ObjectiveTo investigate the contamination status of ochratoxin A (OTA) in commercially available food products in Shanghai, and to assess OTA exposure levels and the associated non-carcinogenic and carcinogenic risks among pregnant women by integrating dietary consumption data of this population. MethodsThe levels of OTA contamination in 1 520 food samples collected in Shanghai from 2022 to 2023 were determined using liquid chromatography-tandem mass spectrometry. An exposure assessment model was developed based on the dietary consumption levels of pregnant women from the 2016‒2017 Shanghai Pregnant Women Dietary Monitoring Survey to calculate the estimated daily intake (EDI) of OTA, the margin of exposure for non-carcinogenic toxicity (MOE₁), and the margin of exposure for carcinogenic toxicity (MOE₂). An MOE₁ greater than 200 and an MOE₂ greater than 10 000 indicate that the non-carcinogenic toxicity and carcinogenic toxicity resulting from exposure are negligible, respectively. For samples with OTA contamination levels below the limit of detection (LOD), which accounted for more than 80% of the samples, the OTA levels were assigned values of 0 and LOD, respectively, for subsequent calculations. ResultsThe detection rates of OTA in cereals, nuts, dried fruits, and alcohol samples collected in 2022 were 2.03%, 0, 0, and 0, respectively. The OTA detection rates in cereals, nuts, dried fruits, beans, and alcohol samples collected in 2023 were 2.50%, 0.39%, 2.47%, 1.67%, and 13.33%, respectively. For pregnant women in Shanghai in 2022, simulation results indicated that when assigning a value of 0 and the LOD, theP₅₀ values of EDI for dietary OTA exposure were 0.05 and 0.72 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.25 and 2.40 ng·(kg·d)^-1, respectively. For pregnant women in Shanghai in 2023, the P₅₀ values of EDI for dietary OTA exposure were 0.04 and 1.00 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.23 and 2.67 ng·(kg·d)^-1, respectively, both substantially below the tolerable daily intake (TDI) for OTA [17 ng·(kg·d)^-1]. The EDI for dietary OTA exposure in 100.0% of Shanghai pregnant women was lower than the TDI, indicating an overall low level of dietary OTA exposure among this population. For 100.0% of pregnant women, the MOE₁ for dietary OTA exposure exceeded 200. When assigned a value of 0, the MOE₂ for 100.0% of pregnant women in both 2022 and 2023 exceeded10 000. When assigned the LOD value, 72.3% and 81.8% of pregnant women in 2022 and 2023, respectively, had an MOE₂ exceeding 10 000. ConclusionFrom 2022 to 2023, samples of cereals, nuts, dried fruits, beans, and alcohol sold in Shanghai exhibited varying degrees of OTA contamination. The overall EDI of OTA exposure among pregnant women in Shanghai remained at a low level. The non-carcinogenic and carcinogenic risks associated with OTA exposure were generally low and at controllable levels.

Emerging mycotoxins are mycotoxins that have emerged in recent years, encompassing more than ten different families of mycotoxins, primarily Alternaria toxins (ATs), enniatins (ENNs), and beauvericin (BEA). These contaminants are widely found in a variety of food groups including cereals, fruits and vegetables, beer, wine, beans, and potatoes. Studies have shown that multiple physiological toxicities of the emerging mycotoxins are identified in plants, animals, and various human cell lines, and their presence are associated with certain human diseases. Notably, the emerging mycotoxins are not only prevalent in food but also frequently detected in human biological samples (e.g., serum, urine, and breast milk). Furthermore, multiple risk assessment studies have indicated that dietary exposure to the emerging mycotoxins, particularly ATs, exceed safe levels in some populations, posing potential threats to both food safety and human health. This article reviewed the contamination and physiological toxicity of three major emerging mycotoxins—ATs, ENNs, and BEA—in food, as well as research progress in human exposure assessment by different risk evaluation methods (e.g., dietary contamination & intake assessment and human biomonitoring). Additionally, it discussed current research challenges and unresolved scientific issues, aiming to provide insights for the biological control of emerging mycotoxins in food and the assessment of their exposure risks in human populations.

Background Deoxynivalenol (DON), a priority contaminant for food safety risk monitoring, is produced by Fusarium spp. infesting crops, and its common derivatives are 3-acetyl-DON (3A-DON) and 15-acetyl-DON (15A-DON), which have been shown to possess gastrointestinal toxicity, immunotoxicity, reproductive toxicity, and cytotoxicity. Due to the stable physicochemical properties of the DON family of toxins (DONs), they cannot be effectively removed during food processing, thus following the food chain, entering the human body, and posing health risks. Objective To understand the contamination status of DONs in commercial foods (cereals and bakery products) in Shanghai in 2022–2023, and to assess the exposure risk of DONs in pregnant women by combining their dietary consumption data. Methods Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to determine the contamination level of DONs in 1 100 food samples (cereals and baked goods) collected in 2022 and 944 samples collected in 2023 from Shanghai. The dietary monitoring data of pregnant women in Shanghai from 2016 to 2017 were adopted. The monitoring employed the food frequency questionnaire distributed among pregnant women through a combination of online telephone enquiry and offline on-site face-to-face survey to estimate their food consumption levels. An exposure assessment model was established to calculate the exposure level to DONs, and the probability distribution of the DONs exposure level in the pregnant women group in Shanghai was obtained by applying @Risk 7.5 software and simulating the calculation according to the Monte Carlo principle. With reference to the tolerable daily intake (TDI) of DONs [1.00 µg·(kg·d)⁻¹] proposed by the Joint FAO/WHO Expert Committee on Food Additives, the risk of exposure to DONs from commercial cereals and bakery products in pregnant women in Shanghai was assessed. Results DONs were detected in cereal and bakery samples collected in 2022 and 2023 with different levels of contamination. The level of DONs in cereal foods in 2023 (mean: 36.33 µg·kg⁻¹) decreased compared to 2022 (mean: 23.64 µg·kg⁻¹). However, the positive rate (71.67%) and level (mean: 51.22 µg·kg⁻¹) of DONs in bakery products increased significantly compared with 2022 (positive rate: 10.00%, mean: 24.39 µg·kg⁻¹). The mean consumption of cereals in 783 pregnant women was 222.48 g·d⁻¹ and the mean consumption of bakery products was 36.07 g·d⁻¹, and there was no statistically significant difference in the intake of all types of cereals and bakery products across the early, middle, and late stages of pregnancy. The modelled intakes of DONs via commercial cereals and bakery products for pregnant women in Shanghai were calculated to be 0.20 and 0.57 µg·(kg·d)⁻¹ in 2022 for the mean level and the 95th percentile level, respectively, and 0.16 µg·(kg·d)⁻¹ and 0.35 µg·(kg·d)⁻¹ in 2023, respectively. The results of the health risk assessment showed that pregnant women in Shanghai had 2.6% and 1.4% probability of exposure to DONs from cereal consumption in 2022 and 2023, respectively. Conclusion The risk of exposure of pregnant women in Shanghai to DONs via commercial cereals and bakery products is relatively low (1.4%-2.6%). However, considering the physical sensitivity of pregnant women, they should avoid consuming moldy grains and appropriately reduce intake of bakery products.

Objective:To investigate the association between adiponectin-related copy number variation (CNV) region (CNVR) and gestational diabetes mellitus (GDM).Methods:Pregnant women who had prenatal screening in Anqing Municipal Hospital, Anhui Province, from February 2018 to December 2020 were surveyed for baseline information collection, and blood samples were collected. The outcome information was obtained by post pregnancy follow-up. Latex-enhanced immunoturbidimetry and ASA-CHIA chip were used to detect serum adiponectin levels and CNV of pregnant women, respectively. After genotyping, CNV data were processed with software PennCNV 1.0.5 following standard quality control procedure. CNVR were identified and integrated by using software R 4.3.3. Then the associations between CNVR and adiponectin was evaluated, and gene annotation and over-representation analysis were conducted. The log-binomial regression model was used to adjust relevant covariates and analyze the association between adiponectin-related CNVR and GDM.Results:The detection rate of GDM was 9.54% (176/1 845) in the pregnant women. The genotyping information of 1 840 people (99.73%) passed quality evaluation. A total of 33 878 CNVs were identified, and 1 449 CNVRs were obtained after integration. After the false discovery rate method correction, CNVR_132 (CHR2: 47611743-47635062), CNVR_254 (CHR3: 10182703-10183872), CNVR_691 (CHR7: 150637053-150834539) and CNVR_1101 (CHR14: 104248431-104830620) were correlated with adiponectin levels (all P<0.05). Over- representation analysis showed that the molecular function of ribonucleotide binding [Gene Ontology (GO): 0032553] was significantly enriched based on the GO database. The log-binomial regression model, adjusting age, pre-pregnancy BMI, history of miscarriage, smoking history, and family history of diabetes, indicated that CNVR_132 (CHR2: 47611743-47635062) and CNVR_1101 (CHR14: 104248431-104830620) were not statistically associated with the risk for GDM (both P>0.05). However, CNVR_254 (CHR3: 10182703-10183872, a RR=1.83, 95% CI: 1.15-2.91) and CNVR_691 (CHR7: 150637053-150834539, a RR=1.73, 95% CI: 1.23-2.43) might be associated with an increased risk for GDM (all P<0.05). Conclusion:Adiponectin-related CNVR_254 (CHR3: 10182703-10183872) and CNVR_691 (CHR7: 150637053-150834539) might be risk factors for the incidence of GDM.

Objective:To investigate the association between adiponectin-related copy number variation (CNV) region (CNVR) and gestational diabetes mellitus (GDM).Methods:Pregnant women who had prenatal screening in Anqing Municipal Hospital, Anhui Province, from February 2018 to December 2020 were surveyed for baseline information collection, and blood samples were collected. The outcome information was obtained by post pregnancy follow-up. Latex-enhanced immunoturbidimetry and ASA-CHIA chip were used to detect serum adiponectin levels and CNV of pregnant women, respectively. After genotyping, CNV data were processed with software PennCNV 1.0.5 following standard quality control procedure. CNVR were identified and integrated by using software R 4.3.3. Then the associations between CNVR and adiponectin was evaluated, and gene annotation and over-representation analysis were conducted. The log-binomial regression model was used to adjust relevant covariates and analyze the association between adiponectin-related CNVR and GDM.Results:The detection rate of GDM was 9.54% (176/1 845) in the pregnant women. The genotyping information of 1 840 people (99.73%) passed quality evaluation. A total of 33 878 CNVs were identified, and 1 449 CNVRs were obtained after integration. After the false discovery rate method correction, CNVR_132 (CHR2: 47611743-47635062), CNVR_254 (CHR3: 10182703-10183872), CNVR_691 (CHR7: 150637053-150834539) and CNVR_1101 (CHR14: 104248431-104830620) were correlated with adiponectin levels (all P<0.05). Over- representation analysis showed that the molecular function of ribonucleotide binding [Gene Ontology (GO): 0032553] was significantly enriched based on the GO database. The log-binomial regression model, adjusting age, pre-pregnancy BMI, history of miscarriage, smoking history, and family history of diabetes, indicated that CNVR_132 (CHR2: 47611743-47635062) and CNVR_1101 (CHR14: 104248431-104830620) were not statistically associated with the risk for GDM (both P>0.05). However, CNVR_254 (CHR3: 10182703-10183872, a RR=1.83, 95% CI: 1.15-2.91) and CNVR_691 (CHR7: 150637053-150834539, a RR=1.73, 95% CI: 1.23-2.43) might be associated with an increased risk for GDM (all P<0.05). Conclusion:Adiponectin-related CNVR_254 (CHR3: 10182703-10183872) and CNVR_691 (CHR7: 150637053-150834539) might be risk factors for the incidence of GDM.

Objective:To investigate the relationship between retinoblastoma binding protein 1 (RB1) gene deletion and the prognosis of multiple myeloma (MM) patients, and the possible effect of renal insufficiency on it.Methods:A retrospective cohort study was conducted. The clinical data and follow-up information of MM patients who were treated in the Second Affiliated Hospital of Xuzhou Medical University and the Affiliated Hospital of Xuzhou Medical University from December 2020 to November 2023 were collected. According to the presence of RB1 gene deletion in bone marrow samples detected by fluorescence in situ hybridization (FISH), the patients were divided into the RB1 gene deletion group and the RB1 gene non-deletion group, and the clinicopathological characteristics and hematological index levels were compared between the two groups. Renal insufficiency was determined by renal function assessment indicator serum creatinine (Scr) >177 μmol/L. The Spearman test was used to analyze the relationship between the number of RB1 gene deletion positive cells and levels of Scr, hemoglobin and serum calcium in MM patients. The Kaplan-Meier method was used to analyze progression-free survival (PFS), and the Cox proportional hazards model was used to determine the influencing factors of PFS in all MM patients and RB1 gene deletion and non-deletion MM patients.Results:A total of 75 MM patients were enrolled, of whom 24 (32.0%) had RB1 gene deletion. There were no significant differences in gender, age ≥65 years old, bone destruction and lactate dehydrogenase level between the RB1 gene deletion and non-deletion groups (all P > 0.05). There were significant differences in the distributions of patients in each stage of MM International Staging System (ISS) and revised International Staging System (R-ISS) between the two groups, as well as in hemoglobin, serum calcium, Scr, β 2-microglobulin, serum albumin levels, and the proportion of bone marrow plasma cells (all P < 0.05). The number of RB1 gene deletion positive cells was positively correlated with Scr level ( r = 0.863, P = 0.016), but not with hemoglobin and serum calcium levels (both P > 0.05). The PFS of the RB1 gene non-deletion group was better than that of the RB1 gene deletion group (1-year PFS rate: 83.5% vs. 71.7%, 2-year PFS rate: 56.3% vs. 26.3%), and the difference was statistically significant ( P = 0.012). PFS in the non-renal insufficiency group was better than that in the renal insufficiency group (1-year PFS rate: 85.6% vs. 61.9%, 2-year PFS rate: 58.0% vs. 13.5%), and the difference was statistically significant ( P = 0.001). The PFS of patients without renal insufficiency in both the RB1 gene deletion and non-deletion groups was better than that in patients with renal insufficiency, and the differences were statistically significant (both P < 0.05). Multivariate Cox regression analysis showed that ISS stage Ⅲ was an independent risk factor for poor PFS in MM patients (stage Ⅲ vs. stage Ⅰ, HR = 11.317, 95% CI: 1.220-104.979, P = 0.033). Multivariate Cox regression analysis in RB1 gene deletion and non-deletion groups showed that ISS stage Ⅲ (stage Ⅲ vs. stageⅠ, HR = 4.166, 95% CI: 1.419-12.225, P = 0.009), R-ISS stage Ⅲ (stage Ⅲ vs. stage Ⅰ, HR = 3.800, 95% CI: 1.005-14.367, P = 0.049), serum calcium > 2.52 mmol/L (> 2.52 mmol/L vs. ≤2.52 mmol/L, HR = 2.398, 95% CI: 1.037-5.546, P = 0.041) and renal insufficiency (yes vs. no, HR = 2.363, 95% CI: 1.021-5.472, P = 0.045) were independent risk factors for poor PFS in RB1 gene non-deletion MM patients, and serum calcium >2.52 mmol/L (>2.52 mmol/L vs. ≤ 2.52 mmol/L, HR = 3.673, 95% CI: 1.160-11.627, P = 0.027) and renal insufficiency (yes vs. no, HR = 3.985, 95% CI: 1.220-13.016, P = 0.022) were independent risk factors for poor PFS in RB1 gene deletion MM patients. Conclusions:The PFS of MM patients with RB1 gene deletion is worse than that of patients without RB1 gene deletion, RB1 gene deletion may be related to renal insufficiency in MM patients, and the prognosis of MM patients with RB1 gene deletion and renal insufficiency may be worse.

Objective:To investigate the relationship between retinoblastoma binding protein 1 (RB1) gene deletion and the prognosis of multiple myeloma (MM) patients, and the possible effect of renal insufficiency on it.Methods:A retrospective cohort study was conducted. The clinical data and follow-up information of MM patients who were treated in the Second Affiliated Hospital of Xuzhou Medical University and the Affiliated Hospital of Xuzhou Medical University from December 2020 to November 2023 were collected. According to the presence of RB1 gene deletion in bone marrow samples detected by fluorescence in situ hybridization (FISH), the patients were divided into the RB1 gene deletion group and the RB1 gene non-deletion group, and the clinicopathological characteristics and hematological index levels were compared between the two groups. Renal insufficiency was determined by renal function assessment indicator serum creatinine (Scr) >177 μmol/L. The Spearman test was used to analyze the relationship between the number of RB1 gene deletion positive cells and levels of Scr, hemoglobin and serum calcium in MM patients. The Kaplan-Meier method was used to analyze progression-free survival (PFS), and the Cox proportional hazards model was used to determine the influencing factors of PFS in all MM patients and RB1 gene deletion and non-deletion MM patients.Results:A total of 75 MM patients were enrolled, of whom 24 (32.0%) had RB1 gene deletion. There were no significant differences in gender, age ≥65 years old, bone destruction and lactate dehydrogenase level between the RB1 gene deletion and non-deletion groups (all P > 0.05). There were significant differences in the distributions of patients in each stage of MM International Staging System (ISS) and revised International Staging System (R-ISS) between the two groups, as well as in hemoglobin, serum calcium, Scr, β 2-microglobulin, serum albumin levels, and the proportion of bone marrow plasma cells (all P < 0.05). The number of RB1 gene deletion positive cells was positively correlated with Scr level ( r = 0.863, P = 0.016), but not with hemoglobin and serum calcium levels (both P > 0.05). The PFS of the RB1 gene non-deletion group was better than that of the RB1 gene deletion group (1-year PFS rate: 83.5% vs. 71.7%, 2-year PFS rate: 56.3% vs. 26.3%), and the difference was statistically significant ( P = 0.012). PFS in the non-renal insufficiency group was better than that in the renal insufficiency group (1-year PFS rate: 85.6% vs. 61.9%, 2-year PFS rate: 58.0% vs. 13.5%), and the difference was statistically significant ( P = 0.001). The PFS of patients without renal insufficiency in both the RB1 gene deletion and non-deletion groups was better than that in patients with renal insufficiency, and the differences were statistically significant (both P < 0.05). Multivariate Cox regression analysis showed that ISS stage Ⅲ was an independent risk factor for poor PFS in MM patients (stage Ⅲ vs. stage Ⅰ, HR = 11.317, 95% CI: 1.220-104.979, P = 0.033). Multivariate Cox regression analysis in RB1 gene deletion and non-deletion groups showed that ISS stage Ⅲ (stage Ⅲ vs. stageⅠ, HR = 4.166, 95% CI: 1.419-12.225, P = 0.009), R-ISS stage Ⅲ (stage Ⅲ vs. stage Ⅰ, HR = 3.800, 95% CI: 1.005-14.367, P = 0.049), serum calcium > 2.52 mmol/L (> 2.52 mmol/L vs. ≤2.52 mmol/L, HR = 2.398, 95% CI: 1.037-5.546, P = 0.041) and renal insufficiency (yes vs. no, HR = 2.363, 95% CI: 1.021-5.472, P = 0.045) were independent risk factors for poor PFS in RB1 gene non-deletion MM patients, and serum calcium >2.52 mmol/L (>2.52 mmol/L vs. ≤ 2.52 mmol/L, HR = 3.673, 95% CI: 1.160-11.627, P = 0.027) and renal insufficiency (yes vs. no, HR = 3.985, 95% CI: 1.220-13.016, P = 0.022) were independent risk factors for poor PFS in RB1 gene deletion MM patients. Conclusions:The PFS of MM patients with RB1 gene deletion is worse than that of patients without RB1 gene deletion, RB1 gene deletion may be related to renal insufficiency in MM patients, and the prognosis of MM patients with RB1 gene deletion and renal insufficiency may be worse.

Humans ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Mutation/genetics* ; Colorectal Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/metabolism*

Objective:To evaluate the characteristics of vaginal flora between normal and abnormal pregnant women throughout pregnancy.Methods:Vaginal swab specimens were collected from pregnant women in the first (<14 gestation weeks, GW), second (14~28 GW) and third trimester (>28 GW) in Anqing, Anhui Province from February 2018 to February 2020. Pregnant women were divided into normal and abnormal groups according to all clinical diagnosis. The sequences of 16S rRNA gene (V3-V4) from vaginal swabs were analyzed using QIIME2 platform. The differences in the dominance of Lactobacillus, community state type (CST) transition, Alpha diversity and Beta diversity were analyzed. Diversity data after log transition were used in the analysis of linear mixed model. Results:A total of 34 pregnant women (10 normal and 24 abnormal) with 102 samples were included for analysis. The composition of vaginal flora between two groups: the relative abundance of Lactobacillus was the highest at the genus level and Lactobacillus crispatus and Lactobacillus iners was the top two species with high relative abundance. The dominance of Lactobacillus, Alpha diversity and transition of CST were also similar. Both groups had a gradually decreased trend of Alpha diversity with GW, and the Chao1, Observed species and Faith′s PD indexes′ were different in different GW ( P<0.05). All Beta diversity metrics in normal group had descending trend, with lower value of the index of first distance which implied a higher microbiota stability, while Bray-Curtis, Weighted UniFrac distance had ascending trend in abnormal group, indicating lower stability. Jaccard distance′s first distance was statistically differed among GW and Unweighted UniFrac distance′s differed between normal and abnormal groups. Conclusions:The first distance of Unweighte UniFrac distance in abnormal pregnant women is higher than that of normal pregnant women and the vaginal flora in abnormal group has lower stability.