Characterization of the gut microbiota and fecal and blood metabolomes under various factors in urban children from Northwest China.

Introduction: Children have regional dynamics in the gut microbiota development trajectory. Hitherto, the features and influencing factors of the gut microbiota and fecal and plasma metabolites in children from Northwest China remain unclear. Methods: Shotgun metagenomic sequencing and untargeted metabolomics were performed on 100 healthy volunteers aged 2-12 years. Results: Age, body mass index (BMI), regular physical exercise (RPE), and delivery mode (DM) significantly affect gut microbiota and metabolites. Lactobacillus, Butyricimonas, Prevotella, Alistipes, and predicted pathway propanoate production were significantly increased with age while Bifidobacterium breve, B. animalis, B. pseudocatenulatum, Streptococcus infantis, and carbohydrate degradation were decreased. Fecal metabolome revealed that the metabolism of caffeine, amino acids, and lipid significantly increased with age while galactose metabolism decreased. Noticeably, BMI was positively associated with pathogens including Erysipelatoclostridium ramosum, Parabacteroides distasonis, Ruminococcus gnavus, and amino acid metabolism but negatively associated with beneficial Akkermansia muciniphila, Alistipes finegoldii, Eubacterium ramulus, and caffeine metabolism. RPE has increased probiotic Faecalibacterium prausnitzii and Anaerostipes hadrus, acetate and lactate production, and major nutrient metabolism in gut and plasma, but decreased pathobiont Bilophila wadsworthia, taurine degradation, and pentose phosphate pathway. Interestingly, DM affects the gut microbiota and metabolites throughout the whole childhood. Bifidobacterium animalis, Lactobacillus mucosae, L. ruminis, primary bile acid, and neomycin biosynthesis were enriched in eutocia, while anti-inflammatory Anaerofustis stercorihominis, Agathobaculum butyriciproducens, Collinsella intestinalis, and pathogenic Streptococcus salivarius, Catabacter hongkongensis, and amino acid metabolism were enriched in Cesarean section children. Discussion: Our results provided theoretical and data foundation for the gut microbiota and metabolites in preadolescent children's growth and development in Northwest China.

[Investigation on the recommended dose of prebiotic in health food in China in 1996-2022].

OBJECTIVE: To understand the recommended dose distribution of prebiotic-containing health food in China. METHODS: The overall recommended dose of prebiotic health food was available from the label information of approved prebiotic health food from 1996 to 2022; the recommended dose distribution of prebiotic-containing health food was analyzed from different healthy functions and different ways of addition. RESULTS: There were 174 prebiotic-containing health food products with clear dose information, respectively, involving 5 prebiotics including Fructooligosaccharides, Galactooligosaccharides, Isomaltooligosaccharides, Xylo-oligosaccharides and Polydextrose, and the majority of prebiotics were added in combination, with 159 products. The recommended dose range of prebiotic-containing health food products was wide, and in general, the dose of prebiotic-containing health food products used alone was higher than the dose used in combination. The recommended daily intake range of health food containing Fructooligosaccharides was 5.28-17 500 mg/d, the recommended daily intake range of health food containing Isomaltooligosaccharides was 220-28 000 mg/d, the dose range of health food containing Xylo-oligosaccharides was 8.4-2 800 mg/d, the dose range of health food containing Polydextrose was 4-12 120 mg/d, the number of Galacto-Oligosaccharides products Only two kinds of products were included, with doses of 259.8 mg/d and 3500 mg/d, respectively. The claimed functions of prebiotic health food products were focused on laxative function, immunity enhancement, and regulation of intestinal flora. The application dose of prebiotic health food with different functional compounding additions was close to the overall dose. CONCLUSION: The recommended dosage range of prebiotics in health food containing prebiotics in China is large, and prebiotics in products are mainly added by compounding.

[Effect of high selenium on insulin signaling pathway PI3K-AKT-mTOR in L02 cells].

OBJECTIVE: To observe the effect of high selenium on insulin signaling pathway PI3K-AKT-mTOR in L02 cells. METHODS: One group of L02 cell was treated with different concentrations of selenomethionine(SeMet, 0.001, 0.0025, 0.005, 0.0075, 0.01, 0.025, 0.05, 0.075 and 0.1µmol/L) for 48 h, then cultured with serum-free medium for 4 h and stimulated with 1 µmol/L insulin for 15 min. The insulin signaling pathway(PI3K-AKT-mTOR) was detected by WB. Another group of L02 cell was treated with the same concentrations of SeMet as above for 48 h. The cell supernatant and lysates were collected for the analysis of SELENOP and GPX1, respectively by WB. RESULTS: The expressions of P-AKT-(Ser-473), P-AKT-(Thr-308), PI3K and mTOR in L02 cells under high-Se were decreased with the increase of SeMet concentration. The expressions of GPX1 and SELENOP were enhanced with the increase of SeMet. CONCLUSION: The insulin signaling pathway, PI3K-AKT-mTOR, was damaged in L02 cell under high-Se stress.

In-depth multiomic characterization of the effects of obesity in high-fat diet-fed mice.

High-fat diet (HFD)-fed mice have been widely used in the clinical investigation of obesity. However, the long-term effect of HFD on gut microbiota and metabolites, plasma and liver metabolomics, colonic and liver transcriptomics remain largely unknown. In this study, 6-week-old C57BL/6J male mice fed with HFD for 14 weeks showed increased obesity-related indexes including alanine aminotransferase, aspartate aminotransferase, total cholesterol, total triglyceride, free fatty acids, lipopolysaccharides, IL-6, and TNFα. Furthermore, microbial diversity and richness were also significantly decreased. In the colon, genes involved in tryptophan metabolism, PPAR signaling pathway, cholesterol metabolism, and lipid localization and transport, were upregulated. While in the liver, MAPK signaling and unsaturated fatty acid biosynthesis were upregulated. Metabolomic analyses revealed decreased levels of glycerophospholipids and fatty acyl, but increased amino acids, coenzymes and vitamins, and organic acids in the colon, suggesting high absorption of oxidized lipids, while acyl-carnitine, lysophosphatidylcholine, lysophosphatidylethanolamine, and oxidized lipids were reduced in the liver, suggesting a more active lipid metabolism. Finally, correlation analyses revealed a positive correlation between gut microbiota and metabolites and the expression of genes associated with lipid localization, absorption, and transport in the colon, and nutrients and energy metabolism in the liver. Taken together, our results provide a comprehensive characterization of long-term HFD-induced obesity in mice.

Increased Expression of PHGDH Under High-Selenium Stress In Vivo.

The purpose of this study is to explore the glycolytic remodeling under high-selenium (Se) stress. Three groups of male C57BL/6J mice were fed on diets with different Se contents (0.03, 0.15, and 0.30 mg Se/kg). Glucose tolerance test (GTT) and insulin tolerance test (ITT) were measured at the third month. Mice were killed at the fourth month. Plasma, liver, and muscle tissues were fetched for biochemistry and Se analysis. The expressions of insulin signaling pathway (PI3K-AKT-mTOR), glutathione peroxidase 1 (GPX1), selenoprotein N (SELENON), 3-phosphoglycerate dehydrogenase (PHGDH), serine hydroxymethyltransferases 1 (SHMT1), 5,10-methylenetetrahydrofolate reductase (MTHFR), and methionine synthase (MS) were analyzed by western blotting (WB) in liver and muscle tissues. The results of GTT and ITT showed that glucose tolerance and insulin tolerance were both abnormal in the 0.03 mg Se/kg and 0.3 mg Se/kg groups. Se concentrations in plasma, liver, and muscle of 0.03 mg Se/kg group were significantly lower than that of 0.15 mg Se/kg and 0.30 mg Se/kg groups (p < 0.05 or p < 0.01). The expressions of P-Akt (Thr-308) in muscle (p < 0.05) and PI3K and mTOR in liver (p < 0.001) of 0.30 mg Se/kg group were downregulated. The expressions of GPX1 in liver and muscle (p < 0.05 and p < 0.001), SELENON in muscle (p < 0.05), PHGDH in liver and muscle (p < 0.05), and SHMT1 (p < 0.05), MTHFR (p < 0.001), and MS (p < 0.001) in muscle of 0.3 mg Se/kg group were upregulated. The de novo serine synthesis pathway (SSP) was found to be activated in liver and muscle tissues of mice with a high-Se diet for the first time.

Iodine Excess May Lead to Low Exam Score in Children Aged 8-10 Years.

Recent research has shown that iodine excess may damage children's intelligence. Years of monitoring results in Shanghai show the iodine status has approached the upper limit of the appropriate range for children aged 8-10 years, indicating a risk of iodine excess. We used multi-stage random sampling to select children. Sixteen districts of Shanghai were divided into five units based on geographic location, and one primary school was randomly selected from each unit. In each selected school, about 40 children aged 8-10 years were randomly recruited to measure their urinary iodine concentration (UIC), household salt iodine concentration (SIC), the score of the final unified exam of the last semester, and school canteen salt iodine concentration. The median UIC of 3213 children aged 8-10 years in Shanghai was 195.4 (122.0, 285.8) µg/L and exceeded 200 µg/L in 48.8% of the population. Household and school canteen iodized salt coverage rates were 60.3% and 82.5% respectively, and mean household and school canteen SICs were 21.51 ± 9.30 mg/kg and 25.29 ± 3.40 mg/kg respectively. By correcting for potential confounding factors, logistic regression demonstrated that compared to the adequate iodine status group, students in the slight iodine excess group were less likely to get "A" (score > 90) in math, Chinese, and English exams (Math: OR = 0.775, 95% CI = 0.660-0.911, P = 0.002; Chinese: OR = 0.707, 95% CI = 0.543-0.842, P < 0.001; English: OR = 0.720, 95% CI = 0.610-0.849, P < 0.001). In Shanghai, the iodine status of 8-10-year-old children is approaching the upper limit of the adequate range. Iodine excess in Shanghai may lead to low exam scores for students.

Anoikis Patterns in Cervical Cancer: Identification of Subgroups and Construction of a Novel Risk Model for Predicting Prognosis and Immune Response.

BACKGROUND: Cervical cancer has high morbidity and intratumor heterogeneity. Anoikis, a form of programmed cell death preventing detached cancer cells from readhering, may serve as a potential prognostic signature for cervical cancer. This study aimed to assess the predictive performance of anoikis patterns in cervical cancer prognosis. METHODS: Differentially expressed anoikis-related genes (DEARGs) were identified between normal and cancer samples using data from the Gene Expression Omnibus database with the elucidation of mutation status and bio-function. Novel anoikis molecular subtypes were defined in The Cancer Genome Atlas (TCGA) cohort with consensus clustering analysis. A multigene prognostic signature was constructed through least absolute shrinkage and selection operator (LASSO) Cox analysis with internal and external validation. The nomogram-based survival probability of cervical cancer over 3 and 5 years was predicted and assessed with calibration, receiver operating characteristic, decision curve analysis, and Kaplan-Meier curves. Additionally, mutation, function, and immune analysis were conducted among different risk groups. RESULTS: We identified 77 DEARGs between normal and cervical cancer tissues and explored their mutation status and functions. The TCGA cohort could be categorized into two subtypes based on these genes. Furthermore, seven prognostic signature genes were constructed, and the nomogram involving DEARGs and clinicopathological characteristics showed satisfactory predictive performance. Functional analysis indicated that immune-related genes were enriched, and immune status, as well as sensitivity of chemotherapies and targeting drugs, were correlated with the risk model. CONCLUSIONS: Anoikis patterns play important roles in tumor immunity and can be used to predict the prognosis of cervical cancers.

Multiomics Revealed the Multi-Dimensional Effects of Late Sleep on Gut Microbiota and Metabolites in Children in Northwest China.

Background Sleep plays a pivotal role in children's mental and physical development and has been linked to the gut microbiota in animals and adults. However, the characteristics of the gut microbiota and metabolites and the relationship to late bedtimes in children remain unclear. Methods In total, 88 eligible children, aged from 3 to 8 years, were recruited and divided into two groups according to the bedtime collected by designed questionnaires (early, before 22:00: n = 48; late, after 22:00, n = 40). Stools and plasma samples were collected to examine the characteristics of the gut microbiota and metabolites by shotgun metagenomics and metabolomics. Results The richness and diversity of the gut microbiota in children with early bedtime were significantly increased compared with the late ones. Coprococcus, Collinsella, Akkermansia muciniphila, and Bifidobacterium adolescentis were significantly more abundant in children with early bedtime, while Bacteroides and Clostridium sp. CAG-253 were obviously enriched in the late ones. A total of 106 metabolic pathways, including biosynthesis of ribonucleotide, peptidoglycan, and amino acids, and starch degradation were enriched in children with early bedtime, while 42 pathways were abundant in those with late bedtime. Notably, more gut microbial metabolites were observed in children with late bedtime, which included aldehyde, ketones, esters, amino acids and their metabolites, benzene and substituted derivatives, bile acids, heterocyclic compounds, nucleotide and metabolites, organic acid and derivatives, sugars and acyl carnitine. In plasma, fatty amides, lipids, amino acids, metabolites, hormones, and related compounds were enriched in children with early bedtime, while bile acids were higher in children with late bedtime. Association studies revealed that the different microbial species were correlated with metabolites from gut microbiota and plasma. Conclusions The results of our study revealed that the gut microbiota diversity and richness, and metabolic pathways were significantly extensive in children with early bedtime, whereas the gut microbial metabolites were significantly decreased, which might be related to gut microbial differences.

[Comparative study on the essential composition content of commercial infant formula with the requirements in the new national food safety standard in China from 2017 to 2022].

OBJECTIVE: In order to understand the distribution of the essential nutrients content in commercial infant formula in China, and to compare its conformity with the new national standard(GB 10765-2021). METHODS: A total of 477 infant fomulas with production data from January 2017 to June 2022 were collected in China. Information in the product labels was recorded and the distribution of nutrient contents was analyzed, compare with the national food safety standard. RESULTS: Compared with GB 10765-2010, the new standard had 12 essential nutrients content revised, and 10 of which had lower limit values adjusted and 5 of which had upper limit values adjusted. Both the lower and upper limits were increased for three items, including vitamin D, choline and selenium. Compared with the newly revised 12 essential nutrients in the national food safety standard, the coincidence rate of 3 items was 100%, and the coincidence rate of 3 items was more than 80%. The coincidence rate of the actual content of essential nutrients in some products was low, the reason was that they did not meet the lower limit requirements of the new national standard, for example, the non-coincidence rate of vitamin D was as high as 99.79%. In addition, the national food safety standard adjusts choline from an selectable nutrient to an essential one, and the proportion of choline added to commercial products was 84.7%. CONCLUSION: The change of the content of essential nutrients in the new standard has little influence on the products sold in our country. There are a few essential nutrient in the products on the market that need to be adjusted to raise the nutrient level.

[Comparative study on the essential composition content of commercial follow-up formula for young children with the requirements in the new national food safety standard in China from 2017 to 2022].

OBJECTIVE: To understand the distribution of the essential composition content of commercial follow-up formula for young children in China, to analyze the differences with the new requirements of national food safety standard, and to promote the implementation of the new national standard(GB 10767-2021). METHODS: The label information on the total of 483 follow-up formula for young children permitted from January 2017 to June 2022 were collected and recorded, the distribution of essential compositions were analyzed and compared with the new national food safety standard. RESULTS: Compared with GB 10767-2010, 23 essential compositions were revised in the new national standard, 2 new essential compositions, α-linolenic acid and carbohydrates, were required, and 8 minimum requirements and 4 maximum requirements were revised, 16 new maximum requirements were developed. The whole change of the new standard was major. Comparing with GB 10767-2021, there were 8 essential compositions in commercial products with 100% compliance rate and 9 with more than 95% compliance rate, the discordance rate of pantothenic acid, folic acid, vitamin C and Vitamin D was more than 20%, Vitamin D has the highest discordance rate 97.10%. CONCLUSION: Although the revision of the essential composition requirements in the new national standard is major, the compliance rate of almost essential compositions is high. A few of individual essential compositions in some commercial products cannot meet the new standards requirements, the main reason is those can not reach the increased new minimum requirements, especially on vitamin D.

[Investigation on the addition of dietary fiber in infant and follow-up formula in China from 2017 to 2022].

OBJECTIVE: To investigate the addition of dietary fiber in infant formula approved in recent 5 years. METHODS: A total of 1438 infant formula milk powder approved in China from January 2017 to June 2022 were collected and the addition rate, content and mixture of dietary fiber components such as galactooligosaccharide(FOS), fructooligosaccharide(GOS), polyfructose, polyglucose, raffinose and yeast ß-dextran were statistically analyzed. RESULTS: Among the 1438 infant formulas, 84.07%(1209) were added with dietary fiber, and the addition rate increased yearly. Among them, the addition rate of GOS(79.82%) and FOS(79.74%) was the highest, and the median amount of dietary fiber components was 3.00 g/100 g. Among the products added with various dietary fiber components, there were 762 products added with GOS and FOS, The addition ratios of GOS and FOS were mainly concentrated at 1∶1. CONCLUSION: The addition rate of dietary fiber in infant formula milk powder in China is constantly increasing, however there are large differences in the addition amount, dietary fiber combination and proportion of different products.

[Distribution of vitamin K_2 content in Chinese traditional fermented soybean products].

OBJECTIVE: To determine the content of vitamin K_2 in different types of fermented bean products and analyze the difference of vitamin K_(2 )content. METHODS: A total of 98 kinds of typical fermented bean products were included in Chinese traditional fermented bean products(Douchi, Sufu, soybean paste). Process, region, sales volume, raw materials and flavor were considered, and the content of vitamin K_2 in fermented bean products was determined by high performance liquid chromatography. RESULTS: Chinese bean fermented foods generally contained vitamin K_2, and the subtype menaquinone-7(MK-7)was the main one. The content of vitamin K_2 in Douchi was the highest(437.55 µg/100 g), the content of vitamin K_2 in Sufu and Soybean paste were lower(7.48 µg/100 g and 2.47 µg/100 g). The content of vitamin K_2 in bacterial Douchi was higher than that in Mucor type and Aspergillus oryzae type which were 403.94, 232.98 and 81.00 µg/100 g(P<0.05). Soybean type Douchi was higher than that in black bean type of Douchi which were 610.41, 178.08 µg/100 g(P<0.05), and the content of vitamin K_2 in dry Douchi was higher than the content of vitamin K_2 in water Douchi which were 1 517.45 µg/100 g, 297.58 µg/100 g(P<0.05). However, there were no significant difference in the content of vitamin K_2 in Soybean paste and Sufu in different types and regions(P > 0.05). CONCLUSION: Vitamin K_2 is widely contained in Chinese fermented bean products, and its content is mainly affected by fermentation microorganisms and processing technology.

[Staple food habits on glycemic response: a controlled feeding trial].

OBJECTIVE: To study the effects of staple food on the glycemic responses through a controlled feeding trial. METHODS: In November 2020, two groups of volunteers with different staple food habits(the rice group, n=35, and the wheat group, n=35), were recruited from Changzhi Medical College in Shanxi Province. They were subjected to a two-stage feeding trial, in which their staple food habits were maintained in the first stage(staple food fortification period, 4 weeks) and then swapped in the second stage(staple food swap period, 4 weeks), while keeping the rest of the dietary components same. A continuous glucose monitoring system was used to monitor the glycemic response of glucose, steamed buns and steamed rice, equivalent to 50 g of available carbohydrate(CHO). Blood glucose level up to 120 minutes postprandial, incremental area under the curve(iAUC) and glycemic index(GI) were analyzed. RESULTS: During the staple food fortification period, the glycemic response to steamed buns at 15 min(5.43±0.69 vs.5.14±0.50 mmol/L, P=0.047), 30 min(6.63±0.98 vs.6.10±0.70 mmol/L, P=0.012), 45 min(6.81±1.15 vs.6.21±0.67 mmol/L, P=0.011) and 60 min postprandial(6.03±0.96 vs.5.56±0.59 mmol/L, P=0.017) in the rice group were higher than the wheat group, and the trends for blood glucose fluctuation during the 120 minutes after consuming steamed buns were different between the two groups. During the staple food swap period, the 120 min iAUC(83.24±30.15 vs.69.32±26.25 mmol·min/L, P=0.032) and GI(88±24 vs.75±33, P=0.041) of the rice group to steamed buns were higher than the wheat group. Comparing the differences between the two groups in the staple food exchange period and the staple food intensification period, the rice group had an increased glycemic response to steamed buns(P=0.007), while the wheat group had an increased glycemic response to glucose(P<0.001), steamed buns(P<0.001) and steamed rice(P=0.018). The 120 min iAUC of steamed buns in the rice group increased(83.24±30.15 vs.70.12±26.02 mmol·min/L, P=0.029), and the 120 min iAUC of rice in the wheat group(69.75±32.32 vs.54.87±20.43 mmol·min/L, P=0.040) increased. CONCLUSION: Even to the same food, there are significant differences in the glycemic responses of people with different staple food habits, and short-term changes in the intake of staple food will lead to differences in the glycemic response.

[Comparative study on the essential composition content of commercial follow-up formula for older infant with the requirements in the new national food safety standard in China from 2017 to 2022].

OBJECTIVE: To understand the distribution of the content range of essential ingredients in commercial follow-up formula for older infants in China, analyze the differences between the content of essential ingredients in commercial older infant formula milk powder in China and the requirements of the new national standard(GB 10766-2021). METHODS: The label information of 478 commercial follow-up formula for older infant registered and approved from January 2017 to June 2022 were collected and entered. The distribution of essential ingredients was statistically analyzed, which was compared with the requirements of the new national food safety standard. RESULTS: The new national standard has 31 essential components. Compared with the old national standard(GB 10767-2010), five indicators of carbohydrate, α-linolenic acid, choline, selenium and manganese were added. The new national standard has 28 essential component requirements revised, including 13 adjusted the lower limit, 7 adjusted the upper limit, and 16 essential components added the upper limit. Among the approved 478 older infant formula milk powders, the distribution of 11 essential ingredients were all in line with the new national standard, and 14 essential ingredients were less than the lower limit of the new national standard. The essential ingredients whose minimum value was less than the lower limit of the new national standard and the proportion exceeds 50% were vitamin D, iodine and choline. with the proportions(number of cases) of 98.33%(470 cases), 74.06%(354 cases) and 72.37%(275 cases), respectively. The maximum value of essential ingredients exceeded the maximum requirements stipulated in the new national standard, and the protein in 13.18%(63 cases) of the older infant formula milk powder was higher than the maximum requirements of the new national standard. CONCLUSION: The content of essential components in most commercial products in China meets the new national standard requirements. Some essential ingredients need to be adjusted.

[Investigation on the addition of microbial food cultures in infant and follow-up formula in China from 2017 to 2022].

OBJECTIVE: To understand the addition of microbial food cultures in infant and follow-up formula milk powder in China. METHODS: The product information of infant and follow-up formula milk powder approved in China from 2017 to 2022 was investigated, including the query platform and packaging label information, and the strains, addition rates and addition amount of microbial food cultures were statistically analyzed. RESULTS: From 2017 to 2022, a total of 1438 infant and follow-up formula milk powder products were approved in China, of which 434 products were added with microbial food cultures, 6 types of strains were used, namely Bifidobacterium animalis Bb-12, Bifidobacterium lactis HN019, Bifidobacterium lactis Bi-07, Lactobacillus fermentum CECT5716, Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM, the top three addition rates were Bifidobacterium animalis Bb-12, Bifidobacterium lactis HN019 and Bifidobacterium lactis Bi-07, the addition rate were 79.72%, 18.43% and 12.67%, respectively. The addition amount of the strains ranged from 1×10~6 to 6×10~7 CFU/g, the median value was 1×10~6 CFU/g. CONCLUSION: There is insufficient scientific evidence on the feeding effect, types and amounts of microbial food cultures added to infant and follow-up formula in China.

Impacts of ovarian preservation on the prognosis of neuroendocrine cervical carcinoma: a retrospective analysis based on machine learning.

BACKGROUND: Neuroendocrine cervical carcinoma (NECC) is a rare but aggressive malignancy with younger patients compared to other common histology types. This study aimed to evaluate the impacts of ovarian preservation (OP) on the prognosis of NECC through machine learning. METHODS: Between 2013 and 2021, 116 NECC patients with a median age of 46 years received OP or bilateral salpingo-oophorectomy (BSO) and were enrolled in a retrospective analysis with a median follow-up of 41 months. The prognosis was estimated using Kaplan-Meier analysis. Random forest, LASSO, stepwise, and optimum subset prognostic models were constructed in training cohort (randomly selected 70 patients) and tested in 46 patients through receiver operator curves. Risk factors for ovarian metastasis were identified through univariate and multivariate regression analyses. All data processing was carried out in R 4.2.0 software. RESULTS: Among 116 patients, 30 (25.9%) received OP and showed no significantly different OS compared with BSO group (p = 0.072) and got better DFS (p = 0.038). After construction of machine learning models, the safety of OP was validated in lower prognostic risk group (p > 0.05). In patients ≤ 46 years, no impacts of OP were shown for DFS (p = 0.58) or OS (p = 0.67), and OP had no impact on DFS in different relapse risk population (p > 0.05). In BSO group, regression analyses showed that later stage, para-aortic LNM, and parametrial involvement were associated with ovarian metastasis (p < 0.05). CONCLUSIONS: Preserving ovaries had no significant impact on prognosis in patients with NECC. OP should be considered cautiously in patients with ovarian metastasis risk factors.

Analysis of Metabolite Distribution in Rat Liver of High-Fat Model by Mass Spectrometry Imaging.

Hyperlipidemia is a medical condition characterized by elevated levels of blood lipids, especially triglycerides (TG). However, it remains unclear whether TG levels remain consistently elevated throughout the entire developmental stage of the high-lipid state. In our animal experiment, we found that TG levels were significantly higher in the early stage of the high-lipid model but significantly decreased at the 14th week of the late stage, reaching levels similar to those of the control group. This suggests that TG levels in the high-lipid model are not always higher than those of the control group. To determine the reason for this observation, we used in situ mass spectrometry imaging (MSI) to detect the distribution of metabolites in the liver of rats. The metabolite distribution of the control rats at different stages was significantly different from that of the model rats, and the high-lipid model differed significantly from the control rats. We identified nine functional metabolites that showed differences throughout the period, namely, PA(20:3-OH/i-21:0), PA(20:4-OH/22:6), PG(20:5-OH/i-16:0), PG(22:6-2OH/i-13:0), PG(O-18:0/20:4), PGP(18:3-OH/i-12:0), PGP(PGJ2/i-15:0), SM(d18:0/18:1-2OH), and TG(14:0/14:0/16:0), among which TG was most significantly correlated with hyperlipidemia and high lipid. This study is unique in that it used MSI to reveal the changes in metabolites in situ, showing the distribution of different metabolites or the same metabolite in liver tissue. The findings highlight the importance of considering the animal's age when using TG as a biomarker for hyperlipidemia. Additionally, the MSI images of the liver in the high-lipid model clearly indicated the distribution and differences of more significant metabolites, providing valuable data for further research into new biomarkers and mechanisms of hyperlipidemia. This new pathway of in situ, visualized, and data-rich metabolomics research provides a more comprehensive understanding of the characteristics of high lipid and its implications for disease prevention and treatment.

Bifidobacterium as a Potential Biomarker of Sarcopenia in Elderly Women.

Gut microbial dysbiosis influences the development of sarcopenia. This case-control study explored the gut microbiota composition in elderly Chinese women with sarcopenia. The information from 50 cases and 50 controls was collected. Grip strength, body weight, body mass index, skeletal muscle mass, energy intake, and total and high-quality protein intake were lower in cases than in controls (p < 0.05). Gut microbiota metagenomic sequencing showed that phylum Bacteroides was significantly reduced in the case group, whereas genus Prevotella was more abundant (p < 0.05). Linear discriminant analysis (LDA) effect size showed that 9 and 13 distinct microbial taxa were enriched in the case and control groups, respectively (LDA > 2, p < 0.05), among which Prevotella copri and Bifidobacterium longum were significantly different (LDA > 4, p < 0.05). The AUC of Bifidobacterium longum was 0.674 (95% CI: 0.539-0.756). Elderly women with sarcopenia exhibited significantly different gut microbiota compositions than healthy controls.

[Study of high selenium interfering with glucose and one-carbon metabolism in hepatocytes in vitro].

OBJECTIVE: To investigate the effects of high selenium environment on the expression of selenoproteins and enzymes related to glucose and one-carbon metabolism in normal human hepatocytes. METHODS: Ten different concentrations of selenomethionine(SeMet, 0, 0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 5 and 10 µmol/L) was added into the normal human hepatocyts and incubated for 48 hours. The expressions of selenoprotein(GPX1 and SELENOP1) and metabolic enzymes(PHGDH, SHMT1, MTHFR and MS) were analyzed by Western blot. RESULTS: When the concentration of SeMet was 0-10 µmol/L, the expression trend of selenoprotein(GPX1 and SELENOP1) is similar, which first increases and then decreases. There is a slight difference between the inflection points of GPX1 and SELENOP1, which are respectively 0.5 µmol/L and 0.1 µmol/L. The expression trend of serine de novo synthesis pathway key enzymes(PHGDH) and folate cycle metabolizing enzymes(SHMT1, MTHFR and MS) is similar to that of selenoproteins, which also increases first and then decreases, but the inflection points are different, which are respectively 0.1 µmol/L(PHGDH and SHMT1) and 0.01 µmol/L(MTHFR and MS). CONCLUSION: Under the high selenium environment, the glycolytic bypass-serine de novo synthesis pathway is activated to synthesize endogenous serine due to the insufficient intracellular serine supply, causing abnormal glucose metabolism, which is an important extension to the hypothesis of the molecular mechanism of high selenium causing IR.

[Intervention study to inhibit the glucose metabolic remodeling in hepatocytes induced by high-selenium in vitro].

OBJECTIVE: To observe the effect of exogenous serine or glycine on the synthesis of selenoprotein and endogenous serine and the expression of metabolic enzymes in hepatocytes cultured with high-selenium in vitro and its dose-response relationship. METHODS: The experiment was divided into two parts, namely a inhibition experiment and a dose-response experiment, using L02 cells as the intervention target. In the inhibition experiment, the blank control group, high-Se(SeMet) group, serine intervention group and high-Se+serine intervention group were set up. Both SeMet and serine were given at a level of 0.05 µmol/L, and the blank control group was given the same volumes of saline. In the dose-response experiment, the concentration of SeMet was 0.05 µmol/L, and the intervention concentration gradients of serine or glycine were 0, 0.05, 0.1, 0.5, 1, 5, 10, 50, 100 and 500 µmol/L. The expression of phosphoglycerate dehydrogenase(PHGDH)、serine hydroxymethyltransferase 1(SHMT1)、methylenetetrahydrofolate reductase(MTHFR)、selenoprotein P(SELENOP) and glutathione peroxidase 1(GPX1)was detected by Western Blot(WB). RESULTS: (1)In the inhibition experiment, compared with the blank control group, the expression of selenium proteins(GPX1 and SELENOP) in L02 cells of the other three groups were significantly increased(P<0.05). Compared with the high expression of PHGDH in L02 cells of high-Se group, the expressions of PHGDH, SHMT1 and MTHFR in high-Se + serine group were significantly decreased(P<0.05). (2) In the dose-response experiment, the expression of PHGDH enzyme in L02 cells gradually decreased with the increase of the concentration of exogenous serine or glycine, showing an obvious dose-dependent effect. In contrast, none of the other metabolic enzymes(SHMT1 and MTHFR) showed similar trends in protein expression. CONCLUSION: The upregulated expression of PHGDH, the key enzyme in the de novo synthesis pathway of serine in hepatocytes cultured with high-selenium can be inhibited feedback by exogenous serine or endogenous serine transformed from exogenous glycine directly.