 plays an important role in BC invasion and metastasis by modulating cholesterol synthesis and cAMP signaling. Furthermore, inhibition of DHCR7 shows promise as a viable therapeutic strategy for suppressing BC invasion and metastasis.

MLatom 3: A Platform for Machine Learning-Enhanced Computational Chemistry Simulations and Workflows.

Machine learning (ML) is increasingly becoming a common tool in computational chemistry. At the same time, the rapid development of ML methods requires a flexible software framework for designing custom workflows. MLatom 3 is a program package designed to leverage the power of ML to enhance typical computational chemistry simulations and to create complex workflows. This open-source package provides plenty of choice to the users who can run simulations with the command-line options, input files, or with scripts using MLatom as a Python package, both on their computers and on the online XACS cloud computing service at XACScloud.com. Computational chemists can calculate energies and thermochemical properties, optimize geometries, run molecular and quantum dynamics, and simulate (ro)vibrational, one-photon UV/vis absorption, and two-photon absorption spectra with ML, quantum mechanical, and combined models. The users can choose from an extensive library of methods containing pretrained ML models and quantum mechanical approximations such as AIQM1 approaching coupled-cluster accuracy. The developers can build their own models using various ML algorithms. The great flexibility of MLatom is largely due to the extensive use of the interfaces to many state-of-the-art software packages and libraries.

Visualizing Chain Growth of Polytelluoxane via Polymerization Induced Emission.

Visualizing polymer chain growth is always a hot topic for tailoring structure-function properties in polymer chemistry. However, current characterization methods are limited in their ability to differentiate the degree of polymerization in real-time without isolating the samples from the reaction vessel, let alone to detect insoluble polymers. Herein, a reliable relationship is established between polymer chain growth and fluorescence properties through polymerization induced emission. (TPE-C2)2 -Te is used to realize in situ oxidative polymerization, leading to the aggregation of fluorophores. The relationship between polymerization degree of growing polytelluoxane (PTeO) and fluorescence intensity is constructed, enabling real-time monitoring of the polymerization reaction. More importantly, this novel method can be further applied to the observation of the polymerization process for growing insoluble polymer via surface polymerization. Therefore, the development of visualization technology will open a new avenue for visualizing polymer chain growth in real-time, regardless of polymer solubility.

Intracellular Hyperbranched Polymerization for Circumventing Cancer Drug Resistance.

Polymerization inside living cells provides chemists with a multitude of possibilities to modulate cell activities. Considering the advantages of hyperbranched polymers, such as a large surface area for target sites and multilevel branched structures for resistance to the efflux effect, we reported a hyperbranched polymerization in living cells based on the oxidative polymerization of organotellurides and intracellular redox environment. The intracellular hyperbranched polymerization was triggered by reactive oxygen species (ROS) in the intracellular redox microenvironment, effectively disrupting antioxidant systems in cells by an interaction between Te (+4) and selenoproteins, thus inducing selective apoptosis of cancer cells. Importantly, the obtained hyperbranched polymer aggregated into branched nanostructures in cells, which could effectively evade drug pumps and decrease drug efflux, ensuring the polymerization for persistent treatment. Finally, in vitro and in vivo studies confirmed that our strategy presented selective anticancer efficacy and well biosafety. This approach provides a way for intracellular polymerization with desirable biological applications to regulate cell activities.

Interpretable Machine Learning of Two-Photon Absorption.

Molecules with strong two-photon absorption (TPA) are important in many advanced applications such as upconverted laser and photodynamic therapy, but their design is hampered by the high cost of experimental screening and accurate quantum chemical (QC) calculations. Here a systematic study is performed by collecting an experimental TPA database with ≈900 molecules, analyzing with interpretable machine learning (ML) the key molecular features explaining TPA magnitudes, and building a fast ML model for predictions. The ML model has prediction errors of similar magnitude compared to experimental and affordable QC methods errors and has the potential for high-throughput screening as additionally validated with the new experimental measurements. ML feature analysis is generally consistent with common beliefs which is quantified and rectified. The most important feature is conjugation length followed by features reflecting the effects of donor and acceptor substitution and coplanarity.

Dynamic changes of the gut microbial colonization in preterm infants with different time points after birth.

Risks associated with preterm birth are unevenly distributed across all gestations. At earlier gestational ages, complications such as necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) conditions are significantly more common and are associated with a shift in the composition of the gut microbiome. Conventional bacterial culture techniques demonstrate that the colonization of the gut microbiota of preterm infants differs significantly from that of healthy-term infants. The current study aimed to investigate the impact of preterm infancy on the dynamic changes of fecal microbiota in preterm infants at different time points (1, 7, 14, 21, 28, and 42 days) after birth. We selected 12 preterm infants hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2017. A total of 130 fecal specimens from preterm infants were analyzed using 16S rRNA gene sequencing. We found that the colonization process of fecal microbiota in preterm infants is highly dynamic at different time points after birth, i.e., Exiguobacterium, Acinetobacter, and Citrobacter showed a declining abundance pattern with the advancement of age, while the bacterial groups of Enterococcus (Klebsiella and Escherichia coli) gradually grew and became the main microbiota during the development of fecal microbiota in preterm infants at the age of 42 days. Furthermore, the colonization of intestinal Bifidobacteria in preterm infants was relatively late and did not rapidly become the predominant microbiota. Moreover, the results also showed the presence of Chryseobacterium bacterial group, whose colonization was different in different time point groups. Conclusively, our findings deepen our comprehension and offer new perspectives on targeting particular bacteria in the treatment of preterm infants at different time points after birth.

The Role of Albumin in the Diagnosis of Neonatal Sepsis Over the Last 11 Years: A Retrospective Study.

Background: There are many difficulties and uncertainties in the early diagnosis of neonatal sepsis. The aim of this study was to determine whether albumin (ALB) is useful for the early diagnosis of neonatal sepsis using ALB, C-reactive protein (CRP) and procalcitonin (PCT) together. Methods: ALB, CRP, PCT and white blood cell (WBC) data from 732 patients with neonatal sepsis and 1317 neonatal infection patients hospitalized in Foshan Maternal and Child Health Hospital from 2011 to 2022 were collected. Receiver operating characteristic (ROC) and logistic regression analyses were performed to assess the diagnostic value of ALB, CRP, PCT and the WBC count for neonatal sepsis. The roles of ALB, CRP, PCT and the WBC count in the diagnosis of neonatal sepsis were analysed by using subject working characteristics (ROC) and areas under the curve (AUCs), and the variables were combined to determine which combination had the best diagnostic efficacy. Results: In the sepsis group, the ALB, CRP, and PCT levels and the WBC count were significantly higher than those in the infection group (P<0.001). In all infants, the sensitivities and specificities of ALB, CRP, PCT, and WBC count were 0.411, 0.596, 0.483 and 0.411, respectively, and 0.833, 0.846, 0.901 and 0.796, respectively. With a sensitivity of 0.646, a specificity of 0.929, and an AUC of 0.834, the best combination was that of ALB, CRP, and PCT, which was better than that of CRP + PCT, CRP + ALB and PCT + ALB. Conclusion: In neonatal sepsis, in the absence of blood culture results, the combination of ALB, CRP, and PCT is more reliable than CRP, PCT, or CRP+PCT alone. These results suggest that ALB is a useful inflammatory biomarker for the early diagnosis of neonatal sepsis, and can improve the diagnostic efficiency.