ObjectiveThis study aims to explore the potential of different orders of magnitude single-nucleotide polymorphism (SNP) locus combinations for predicting distant kinship relationships. A high-density SNP locus set was constructed, and a comprehensive assessment of its inference capability was conducted. MethodsFirstly, we selected three commercial chip panels, CGA (Chinese genotyping array, Illumina), GSA (Global screening array, Illumina), Affy (23MF_V2 high-density SNP array, Affymetrix) and merged them after quality control, forming a high-density SNP locus panel(1 180 k). Secondly, we selected 161 samples and collected their peripheral blood samples by using whole-genome sequencing technology. Within this sample population, the levels of kinship relationships fully covered the range from level 1 to level 9, and the number of kinship pairs at each level was consistently maintained at over 50 pairs. From 161 samples data of whole-genome sequencing, the 1 180 k locus set was extracted, which is referred to as the high-density SNP locus set in the following text. The kinship inference was conducted using the identity-by-descent (IBD) algorithm with the selected optimal parameters. To comprehensively evaluate the performance of the high-density SNP locus set in kinship inference, we compared it with the three commercial chip panels, the intersection of these three chip loci, and the control sets constructed by randomly reducing the number of the high-density SNP locus set. Based on the changes in the IBD lengths, as well as the dynamic trends in prediction accuracy, we conducted a scientific assessment of the kinship inference capability of the high-density SNP locus set. ResultsAfter screening, a set of 1 184 334 autosomal SNPs was obtained. During the process of screening the optimal IBD length threshold, the result revealed that 0 cM, 1 cM, and 2 cM all demonstrated good applicability. However, to avoid the issue of a large amount of redundant information caused by setting a too low IBD length threshold, this study ultimately selected 2 cM as the optimal threshold. Compared with the average results of three chip panels, the high-density SNP locus set increased the total IBD length and the average IBD length across levels 1-9; the accuracy of the confidence interval for level 8 was 70.97%, which represented a 3.50% improvement; the average confidence interval accuracy for levels 1-8 was 91.39%, representing a 1.00% increase; and the false negative rates at levels 8 and 9 were reduced by 2.42% and 6.76%, respectively. The system efficacy of the high-density SNP locus set for kinship inference of first to eighth degree relationships reached 98.91%. Through random reduction of the high-density SNP locus set results, it is found that increasing the number of SNPs with the panel, the detection efficiency of IBD length showed a significant upward trend. At the same time, the overall trend in the accuracy of kinship relationship prediction as well as the confidence interval accuracy also indicated that both metrics steadily increased with the addition of more loci. ConclusionThe results show that the high-density SNPs panel significantly enhances the efficacy of distant kinship inference, accurately covering kinship degrees, with the average confidence interval accuracy for first to eighth degree relationships stably above 90%. The study finds that increasing the number of SNPs panel can improve the ability to predict distant kinship.

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.

Eucommiae Cortex, the dried bark of Eucommia ulmoides( Eucommiaceae), has both medicinal and edible values.Modern research has shown that Eucommiae Cortex contains various components such as flavonoids, lignans, iridoids, phenolic acids,terpenoids, and steroids, which have anti-osteoporosis, antioxidant, anti-inflammatory, blood glucose-lowering, and gastrointestinal tract-protecting effects. Eucommiae Cortex has applications in multiple fields such as healthcare, industry, and animal husbandry,demonstrating broad development prospects. This article reviews the chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex. Furthermore, according to the concept of quality marker(Q-marker), this article predicts the Q-markers of Eucommiae Cortex from traditional medicinal properties, traditional medicinal effects, new medicinal effects, measurability of chemical components, compatibility, harvesting periods, and geographical origins. The components such as pinoresinol diglucoside,chlorogenic acid, caffeic acid, quercetin, baicalein, baicalin, olivil, coniferyl ferulate, and kaempferol can be used as Q-markers for Eucommiae Cortex, which provide reference for establishing a systematic quality control system for Eucommiae Cortex.
Eucommiaceae/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Quality Control ; Humans ; Animals

Many triterpenoid compounds have been successfully heterologously synthesized in Saccharomyces cerevisiae. To increase the yield of triterpenoids, various metabolic engineering strategies have been developed. One commonly applied strategy is to enhance the supply of precursors, which has been widely used by researchers. Squalene, as a precursor to triterpenoid biosynthesis, plays a crucial role in the synthesis of these compounds. This study primarily investigates the effect of different squalene levels in chassis strains on the synthesis of triterpenoids(oleanolic acid and ursolic acid), and the underlying mechanisms are further explored using real-time quantitative PCR(qPCR) analysis. The results demonstrate that the chassis strain CB-9-5, which produces high levels of squalene, inhibits the synthesis of oleanolic acid and ursolic acid. In contrast, chassis strains with moderate to low squalene production, such as Y8-1 and CNPK, are more conducive to the synthesis of oleanolic acid and ursolic acid. The qPCR analysis reveals that the expression levels of ERG1, βAS, and CrCYP716A154 in the oleanolic acid-producing strain CB-OA are significantly lower than those in the control strains C-OA and Y-OA, suggesting that high squalene production in the chassis strains suppresses the transcription of certain genes, leading to a reduced yield of triterpenoids. Our findings indicate that when constructing S. cerevisiae strains for triterpenoid production, chassis strains with high squalene content may suppress the expression of certain genes, ultimately lowering their production, whereas chassis strains with moderate squalene levels are more favorable for triterpenoid biosynthesis.
Squalene/analysis* ; Saccharomyces cerevisiae/genetics* ; Triterpenes/metabolism* ; Metabolic Engineering ; Oleanolic Acid/biosynthesis* ; Ursolic Acid

The differences in chemical quality characteristics between Xinjiang Rehmannia glutinosa and R. glutinosa were analyzed to provide a theoretical basis for the introduction and quality control of R. glutinosa. In this study, the high performance liquid chromatography(HPLC) fingerprints of 6 batches of Xinjiang R. glutinosa and 10 batches of R. glutinosa samples were established. The content of iridoid glycosides, phenylethanoid glycosides, monosaccharides, oligosaccharides, and polysaccharides in Xinjiang R. glutinosa and R. glutinosa was determined by high performance liquid chromatography-diode array detection(HPLC-DAD), high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD), and ultraviolet-visible spectroscopy(UV-Vis). The determination results were analyzed with by chemical pattern recognition and entropy weight TOPSIS method. The results showed that there were 19 common peaks in the HPLC fingerprints of the 16 batches of R. glutinosa, and catalpol, aucubin, rehmannioside D, rehmannioside A, hydroxytyrosol, leonuride, salidroside, cistanoside A, and verbascoside were identified. Hierarchical cluster analysis(HCA) and principal component analysis(PCA) showed that Qinyang R. glutinosa, Mengzhou R. glutinosa, and Xinjiang R. glutinosa were grouped into three different categories, and eight common components causing the chemical quality difference between Xinjiang R. glutinosa and R. glutinosa in Mengzhou and Qinyang of Henan province were screened out by orthogonal partial least squares discriminant analysis(OPLS-DA). The results of content determination showed that there were glucose, sucrose, raffinose, stachyose, polysaccharides, and nine glycosides in Xinjiang R. glutinosa and R. glutinosa samples, and the content of catalpol, rehmannioside A, leonuride, cistanoside A, verbascoside, sucrose, and glucose was significantly different between Xinjiang R. glutinosa and R. glutinosa. The analysis with entropy weight TOPSIS method showed that the comprehensive quality of R. glutinosa in Mengzhou and Qinyang of Henan province was better than that of Xinjiang R. glutinosa. In conclusion, the types of main chemical components of R. glutinosa and Xinjiang R. glutinosa were the same, but their content was different. The chemical quality of R. glutinosa was better than Xinjiang R. glutinosa, and other components in R. glutinosa from two producing areas and their effects need further study.
Rehmannia/classification* ; Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Quality Control

OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Imaging examination is a crucial part in diagnosis and treatment of central nervous system infection(CNSI),involving complex imaging sequences and parameters.This consensus was jointly written by multiple CNSI imaging experts in China,aimed to standardize imaging examination of CNSI.

Objective:To investigate the short-term clinical efficacy of implantation with a 3D-printed microporous titanium prosthesis in the treatment of large segmental infectious tibial defects.Methods:A retrospective analysis was conducted of the electronic medical records of the 47 patients with large segmental tibial defects who had been treated with 3D-printed microporous titanium prostheses at Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force from January 2019 to February 2024. The cohort included 36 males and 11 females, with an age of (46.2±11.8) years and a mean bone defect length of 12.3 (8.0, 16.8) cm. In the 19 patients complicated with soft tissue defects, the area of soft tissue defects ranged from 10.0 cm × 6.0 cm to 33.0 cm × 10.0 cm. For the 28 patients without soft tissue defects at the lower leg, the bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage; for the 19 patients complicated with soft tissue defects, the soft tissue defects at the lower limb were repaired using an anterolateral thigh flap with vascular anastomosis at the same time when bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage. After infection control at 2 to 8 months after surgery, individualized 3D-printed microporous titanium prostheses were implanted at the second stage to reconstruct the bone defects. Postoperative observations included the patients' first standing time, crutch walking time, full weight-bearing time, osseointegration of the tibial fracture and the prosthesis, and complications during follow-up.Results:The follow-up period for the 47 patients was (34.7±14.3) months. The first standing time was (2.2±0.6) months, crutch walking time (3.8±1.1) months, and full weight-bearing time (5.3±1.2) for this cohort. The evaluation by the Paley's bone healing score resulted in 25 excellent cases, 18 good cases, 1 medium case, and 3 poor cases, giving an excellent and good rate of 91.5% (43/47). One year after operation, the X-ray films showed that the tibial fractures and prostheses were well integrated in the 43 patients. Two patients developed recurrent tibial infection which was responded to replacement of the vancomycin-loaded calcium sulfate spacer. The fixation screws for tibial prosthesis were broken in one patient, but no recurrence of infection was observed after revision. The overall incidence of complications was 6.4% (3/47).Conclusion:In the treatment of large segmental infectious tibial defects, by facilitating rapid functional recovery and ensuring a low incidence of complications, implantation with a 3D-printed microporous titanium prosthesis demonstrates fine short-term clinical efficacy.