Cultivated Enterococcus faecium B6 from children with obesity promotes nonalcoholic fatty liver disease by the bioactive metabolite tyramine.

Gut microbiota plays an essential role in nonalcoholic fatty liver disease (NAFLD). However, the contribution of individual bacterial strains and their metabolites to childhood NAFLD pathogenesis remains poorly understood. Herein, the critical bacteria in children with obesity accompanied by NAFLD were identified by microbiome analysis. Bacteria abundant in the NAFLD group were systematically assessed for their lipogenic effects. The underlying mechanisms and microbial-derived metabolites in NAFLD pathogenesis were investigated using multi-omics and LC-MS/MS analysis. The roles of the crucial metabolite in NAFLD were validated in vitro and in vivo as well as in an additional cohort. The results showed that Enterococcus spp. was enriched in children with obesity and NAFLD. The patient-derived Enterococcus faecium B6 (E. faecium B6) significantly contributed to NAFLD symptoms in mice. E. faecium B6 produced a crucial bioactive metabolite, tyramine, which probably activated PPAR-γ, leading to lipid accumulation, inflammation, and fibrosis in the liver. Moreover, these findings were successfully validated in an additional cohort. This pioneering study elucidated the important functions of cultivated E. faecium B6 and its bioactive metabolite (tyramine) in exacerbating NAFLD. These findings advance the comprehensive understanding of NAFLD pathogenesis and provide new insights for the development of microbe/metabolite-based therapeutic strategies.

Integrative metabolomics highlights gut microbiota metabolites as novel NAFLD-related candidate biomarkers in children.

Altered gut microbiota and metabolites are important for non-alcoholic fatty liver disease (NAFLD) in children. We aimed to comprehensively examine the effects of gut metabolites on NAFLD progression. We performed integrative metabolomics (untargeted discovery and targeted validation) analysis of non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and obesity in children. Fecal samples were collected from 75 subjects in the discovery cohort (25 NAFL, 25 NASH, and 25 obese control children) and 145 subjects in an independent validation cohort (53 NAFL, 39 NASH, and 53 obese control children). Among 2,491 metabolites, untargeted metabolomics revealed a complete NAFLD metabolic map containing 318 increased and 123 decreased metabolites. Then, machine learning selected 65 important metabolites that can distinguish the severity of the NAFLD. Furthermore, precision-targeted metabolomics selected 5 novel gut metabolites from 20 typical metabolites. The functionality of candidate metabolites was validated in hepatocyte cell lines. In the end, this study annotated two novel elevated pathogenic metabolites (dodecanoic acid and creatinine) and a relationship between depleted protective gut microbiota (Butyricicoccus and Alistipes), increased inflammation (IL-1ß), lipid metabolism (TG), and liver function (ALT and AST). This study demonstrates the role of novel gut metabolites (dodecanoic acid and creatinine), as the fatty acid metabolism regulator contributing to NAFLD development through its influence on inflammation and liver function. IMPORTANCE: Altered gut microbiota and metabolites are a major cause of non-alcoholic fatty liver disease (NAFLD) in children. This study demonstrated a complete gut metabolic map of children with NAFLD, containing 318 increased and 123 decreased metabolites by untargeted metabolomic. Multiple validation approaches (machine learning and targeted metabolomic) selected five novel gut metabolites for targeted metabolomics, which can distinguish NAFLD status and severity. The gut microbiota (Butyricicoccus and Alistipes) and metabolites (creatinine and dodecanoic acid) were novel biomarkers associated with impaired liver function and inflammation and validated by experiments of hepatocyte cell lines. The data provide a better understanding of the importance of gut microbiota and metabolite alterations in NAFLD, which implies that the altered gut microbiota and metabolites may represent a potential target to prevent NAFLD development.

Identification of commensal gut bacterial strains with lipogenic effects contributing to NAFLD in children.

Gut microbiota is known to have a significant impact on nonalcoholic fatty liver disease (NAFLD), particularly in children with obesity. However, the specific functions of microbiota at the strain level in this population have not been fully elucidated. In this study, we successfully isolated and identified several commensal gut bacterial strains that were dominant in children with obesity and NAFLD. Among these, four novel isolates were found to have significant lipogenic effects in vitro. These strains exhibited a potential link to hepatocyte steatosis by regulating the expression of genes involved in lipid metabolism and inflammation. Moreover, a larger cohort analysis confirmed that these identified bacterial strains were enriched in the NAFLD group. The integrated analysis of these strains effectively distinguished NASH from NAFL. These four strains might serve as potential biomarkers in children with NAFLD. These findings provided new insights into the exploration of therapeutic targets for NAFLD.

A comparative analysis of Postpartum Hemorrhage incidence and influencing factors between nulliparous and multiparous women in Hunan Province, China: A multicenter retrospective cohort study.

Objectives: Postpartum hemorrhage (PPH) is a common cause of maternal death worldwide, but data on PPH incidence and influencing factors for nulliparous and multiparous women is scarce. So, the study aimed to assess the differences in PPH incidence and influencing factors between nulliparous and multiparous women. Methods: A multicenter retrospective cohort study was conducted among women who gave birth at ≥ 28 weeks of gestation in Hunan Province, China, from January 2017 to December 2018. Logistic regression assessed PPH-influencing factors, and the receiver operating characteristic curve (ROC curve) assessed the predictive performance of identified factors. Results: A total of 144,845 postpartum women were included in the study. The incidence of PPH (blood loss ≥ 500 ml) was 2.1 % and 1.7 % for nulliparous and multiparous women, respectively. Among the nulliparous and multiparous women, similar influencing factors of PPH included erythrocyte suspension transfusion before childbirth, anemia, soft-birth canal avulsion, Cesarean-section, placenta abruption, and general anesthesia administration before birth. Thrombophlebitis was associated [aOR 18.46(1.67-20.31)] with PPH among only the nulliparous women, while instrument-assisted birth [aOR 1.95(1.16-3.28)] and gestational hypertension [aOR 1.57(1.13-2.19)] were associated with PPH among only the multiparous women. The areas under the ROC-curve for the overall-cohort, nulliparous, and multiparous groups were [0.829(0.821-0.838)], [0.828(0.815-0.840)] and [0.833(0.822-0.844)], respectively. Conclusion: PPH incidence is higher among nulliparous women than among multiparous women, but influencing factors vary relatively by parity. The study findings provide new insights into the use of different approaches to PPH prevention for nulliparous and multiparous women in clinical practice.

Comparative genomic analysis and functional investigations for MCs catabolism mechanisms and evolutionary dynamics of MCs-degrading bacteria in ecology.

Microcystins (MCs) significantly threaten the ecosystem and public health. Biodegradation has emerged as a promising technology for removing MCs. Many MCs-degrading bacteria have been identified, including an indigenous bacterium Sphingopyxis sp. YF1 that could degrade MC-LR and Adda completely. Herein, we gained insight into the MCs biodegradation mechanisms and evolutionary dynamics of MCs-degrading bacteria, and revealed the toxic risks of the MCs degradation products. The biochemical characteristics and genetic repertoires of strain YF1 were explored. A comparative genomic analysis was performed on strain YF1 and six other MCs-degrading bacteria to investigate their functions. The degradation products were investigated, and the toxicity of the intermediates was analyzed through rigorous theoretical calculation. Strain YF1 might be a novel species that exhibited versatile substrate utilization capabilities. Many common genes and metabolic pathways were identified, shedding light on shared functions and catabolism in the MCs-degrading bacteria. The crucial genes involved in MCs catabolism mechanisms, including mlr and paa gene clusters, were identified successfully. These functional genes might experience horizontal gene transfer events, suggesting the evolutionary dynamics of these MCs-degrading bacteria in ecology. Moreover, the degradation products for MCs and Adda were summarized, and we found most of the intermediates exhibited lower toxicity to different organisms than the parent compound. These findings systematically revealed the MCs catabolism mechanisms and evolutionary dynamics of MCs-degrading bacteria. Consequently, this research contributed to the advancement of green biodegradation technology in aquatic ecology, which might protect human health from MCs.

Association between multimorbidity of pregnancy and adverse birth outcomes: A systemic review and meta-analysis.

Multimorbidity (≥2 co-existing conditions) in pregnancy is a significant public health issue with a rising prevalence worldwide. However, the association between pregnancy multimorbidity and adverse birth outcomes is unclear. So, this review assessed the association between pregnancy-multimorbidity and adverse birth outcomes (preterm birth, abnormal birth weight, neonatal mortality, and stillbirth). Relevant peer-reviewed papers in PubMed, Web of Science, Elsevier/ScienceDirect, and Google Scholar were systematically search from January 1990 to March 2023. We used the random-effects model to calculate the multimorbidity pooled odds ratio, quantified heterogeneity using I2 statistics, and performed subgroup and sensitivity analyses in Stata version 17. The review protocol is registered with PROSPERO (CRD42023421336). The meta-analysis included 21 observational studies involving 6,523,741 pregnant women. The overall pooled odds of pregnancy multimorbidity associated with adverse birth outcomes were 3.11(2.14-4.09), 3.76(2.56-4.96) in Europe, 3.38(1.18-5.58) in North America, and 2.94(0.78-5.09) in Asia. Pregnant women with psychological and physical multimorbidity had increased odds of 5.65(1.71-9.59) and 2.75(1.71-9.58), respectively, for adverse birth outcomes. Pregnancy multimorbidity was associated with preterm birth 4.28(2.23-6.34), large gestational age (>90 percentile) 3.33(1.50-5.17), macrosomia (≥4000 g) 2.16(0.34-3.98), and small gestational age (<10th percentile) 3.52(1.54-5.51). There is substantial variance in the odds of pregnancy multimorbidity by type of comorbidity and type of adverse birth outcome, attributed to differences in the healthcare system by geographical location. Therefore, prioritizing pregnant women with multimorbidity is crucial for effective and integrative interventions.

Dose-response associations of maternal age with pregnancy complications and multimorbidity among nulliparas and multiparas: A multicentric retrospective cohort study in southern China.

Background: Advanced maternal age is becoming an increasingly common issue worldwide, presenting substantial health risks to pregnant women. However, dose-response associations of maternal age with a comprehensive range of pregnancy complications and their multimorbidity remain unclear. Methods: We conducted a retrospective cohort study using data from China's National Maternal Near Miss Surveillance System for 2017-2018, including 18 hospitals in southern China. We included 135 274 pregnant women aged 15-54 years with a singleton birth. We used multivariable logistic regression and restricted cubic spline to examine dose-response associations between maternal age and various pregnancy complications, as well as multimorbidity. We employed the Apriori algorithm to mine the association rules among pregnancy complications and identify frequent multimorbidity patterns. Results: We found three distinct patterns of associations between maternal age and specific pregnancy complications. In relation to increasing maternal age, gestational diabetes mellitus, preeclampsia, and gestational hypertension showed nonlinear increasing trends for both nulliparas and multiparas, as did multimorbidity in nulliparas. Conversely, we observed linear increasing trends for placental previa in both nulliparas and multiparas, placental abruption in nulliparas, and multimorbidity in multiparas. Infection and severe anaemia had an approximate J-shaped curve among nulliparas, while postpartum haemorrhage exhibited a similar curve in both nulliparas and multiparas. Advanced maternal age was linked to an elevated risk of multimorbidity during pregnancy or postpartum period, exhibiting more complicated patterns. The most common multimorbidity patterns in this age group were "preeclampsia + gestational diabetes mellitus", "gestational hypertension + gestational diabetes mellitus", "infection + gestational diabetes mellitus", and "placental previa + gestational diabetes mellitus". Conclusions: Maternal age was associated with pregnancy complications and multimorbidity in three broad dose-response manners, including approximate J-shaped curves, as well as nonlinear and linear increasing trends, depending on the specific outcome and parity, which may suggest different underlying biological mechanisms. Women with advanced maternal age had a higher risk and more complicated patterns of multimorbidity during pregnancy or postpartum, suggesting that this group should be targeted for more intensive health care.

Association of Calpain10 polymorphisms with polycystic ovarian syndrome susceptibility: a systematic review and meta-analysis with trial sequential analysis.

Insulin resistance plays an important role in the pathogenesis of polycystic ovarian syndrome (PCOS). Calpain10 (CAPN10) gene was the first identified susceptibility gene for type 2 diabetes mellitus and closely related to insulin sensitivity. A lot of research attention has been attracted on the relationship between CAPN10 polymorphisms and PCOS risk, but they didn't reach a consistent conclusion. We therefore performed this systematic review and meta-analysis to assess the association of CAPN10 common variants with PCOS susceptibility. A total of 21 studies were eligible for inclusion. Meta-analyses were done for 5 variants that had at least two data sources: UCSNP-19, -43, -44, -56 and -63. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under five genetic models. Subgroup analyses by ethnicity, PCOS diagnostic criteria, and source of controls were conducted. Moreover, false-positive report probability (FPRP) test and trial sequential analysis (TSA) were performed to assess the significant associations. The results showed a possible negative association between UCSNP-19 and PCOS risk (ins/ins vs. del/del + del/ins: OR = 0.84, 95% CI: 0.72-0.98). In subgroup analyses, FPRP test indicated that noteworthy associations were observed in mixed ethnicities for UCSNP-43 (A vs. G: OR = 1.81, 95% CI: 1.17-2.79; AA + AG vs. GG: OR = 2.14, 95% CI: 1.20-3.80) and in Asians for UCSNP-44 (CC vs. TT: OR = 2.07, 95% CI: 1.21-3.51; CC vs. CT + TT: OR = 2.19, 95% CI: 1.31-3.69), but TSA plots showed that the accumulated sample sizes of these associations were insufficient to draw firm conclusions. In summary, our study suggested that UCSNP-19, UCSNP-43, and UCSNP-44 in CAPN10 gene may be involved in PCOS susceptibility. These findings warrant further studies.

Comparison of hospital delivery costs between cesarean section and natural delivery and analysis of influencing factors. / å‰–å®«äº§ä¸Žè‡ªç„¶åˆ†å¨©è€ ä½é™¢è´¹ç”¨çš„æ¯”è¾ƒä¸Žç›¸å ³å› ç´ åˆ†æž.

OBJECTIVES: The increasing costs of hospital delivery have increased the economic burden of pregnant women, and the mode of delivery is the main factor affecting the costs of hospital delivery. This study aims to explore the difference in costs between cesarean section and natural delivery, and to provide reference for controlling the increase of hospital delivery costs. METHODS: The data of inpatient delivery in the Hunan Maternal and Child Health Care Hospital from January 2016 to December 2020 were selected to compare the total inpatient costs and average daily costs of cesarean section and natural delivery. The linear trend model was used to analyze the trend change of inpatient delivery costs and the generalized linear model was used to analyze the influential factors for inpatient delivery costs. RESULTS: The average hospitalization costs of cesarean section (10 447.25 yuan) were higher than that of natural delivery (5 567.95 yuan), and the average daily costs of cesarean section (1 902.57 yuan) were higher than those of natural delivery (1 666.40 yuan). There was no significant increase or decrease in trend for cesarean section, while the average annual growth rate of the costs of natural delivery was 11.79%. The main factors affecting the hospitalization costs of cesarean section and natural delivery included age, occupation, medical insurance, route of admission, length of stay, premature delivery and complications (all P<0.05). CONCLUSIONS: The total hospitalization costs and average daily costs of cesarean section are higher than those of natural delivery, but the costs of natural delivery show a faster growth trend, and the hospitalization costs of cesarean section and natural delivery should be controlled by targeted measures.

[A cross-sectional study on the prevalence rate and influencing factors of non-alcoholic fatty liver disease in overweight/obese children]. / è¶ é‡/è‚¥èƒ–å„¿ç«¥éžé ’ç²¾æ€§è„‚è‚ªè‚ç— æ‚£ç— çŽ‡åŠå ¶å½±å“å› ç´ çš„æ¨ªæ–­é¢ç ”ç©¶.

OBJECTIVES: To investigate the prevalence rate of non-alcoholic fatty liver disease (NAFLD) in overweight/obese children who visit a hospital, and to explore the influencing factors of NAFLD, in order to provide a basis for the prevention of NAFLD in overweight/obese children. METHODS: Overweight/obese children who visited Hunan Children's Hospital from June 2019 to September 2021 were recruited. The prevalence rate of NAFLD was examined. Logistic regression analysis was used to explore the factors influencing the development of NAFLD [non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH)]. Receiver operating characteristic curve analysis was used to evaluate the predictive value of the influencing factors for NAFL and NASH. RESULTS: A total of 844 overweight/obese children aged 6-17 years were enrolled. The prevalence rate of NAFLD in overweight/obese children was 38.2% (322/844), among which the prevalence rates of NAFL and NASH were 28.8% (243/844) and 9.4% (79/844), respectively. Multivariate logistic regression analysis showed that the increase of waist-to-hip ratio (WHR) and low high-density lipoprotein cholesterol (HDL-C) were associated with the development of NAFL and NASH (P<0.05). The receiver operating characteristic curve analysis showed that the combined measurement of WHR and HDL-C had a predictive value for NAFL (area under the curve: 0.653, 95%CI: 0.613-0.694), and for NASH (area under the curve: 0.771, 95%CI: 0.723-0.819). CONCLUSIONS: The prevalence rate of NAFLD in overweight/obese children who visit a hospital is high. WHR and HDL-C are associated with the development of NAFLD and the combined measurement of WHR and HDL-C has a certain value for predicating the development of NAFLD.

Association of insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD in obese children. / èƒ°å²›ç´ ä¿¡å·é€šè·¯ç›¸å ³åŸºå› å¤šæ€æ€§å’ŒåŸºå› -åŸºå› äº¤äº’ä½œç”¨ä¸Žè‚¥èƒ–å„¿ç«¥MAFLDçš„å ³è”.

OBJECTIVES: Insulin signaling pathway plays an important role in metabolic associated fatty liver disease (MAFLD), however, the association between polymorphisms of genes related to insulin signaling pathway and MAFLD remains unclear. This study aims to investigate the association between insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD susceptibility in obese children so as to provide scientific basis for further study of genetic mechanism. METHODS: A total of 502 obese children with MAFLD who admitted to Hunan Provincial Children's Hospital from September 2019 to October 2021, were recruited as a case group, and 421 obese children with non-MAFLD admitted during the same period were recruited as a control group. Socio-demographic information, preterm birth history, eating habits, and exercise status of the subjects were collected by inquiry survey, and anthropometric information was collected by physical measurement. At the same time, 2 mL of venous blood was collected to extract DNA, and the polymorphism of insulin signaling pathway-related genes (5 representative candidate genes, 12 variants) was detected. Multivariate Logistic regression analysis was used to investigate the association between insulin signaling pathway-related gene polymorphisms and MAFLD in obese children. RESULTS: After adjusting for confounder factors, INS rs3842748 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 1.749 (1.053 to 2.905), 1.909 (1.115 to 3.267), 1.862 (1.098 to 3.157), all P<0.05]; INS rs3842752 was significantly associated with the risk of MAFLD in obese children in heterozygous and dominant models [OR and 95% CI 1.736 (1.028 to 2.932), 1.700 (1.015 to 2.846), all P<0.05]. NR1H3 rs3758674 was significantly correlated with the risk of MAFLD in obese children in allele model [OR and 95% CI 0.716 (0.514 to 0.997), P<0.05]. SREBP-1c rs2297508 was significantly associated with the risk of MAFLD in obese children in allele and dominant models [OR and 95% CI 0.772 (0.602 to 0.991) and 0.743 (0.557 to 0.991), all P<0.05]. SREBP-1c rs8066560 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 0.759 (0.589 to 0.980), 0.733 (0.541 to 0.992), 0.727 (0.543 to 0.974), all P<0.05]. NR1H3 rs3758674 mutant C and SREBP-1c rs2297508 mutant G had interaction in the development of MAFLD in obese children [OR and 95% CI 0.407 (0.173 to 0.954), P<0.05]. CONCLUSIONS: The INS, NR1H3, and SREBP-1c gene polymorphisms in the insulin signaling pathway are associated with the susceptibility of MAFLD in obese children, but the functions and mechanisms of these genes need to be further studied.

Weight-Control Behaviors and Dietary Intake in Chinese Adults: An Analysis of Three National Surveys (2002-2015).

Weight control through dietary management is becoming increasingly common worldwide. This study aimed to evaluate and compare the dietary intake and diet quality between Chinese adults with and without weight-control behaviors. Data were collected from the China National Nutrition Survey 2002, 2012, and 2015. Dietary intake was assessed using a combination of 24 h dietary recall of three consecutive days and a weighing method. Diet quality was calculated based on China healthy diet index (CHDI). A total of 167,355 subjects were included, of which 11,906 (8.0%) adults reported attempting to control weight within the past 12 months. Participants with weight control had lower daily total energy intake, as well as lower percentages of energy from carbohydrates, low-quality carbohydrates, and plant protein, but higher percentages of energy from protein, fat, high-quality carbohydrates, animal protein, saturated fatty acids, and monounsaturated fatty acids than those without weight control. Additionally, the CHDI score in the weight-control group was higher than those without (53.40 vs. 48.79, p < 0.001). Fewer than 40% of participants in both groups met the requirement for all specific food groups. Chinese adults who reported weight-control behaviors had an energy-restricted diet characterized by reduced carbohydrate intake and overall higher diet quality compared with those without dietary-control behaviors. However, both groups had significant room for improvement in meeting dietary recommendations.

Identifying the Novel Gut Microbial Metabolite Contributing to Metabolic Syndrome in Children Based on Integrative Analyses of Microbiome-Metabolome Signatures.

The pathogenesis of gut microbiota and their metabolites in the development of metabolic syndrome (MS) remains unclear. This study aimed to evaluate the signatures of gut microbiota and metabolites as well as their functions in obese children with MS. A case-control study was conducted based on 23 MS children and 31 obese controls. The gut microbiome and metabolome were measured using 16S rRNA gene amplicon sequencing and liquid chromatography-mass spectrometry. An integrative analysis was conducted, combining the results of the gut microbiome and metabolome with extensive clinical indicators. The biological functions of the candidate microbial metabolites were validated in vitro. We identified 9 microbiota and 26 metabolites that were significantly different from the MS and the control group. The clinical indicators of MS were correlated with the altered microbiota Lachnoclostridium, Dialister, and Bacteroides, as well as with the altered metabolites all-trans-13,14-dihydroretinol, DL-dipalmitoylphosphatidylcholine (DPPC), LPC 24: 1, PC (14:1e/10:0), and 4-phenyl-3-buten-2-one, etc. The association network analysis further identified three MS-linked metabolites, including all-trans-13,14-dihydroretinol, DPPC, and 4-phenyl-3-buten-2-one, that were significantly correlated with the altered microbiota. Bio-functional validation showed that all-trans-13, 14-dihydroretinol could significantly upregulate the expression of lipid synthesis genes and inflammatory genes. This study identified a new biomarker that may contribute to MS development. These findings provided new insights regarding the development of efficient therapeutic strategies for MS. IMPORTANCE Metabolic syndrome (MS) has become a health concern worldwide. Gut microbiota and metabolites play an important role in human health. We first endeavored to comprehensively analyze the microbiome and metabolome signatures in obese children and found the novel microbial metabolites in MS. We further validated the biological functions of the metabolites in vitro and illustrated the effects of the microbial metabolites on lipid synthesis and inflammation. The microbial metabolite all-trans-13, 14-dihydroretinol may be a new biomarker in the pathogenesis of MS, especially in obese children. These findings were not available in previous studies, and they provide new insights regarding the management of metabolic syndrome.

Successful administration of low-dose almonertinib in a patient with lung adenocarcinoma after osimertinib-induced interstitial lung disease: a case report and literature review.

Osimertinib, the third generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the standard treatment for nonsmall cell lung cancer with EGFR mutation. However, osimertinib-induced interstitial lung disease (OsiILD) is considered to be a serious adverse event, so some patients will have to discontinue the use of osimertinib due to OsiILD. Almonertinib is a novel third-generation EGFR-TKI. We herein report a patient who developed OsiILD after the use of osimertinib and then switched to almonertinib for further treatment with success. This is the first report of a successfull rechallenge with low-dose almonertinib after OsiILD. We also reviewed the literature to explore the possible risk factors and the subsequent treatment of OsiILD, suggesting that low-dose almonertinib may be an option for follow-up treatment of OsiILD.

Biodegradation of MC-LR and its key bioactive moiety Adda by Sphingopyxis sp. YF1: Comprehensive elucidation of the mechanisms and pathways.

Microcystins (MCs) are harmful to the ecology and public health. Some bacteria can degrade MCs into Adda, but few can destroy Adda. Adda is the key bioactive moiety of MCs and mainly contributes to hepatotoxicity. We had previously isolated an indigenous novel bacterial strain named Sphingopyxis sp. YF1 that can efficiently degrade MCs and its key bioactive moiety Adda, but the mechanisms remained unknown. Here, the biodegradation mechanisms and pathways of Adda were systematically investigated using multi-omics analysis, mass spectrometry and heterologous expression. The transcriptomic and metabolomic profiles of strain YF1 during Adda degradation were revealed for the first time. Multi-omics analyses suggested that the fatty acid degradation pathway was enriched. Specifically, the expression of genes encoding aminotransferase, beta oxidation (ß-oxidation) enzymes and phenylacetic acid (PAA) degradation enzymes were significantly up-regulated during Adda degradation. These enzymes were further proven to play important roles in the biodegradation of Adda. Simultaneously, some novel potential degradation products of Adda were identified successfully, including 7­methoxy-4,6-dimethyl-8-phenyloca-2,4-dienoic acid (C17H22O3), 2-methyl-3­methoxy-4-phenylbutyric acid (C12H16O3) and phenylacetic acid (PAA, C8H8O2). In summary, the Adda was converted into PAA through aminotransferase and ß-oxidation enzymes, then the PAA was further degraded by PAA degradation enzymes, and finally to CO2 via the tricarboxylic acid cycle. This study comprehensively elucidated the novel MC-LR biodegradation mechanisms, especially the new enzymatic pathway of Adda degradation. These findings provide a new perspective on the applications of microbes in the MCs polluted environment.

Association between inflammatory markers and non-alcoholic fatty liver disease in obese children.

Background: Given the high prevalence of non-alcoholic fatty liver disease (NAFLD) in obese children, non-invasive markers of disease to date are still limited and worth exploring. Objective: This study aimed to evaluate the association between inflammatory markers and NAFLD in obese children. Methods: We performed a case-control study in Hunan Children's Hospital from September 2020 to September 2021. Study participants were children with obesity diagnosed with NAFLD by abdominal ultrasound examination. Mean platelet volume (MPV), platelet distribution width (PDW), neutrophil, lymphocyte, monocyte, and platelet counts were extracted from medical records and inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression analysis was performed to evaluate the association between inflammatory markers and NAFLD. We also used receiver operating characteristic curve analysis to assess the discriminative ability of inflammatory cytokines for NAFLD. Results: Two hundred and sixty-seven obese children were enrolled, including 176 NAFLD patients and 91 simple obesity controls. Multivariable logistic model indicated that increased interleukin (IL)-1ß [odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.04-1.27], IL-6 (OR = 1.28, 95% CI: 1.07-1.53), and IL-17 (OR = 1.04, 95% CI: 1.02-1.07) levels were significantly associated with NAFLD. In contrast, we observed non-significant associations for IL-8, IL-12, IL-21, IL-32, tumor necrosis factor-α (TNF-α), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), mean platelet volume (MPV), and platelet distribution width (PDW) with NAFLD. The area under the curves (AUCs) of IL-1ß, IL-6, and IL-17 to discriminate obese children with or without NAFLD were 0.94, 0.94, and 0.97, respectively. Conclusions: Our results indicated that IL-1ß, IL-6, and IL-17 levels were significantly associated with NAFLD. These inflammatory cytokines may serve as non-invasive markers to determine the development of NAFLD and potentially identify additional avenues for therapeutic intervention.

Self-Reported Dietary Management Behaviors and Dietary Intake among Chinese Adults with Diabetes: A Population-Based Study.

Few studies have analyzed the implementation of dietary management in Chinese adults with diabetes. Thus, we assessed and compared dietary intake and diet quality between diabetic patients with and without dietary management behaviors (DPDM vs. NDPDM), and evaluated the adherence to dietary guidelines in both groups of patients. The data were obtained from the 2002, 2010-2013, and 2015 China National Nutrition Survey. A total of 69,583, 67,177, and 96,631 subjects participated in the 2002, 2010-2013, and 2015 survey rounds, respectively. The dietary intake data were measured using 3-day 24 h dietary recalls and weighed records of household condiments. The China Healthy Diet Index (CHDI) was used to evaluate diet quality. The study included 6229 patients with diabetes, of which 78% had dietary management behaviors. The diabetic patients with dietary management behaviors showed higher percentages of energy from high-quality carbohydrates, animal protein, saturated fatty acids, and unsaturated fatty acids and lower percentages from low-quality carbohydrates and plant protein than NDPDM. The diabetic patients with dietary management behaviors also had lower intakes of cereals and tubers and higher intakes of vegetables than NDPDM. The total CHDI score of DPDM was higher than NDPDM (56.3 ± 12.7 vs. 54.1 ± 12.3). The proportion of DPDM meeting the recommended intake for different food items ranged from 3.3% to 42.8% and from 3.0% to 39.2% in NDPDM. The diabetic patients with dietary management behaviors showed better adherence to dietary guidelines and higher diet quality scores than NDPDM, while the overall adherence was poor in both groups of patients. Our findings suggested that measures are needed to promote and refine dietary management behaviors, which can help to improve disease management in diabetic patients.

The Association Between Severity of Anemia During Pregnancy and Severe Maternal Outcomes: A Retrospective Cohort Study.

Purpose: Anemia is a worldwide common condition during pregnancy, conferring a number of health risks to mothers. However, very little is known about the association between severity of anemia and severe maternal outcomes. This study aimed to assess the association between severity of anemia during pregnancy and the risk of severe maternal outcomes. Patients and Methods: This retrospective cohort study was based on data from China's National Maternal Near Miss Surveillance System for the period 2017-2018, which included 18 hospitals in southern China. Pregnant women admitted for delivery were divided into 4 groups based on severity of anemia during pregnancy: no anemia, mild anemia, moderate anemia, and severe anemia groups. Severe maternal outcomes were a composite of life-threatening conditions (ie, organ dysfunction) as defined by the WHO criteria, occurring at any time after admission until discharge or death. Modified Poisson regression analyses and propensity score-weighted regression analyses were used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) of severe maternal outcomes among women with anemia of varying severity during pregnancy. Results: The incidence of severe maternal outcomes was 0.3% (417/138,556) in total, and the rates were 0.1% (85/99,755), 0.2% (30/18,502), 1.2% (234/19,697) and 11.3% (68/602) in no anemia, mild anemia, moderate anemia and severe anemia group, respectively. Compared with no anemia, the adjusted RR for severe maternal outcomes was 4.19 (95% CI, 3.20-5.50) in moderate anemia group and 22.12 (95% CI, 15.43-31.69) in severe anemia group; the weighted RR was 1.01 (95% CI, 1.01-1.01) in moderate anemia group and 1.11 (95% CI, 1.07-1.14) in severe anemia group. Conclusion: Moderate to severe anemia during pregnancy was independently associated with an increased risk of severe maternal outcomes. Maternal health care providers and pregnant women themselves should give more attention to the prevention and treatment of anemia during pregnancy, especially moderate to severe anemia.

Cervical cancer prognosis and related risk factors for patients with cervical cancer: a long-term retrospective cohort study.

This study aims to explore the recurrence rate and overall survival for patients with cervical cancer after the first treatment and the related risk factors. A retrospective cohort study was conducted on cervical cancer patients enrolled in a cancer specialist hospital in Hunan Province, China from January 1992 to December 2005 and followed up until December 2010. Kaplan-Meier survival analysis was used to estimate the cumulative recurrence rate, and Cox proportional hazards model was utilized to identify risk factors associated with prognosis. A total of 4358 patients were enrolled with a median follow-up of 7.4 years (range 5-19 years), and 372 (8.5%) patients had cancer recurrence. The cumulative recurrence rate showed a rapid increase from 3.8% in the first year after discharge to 8.0% in the fifth year, and the recurrence rate remained relatively stable afterward reaching 9.7% and 10.8% in the 10th and the 15th year, respectively. The median time to recurrence was 15.5 months with an IQR of 5.5-40.0 months. The Cox regression showed that miscarriage, clinical stage, and treatment received were significantly associated with cervical cancer recurrence after adjustment for confounders. Patients with recurrence showed a significantly higher risk for mortality than those without recurrence (HR 2.79, 95% CI 2.42-3.22). This study depicted the long-term recurrence rate and survival after recurrence for patients with cervical cancer after the first treatment, and reported time to recurrence and risk factors related to recurrence. These findings may provide important evidence for designing targeted interventions for the treatment of cervical cancer.

Association of Inflammatory Cytokines With Non-Alcoholic Fatty Liver Disease.

Background: Inflammatory cytokines have been considered to be significant factors contributing to the development and progression of non-alcoholic fatty liver disease (NAFLD). However, the role of inflammatory cytokines in NAFLD remains inconclusive. Objective: This study aimed to evaluate the association between inflammatory cytokines and NAFLD. Methods: PubMed, Web of Science, the Cochrane Library, and EMBASE databases were searched until 31 December 2021 to identify eligible studies that reported the association of inflammatory cytokine with NAFLD and its subtypes. We pooled odds ratios (ORs) and hazard risk (HRs) with 95% confidence intervals (CIs) and conducted heterogeneity tests. Sensitivity analysis and analysis for publication bias were also carried out. Results: The search in the databases identified 51 relevant studies that investigated the association between 19 different inflammatory cytokines and NAFLD based on 36,074 patients and 47,052 controls. The results of the meta-analysis showed significant associations for C-reactive protein (CRP), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) with NAFLD (ORs of 1.41, 1.08, 1.50, 1.15 and 2.17, respectively). In contrast, we observed non-significant associations for interferon-γ (IFN-γ), insulin-like growth factor (IGF-II), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-7 (IL-7), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-12 (IL-12), monocyte chemoattractant protein-1(MCP-1), and transforming growth factor-ß (TGF-ß) with NAFLD. Our results also showed that CRP, IL-1ß, and TNF-α were significantly associated with non-alcoholic steatohepatitis (NASH) and hepatic fibrosis. Conclusions: Our results indicated that increased CRP, IL-1ß, IL-6, TNF-α, and ICAM-1 concentrations were significantly associated with increased risks of NAFLD. These inflammatory mediators may serve as biomarkers for NAFLD subjects and expect to provide new insights into the aetiology of NAFLD as well as early diagnosis and intervention.